The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. The risk of myocardial infarction associated with antihypertensive drug therapies. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Effect of beta-blockers on the mortality of Japanese patients with myocardial infarction. Mortality benefit of beta-blockade after successful elective percutaneous coronary intervention. Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). 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Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction. Should nephrologists use beta-blockers? A perspective. STOP-Hypertension--preliminary communication from the pilot study of the Swedish Trial in Old Patients with Hypertension. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group. 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Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial: rationale and design of a multicenter, randomized, placebo-controlled, clinical trial of metoprolol for patients with diabetes mellitus who are undergoing major noncardiac surgery. Rationale, design, and organization of the PeriOperative ISchemic Evaluation (POISE) trial: a randomized controlled trial of metoprolol versus placebo in patients undergoing noncardiac surgery. Beta-blocker use is associated with improved outcomes in adult burn patients. Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency. 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The International Prospective Primary Prevention Study in Hypertension (IPPPSH): Objectives and methods Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension–2 The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Effects of renin-angiotensin blockers/inhibitors and statins on mortality and functional impairment in polypathological patients. Cardiac 123I-MIBG imaging and clinical variables in risk stratification in patients with heart failure treated with beta blockers A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives South African hypertension guideline 2011. 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Beta blockers in heart failure: a comparison of a vasodilating beta blocker with metoprolol. Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Role of High-Dose Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction and Elevated Heart Rate. Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study.
OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually OBJECTIVE To assess the association between  first myocardial infa rct ion and the use of antihypertensive agents .  DESIGN AND SETTING We conducted a population -based case-control study among enrollees of the Group Health Cooperative of Puget Sound ( GHC ) . PATIENTS AND METHODS Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infa rct ion from 1986 through 1993 among women and from 1989 through 1993 among men . Controls were a stratified r and om sample of hypertensive GHC enrollees , frequency matched to the cases on age , sex , and calendar year . All 623 cases and 2032 controls had pharmacologically treated hypertension . Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors . Antihypertensive therapy was assessed using the GHC 's computerized pharmacy data base . RESULTS The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease . Compared with users of diuretics alone , the adjusted risk ratio of myocardial infa rct ion was increased by about 60 % among users of calcium channel blockers with or without diuretic ( risk ratio = 1.62 % ; 95 % confidence interval [ Cl ] , 1.11 to 2.34 ; P = .01 ) . The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker .  Among these subjects , the use of calcium channel blockers compared with beta-blockers was associated with about a 60 % increase in the adjusted risk of myocardial infa rct ion ( risk ratio = 1.57 ; 95 % Cl , 1.21 to 2.04 ; P < .001 ) . While high doses of beta-blockers were associated with a decreased risk of myocardial infa rct ion ( trend P = .04 ) , high doses of calcium channel blockers were associated with an increased risk ( trend P < .01 ) . CONCLUSIONS In this study of hypertensive patients , the use of short-acting calcium channel blockers , especially in high doses , was associated with an increased risk of myocardial infa rct ion . Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies , including calcium channel blockers , on several important cardiovascular end points . Until these results are available , the findings of this study support the current guidelines from the Joint National Committee on the Detection , Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated , unacceptable , or not tolerated BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death OBJECTIVE The Captopril Prevention Project ( CAPPP ) evaluated the effects of an ACE inhibitor-based therapeutic regimen on  cardiovascular mortality and morbidity in hypertension .  One planned sub analysis of the CAPPP was to evaluate the outcome in the diabetic patient group . RESEARCH DESIGN AND METHODS In the CAPPP , 572 ( 4.9 % of 10,985 hypertensive patients ) had diabetes at baseline and were studied according to a prospect i ve , r and omized , open , blinded , end point trial design . Patients aged 25 - 66 years with diastolic blood pressure > or = 100 mmHg were included and r and omized to receive either captopril or conventional antihypertensive treatment ( diuretics and /or beta-blockers ) . RESULTS The primary end point , fatal and nonfatal myocardial infa rct ion and stroke as well as other cardiovascular deaths , was markedly lower in the captopril than in the conventional therapy group ( relative risk [ RR ] = 0.59 ; P = 0.018 ) . Specifically , cardiovascular mortality , defined as fatal stroke and myocardial infa rct ion , sudden death , and other cardiovascular death , tended to be lower in the captopril group ( RR = 0.48 ; P = 0.084 ) , and no difference was observed between the study groups for stroke ( RR = 1.02 ; P = 0.96 ) . Myocardial infa rct ions were less frequent in the captopril group than in the conventional therapy group ( RR = 0.34 ; P = 0.002 ) . Furthermore , total mortality was lower in the captopril as compared with the conventional therapy group ( RR = 0.54 ; P = 0.034 ) . Patients with impaired metabolic control seemed to benefit the most from ACE inhibitor-based therapy . CONCLUSIONS Captopril is superior to a diuretic/beta-blocker antihypertensive treatment regimen in preventing cardiovascular events in hypertensive diabetic patients , especially in those with metabolic decompensation BACKGROUND After a myocardial infa rct ion , a higher prevalence of coronary vasospastic response has been reported in the Japanese population than in the Caucasian population . Beta-blockers may exacerbate coronary vasospasm . However , beta-blockers are given to Japanese patients after an acute myocardial infa rct ion , though the mortality benefit is unknown . Thus , we investigated the mortality benefit of beta-blockers given to Japanese patients after an acute myocardial infa rct ion . METHODS We prospect ively studied consecutive patients with a first myocardial infa rct ion admitted to the coronary care unit of Kansai Medical University Hospital , Osaka , Japan from May 1994 through the end of 2001 . Patients who died during hospitalization or who were referred for coronary artery bypass graft surgery were excluded . The association of beta-blocker use with mortality after discharge was assessed by a proportional hazards regression analysis . RESULTS There were 546 patients and 400 ( 73.3 % ) patients were treated with beta-blockers  at the time of discharge from hospital . During a mean follow-up of 2 years , 46 ( 8.4 % ) patients died . Beta-blocker therapy was associated with a reduced mortality after adjustment for age , gender , Q wave myocardial infa rct ion , reperfusion therapy during acute phase , Killip functional class , serum creatinine level , cardiovascular risk factors , and medications ( hazard ratio=0.51 , 95 % confidence interval=0.27 to 0.95 ) . CONCLUSIONS Contrary to the concern that beta-blocker therapy might induce coronary vasospasm and reduce survival , beta-blocker therapy improved survival after discharge in Japanese patients with a first myocardial infa rct ion OBJECTIVES The goal of this study was to evaluate the mortality benefit of beta-blockers  after successful percutaneous coronary intervention ( PCI ) . BACKGROUND Beta-blockers reduce mortality after myocardial infa rct ion ( MI ) , though limited data are available regarding their role after successful PCI . METHODS Each year from 1993 through 1999 , the first 1,000 consecutive patients undergoing PCI  were systematic ally followed up . Patients presenting with acute or recent MI , shock , or unsuccessful revascularization procedures were excluded from the analysis . Clinical , procedural , and follow-up data of beta-blocker-treated and non-beta-blocker-treated patients were compared . A multivariate survival analysis model using propensity analysis was used to adjust for heterogeneity between the two groups . RESULTS Of the 4,553 patients , 2,056 ( 45 % ) were treated with beta-blockers at the time of the procedure . Beta-blocker therapy was associated with a mortality reduction from 1.3 % to 0.8 % at 30 days ( p = 0.13 ) and a reduction from 6.0 % to 3.9 % at one year ( p = 0.0014 ) . This survival benefit of beta-blockers was independent of left ventricular function , diabetic status , history of hypertension , or history of MI . Using propensity analysis , beta-blocker therapy remained an independent predictor for one-year survival after PCI ( hazard ratio , 0.63 ; 95 % confidence interval , 0.46 to 0.87 ; p = 0.0054 ) . CONCLUSIONS Within this large prospect i ve registry , beta-blocker use was associated with a marked long-term survival benefit among patients undergoing successful elective percutaneous coronary revascularization A multicenter , r and omized , controlled , double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone , for the long-term management of middle-aged adults with " mild " hypertension . Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population ; mild hypertension 's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall ; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy , and other trials that failed to demonstrate beneficial impact on morbidity and mortality , possibly due to residual questions concerning aspects of benefit to risk ratios with these medications ; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means ; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors , angiotensin converting enzyme inhibitors and calcium channel blockers ; paucity of data from trials on long-term combined effects of diet and drug therapy , and of diet alone , for people with mild hypertension . During the next few years , phase 1 of the trial will study 6 groups of drugs . The step-1 drugs are angiotensin converting enzyme inhibitor ( enalapril ) , alpha 1 inhibitor ( doxazosin ) , beta blocker ( acebutolol ) , calcium channel blocker ( amlodipine ) , diuretic ( chlorthalidone ) and placebo . All participants are to receive vigorous sustained nutritional counseling to reduce obesity , moderate sodium intake and avoid heavy use of alcohol . Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension , side effects ( i.e. , clinical and biochemical ) and consequent need to discontinue drug and quality of life . Phase-1 data are to be used to complete the phase-2 design , with the ultimate aim to assess effects on morbidity and mortality The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infa rct ion ( AMI ) .  Primary percutaneous coronary intervention ( PCI ) , which has become the mainstay of treatment for AMI , is associated with a lower mortality than fibrinolysis . The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear . We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure . The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infa rct ion ( ALPS-AMI ) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infa rct ion . We prospect ively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients ( median age 66 years ; 18.2 % women ) who had Killip class 1 on admission and were discharged alive . The primary endpoint was all-cause mortality . The 3-year follow-up was completed in 413 patients ( 93.0 % ) . During this follow-up , 21 patients ( 4.7 % ) died . In Kaplan – Meier analysis , patients on beta-blockers had a significantly lower incidence of all-cause mortality ( 2.7 vs. 7.3 % , log-rank p = 0.025 ) . After adjusting for the calculated propensity score for using beta-blockers , their use remained an independent predictor of all-cause mortality ( hazard ratio 0.309 ; 95 % confidence interval 0.116–0.824 ; p = 0.019 ) . In the statin era , the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission To collect background data for a prospect i ve clinical trial of beta-blocking agents in the prevention of deaths after stroke , the long-term prognosis in 60 patients discharged from a stroke unit on beta-blocker therapy  was compared with the outcome in 60 matched patients with stroke but without beta-blockers .  Matching included sex , age , type of stroke , and presence or absence of hypertension and cardiac failure . Thirteen patients ( 22 % ) in the beta-blocker group died during a median followup of 41 months . Of the 60 patients not on beta-blockade at discharge , 21 ( 35 % ) died during a median followup of 36 months . By life-table technique and log-rank test , the relative risk for death was 0.60:1.00 ( p = 0.14 ) . During followup , 12 recurrent strokes were observed in patients on beta-blockers and 19 in patients without beta-blockers ( relative risk 0.57:1.00 ; p = 0.12 ) . It appeared that the reduction in mortality could only marginally be ascribed to fewer deaths from myocardial infa rct ion ; other causes of death were also less frequent in beta-blocker-treated patients . The results emphasize that supplementary information on the effect of beta-blocking agents on mortality after stroke is needed before a larger trial of beta-blocker therapy in patients with manifest cerebrovascular disease can be initiated This retrospective , nonr and omized analysis evaluated the effect of initiating statin or beta-blocker treatment early in the course of heart failure developed during acute myocardial infa rct ion compared with the effect of neither or both treatments . Early initiation of statins or beta blockers alone was associated with improved event-free survival , and the benefits of the combined treatment were additive OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually Three hundred and four hypertensive patients with different degrees of left ventricular hypertrophy ( LVH ) were recruited and followed for 4 years . The patients were r and omized into two groups : Group I ( 150 patients ) was treated with a combination of hypotensive drugs including beta-blockers , and group II ( 154 patients ) was treated with the same combination of drugs including diuretics instead of beta-blockers . By the end of the fourth year , 60 endpoints were recorded : 17 strokes , 13 myocardial infa rct ions , and 30 cases of chronic coronary insufficiency . Mortality was statistically higher in group II ( 7 of 154 or 5 % v 1 of 150 or 1 % ) ( P less than .035 ) , but there was no difference between the groups in the incidence of nonfatal endpoints . These data confirm that beta-blockers can reduce mortality associated with the complications presented in hypertensive patients . Increased left ventricular myocardial mass ( greater than 200 g , according to Teichholz ' formula ) was shown to have prognostic value for the development of complications . In patients with LVMM greater than 200 g , the probability of fatal complications was higher ( P less than .007 ) , as was the probability of nonfatal myocardial infa rct ion ( P less than .01 ) , development of coronary artery disease ( P less than .02 ) , and all complications ( P less than .0003 ) . Regression of LVH to less than 200 g ( according to Teichholz ' formula ) improved prognosis We sought to identify the clinical characteristics and outcomes of patients who had advanced heart failure and nonfatal myocardial infa rct ion ( MI ) in the beta-Blocker Evaluation of Survival Trial ( BEST ) and to investigate whether bucindolol alters the risk of developing nonfatal MI . Of the 2,708 patients enrolled in the study , 142 had suspected MI and 69 had confirmed MI ; there were 860 deaths overall . The rate of nonfatal MI in the BEST was low over the 4.1 years of follow-up ( 4.8 % had suspected events and 2.4 % had adjudicated events ) and was similar to that in high-risk population s. Cox 's proportional hazard model with 23 prespecified c and i date variables associated advanced age , heart failure symptoms , male gender , ischemic etiology , diabetes , and hypertension with nonfatal MI or cardiovascular death . The 2-year mortality rate was 56 % for the cohort that had suspected nonfatal MI versus 30 % for the cohort that did not ( p = 0.01 ) . Likewise , the risk of hospitalization for congestive heart failure was twofold greater . Beta-blocker therapy with bucindolol result ed in a 52 % decrease in suspected nonfatal MI ( 2.9 % vs 5.5 % , p = 0.001 ) . In conclusion , nonfatal MI occurs at low rates but increases the risks for mortality and hospitalization in patients who have advanced heart failure . Beta-blocker therapy with bucindolol appears to attenuate the risk of nonfatal MI in this population This study evaluated the effects of propranolol on recovery of heart rate variability ( HRV )  after acute myocardial infa rct ion and its relation to outcome in the Beta-blocker Heart Attack Trial ( BHAT ) . Beta blockers improve mortality after acute myocardial infa rct ion , but through an unknown mechanism . Depressed HRV , a measure of autonomic tone , predicts mortality after acute myocardial infa rct ion . Whether beta blockers influence recovery of HRV after acute myocardial infa rct ion , and thereby improve outcome , is unknown . We compared 24-hour HRV parameters at 1 week after acute myocardial infa rct ion and after 6 weeks of treatment with  propanolol ( n = 88 ) or placebo ( n = 96 ) . The relation between 25-month outcome ( death/acute myocardial infa rct ion/congestive heart failure ) , propranolol treatment , and HRV was further analyzed . After 6 weeks , high-frequency ( HF ) power ( log-normalized ) , an index of vagal tone , increased more in propranolol-treated  patients ( 4.28 + /- 0.1 to 5.17 + /- 0.09 ms(2 ) ) than in placebo-treated patients ( 4.26 + /- 0.09 to 4.77 + /- 0.1 ms(2 ) , p < 0.05 ) . Sympathovagal balance measured by the low-frequency ( LF ) to HF ratio increased in placebo-treated patients ( 3.55 + /- 0.24 to 3.86 + /- 0.24 ) but decreased in those treated with propranolol ( 3.76 + /- 0.29 to 3.17 + /- 0.23 , p < 0.01 ) . Other frequency-domain parameters increased over time but were not affected by propranolol . Propranolol blunted the morning increase in the LF/HF ratio . Recovery of HF , the strongest HRV predictor of outcome , and propranolol therapy independently predicted outcome . In summary , after acute myocardial infa rct ion , propranolol therapy improves recovery of parasympathetic tone , which correlates with improved outcome , and decreases morning sympathetic predominance . These findings may eluci date the mechanisms by which beta blockers decrease mortality and reduce the early morning risk of sudden death after acute myocardial infa rct ion OBJECTIVES To study determinants and adverse outcomes ( mortality and rehospitalization ) of beta-blocker underuse in elderly patients with myocardial infa rct ion ; and whether the relative risks ( RRs ) of survival associated with beta-blocker use were comparable to those reported in the large r and omized controlled trials ( RCTs ) . SETTING New Jersey Medicare population . DESIGN Retrospective cohort design using linked Medicare and drug cl aims data from 1987 to 1992 . PATIENTS Statewide cohort of 5332 elderly 30-day acute myocardial infa rct ion ( AMI ) survivors with prescription drug coverage , of whom 3737 were eligible for beta-blockers .  MAIN OUTCOME MEASURES beta-Blocker and calcium channel blocker use in the first 90 days after discharge and mortality rates and cardiac hospital readmissions over the 2-year period after discharge , controlling for sociodemographic and baseline risk variables . RESULTS Only 21 % of eligible patients received beta-blocker therapy ; this rate remained unchanged from 1987 to 1991 . Patients were almost 3 times more likely to receive a new prescription for a calcium channel blocker than for a new beta-blocker after their AMIs . Advanced age and calcium channel blocker use predicted underuse of beta-blockers . Controlling for other predictors of survival , the mortality rate among beta-blocker recipients was 43 % less than that for nonrecipients ( RR=0.57 ; 95 % confidence interval [ CI ] , 0.47 - 0.69 ) . Effects on mortality were substantial in all age strata ( 65 - 74 years , 75 - 84 years , and > or = 85 years ) and consistent with the results for elderly subgroups of 2 large RCTs . beta-Blocker recipients were rehospitalized 22 % less often than nonrecipients ( RR=0.78 ; 95 % CI , 0.67 - 0.90 ) . Use of a calcium channel blocker instead of a beta-blocker was associated with a doubled risk of death ( RR= 1.98 ; 95 % CI , 1.44 - 2.72 ) , not because calcium channel blockers had a demonstrable adverse effect , but because they were substitutes for beta-blockers . CONCLUSIONS beta-Blockers are underused in elderly AMI survivors , leading to measurable adverse outcomes . These data suggest that the survival benefits of beta-blockade after an AMI may extend to eligible patients older than 75 years , a group that has been excluded from RCTs BACKGROUND Beta-blocker therapy after acute myocardial infa rct ion ( MI ) improves survival .  Beta-blocker doses used in clinical practice are often substantially lower than those used in the r and omized trials establishing their efficacy . OBJECTIVES This study evaluated the association of beta-blocker dose with survival after acute MI , hypothesizing that higher dose beta-blocker therapy will be associated with increased survival . METHODS A multicenter registry enrolled 7,057 consecutive patients with acute MI . Discharge beta-blocker dose was indexed to the target beta-blocker doses used in r and omized clinical trials , grouped as > 0 % to 12.5 % , > 12.5 % to 25 % , > 25 % to 50 % , and > 50 % of target dose . Follow-up vital status was assessed , with the primary endpoint of time-to-death right-censored at 2 years . Multivariable and propensity score analyses were used to account for group differences . RESULTS Of 6,682 patients with follow-up ( median 2.1 years ) , 91.5 % were discharged on a beta-blocker ( mean dose 38.1 % of the target dose ) . Lower mortality was observed with all beta-blocker doses ( p < 0.0002 ) versus no beta-blocker therapy . After multivariable adjustment , hazard ratios for 2-year mortality compared with the > 50 % dose were 0.862 ( 95 % confidence interval [ CI ] : 0.677 to 1.098 ) , 0.799 ( 95 % CI : 0.635 to 1.005 ) , and 0.963 ( 95 % CI : 0.765 to 1.213 ) for the > 0 % to 12.5 % , > 12.5 % to 25 % , and > 25 % to 50 % of target dose groups , respectively . Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome . CONCLUSIONS These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous r and omized clinical trials compared with lower doses . These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy . ( The PACE-MI Registry Study - Outcomes of Beta-blocker Therapy After Myocardial Infa rct ion [ OBTAIN ] : NCT00430612 ) Given the high prevalence of cardiovascular disease in people with chronic kidney disease ( CKD ) and the clear benefits of mortality reduction observed for most β−blockers in clinical trials , they are relatively underused in CKD patients [ 1,2 ] . The rationale for use of β-blockers in patients with CKD is review ed in detail elsewhere [ 2,3 ] but is summarized in this editorial . Alterations in β- and α-receptor responsiveness are associated with sympathetic over-activity in CKD . This increased sympathetic activity is involved in the genesis of hypertension , and contributes to cardiac complications seen in CKD [ 2,3 ] . The contribution of the sympathetic nervous system to nephropathy progression is documented in sub-totally nephrectomized rats where non-hypotensive doses of β-blockers ameliorate development of glomerulosclerosis and cardiac injury [ 4 ] . In men ,  sympathetic over-activity  , as assessed by sural nerve microneurography , was present in patients on haemodialysis [ 5 ] , stage 4 nephropathy [ 6 ] and in early stage 2 nephropathy among patients with polycystic kidney disease [ 7 ] . The role of the damaged kidney in causing sympathetic over-activity is illustrated by normalization of sympathetic over-activity in haemodialysis patients following bilateral nephrectomy [ 5 ] and in renal allograft recipients when their shrunken native kidneys are removed [ 8 ] . The most common cause of death in stage 3 and higher CKD results from complications of cardiovascular disease . This may be due , in part , to inadequate treatment of blood pressure , where blood pressure goals were not attained and agents known to reduce mortality secondary to cardiovascular causes , i.e. aspirin , ACE inhibitors and β-blockers were not used [ 9 ] . In a separate study , β-blockers were used in fewer than 30 % of haemodialysis patients [ 10 ] . This is surprising , since β-blockers are well-established , evidence -based therapy for reducing cardiovascular risk in hypertension associated with diabetes and after myocardial infa rct ion [ 11,12 ] . Observational studies support definite survival benefits derived from β-blocker use in patients with advanced CKD [ 13,14 ] . Furthermore , a prospect i ve The Swedish trial in old patients with hypertension ( STOP-Hypertension ) is a multicentre , r and omized , double-blind study of beta-blockers/diuretics versus placebo in old hypertensives . Primary end-points are stroke and myocardial infa rct ion ( fatal and non-fatal ) as well as other cardiovascular mortality . To evaluate the logistics of STOP-Hypertension , a pilot study was carried out . All patients aged 70 - 84 years in 31 centres were consecutively registered in a log-book . Altogether 4668 patients were screened : 41.5 % had previously been treated for hypertension and 13.5 % had blood pressures greater than or equal to 180/105 mmHg . Thus , 55 % were ' hypertensive ' . In all , 465 patients ( 18 % of the ' hypertensive ' patients ) started a 3-month washout period ( previously treated , n = 396 ) or a 4-week run-in period ( previously untreated , n = 69 ) period . The most frequent reasons for not starting the run-in/washout were other indications for treatment with beta-blockers/diuretics ( 13 % ) , unwillingness to participate ( 8 % ) or isolated systolic hypertension ( 4 % ) . The pilot study was evaluated after 1 year : 89 patients ( 1.9 % ) had been r and omized , 66 patients ( 1.4 % ) were still in the run-in/washout period and the majority of the remaining patients were not r and omized because they had not reached the inclusion blood pressure ( greater than or equal to 180 mmHg systolic and /or greater than or equal to 105 mmHg diastolic ) following withdrawal of their antihypertensive medication . During the run-in/washout period there were few serious clinical events : one case of myocardial infa rct ion , three patients had strokes ( two fatal ) , 10 developed congestive heart failure , three tachyarrhythmia and two pneumonia ( one fatal ) . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension BACKGROUND The beneficial effects of beta-blockers on long-term outcome after acute myocardial infa rct ion were shown before the introduction of thrombolysis and angiotensin-converting-enzyme ( ACE ) inhibitors . Generally , the patients recruited to these trials were at low risk : few had heart failure , and none had measurements of left-ventricular function taken . We investigated the long-term efficacy of carvedilol on morbidity and mortality in patients with left-ventricular dysfunction after acute myocardial infa rct ion treated according to current evidence -based practice . METHODS In a multicentre , r and omised , placebo-controlled trial , 1959 patients with a proven acute myocardial infa rct ion and a left-ventricular ejection fraction of < /=40 % were r and omly assigned 6.25 mg carvedilol ( n=975 ) or placebo ( n=984 ) . Study medication was progressively increased to a maximum of 25 mg twice daily during the next 4 - 6 weeks , and patients were followed up until the requisite number of primary endpoints had occurred . The primary endpoint was all-cause mortality or hospital admission for cardiovascular problems . Analysis was by intention to treat . FINDINGS Although there was no difference between the carvedilol and placebo groups in the number of patients with the primary endpoint ( 340 [ 35 % ] vs 367 [ 37 % ] , hazard ratio 0.92 [ 95 % CI 0.80 - 1.07 ] ) , all-cause mortality alone was lower in the carvedilol group than in the placebo group ( 116 [ 12 % ] vs 151 [ 15 % ] , 0.77 [ 0.60 - 0.98 ] , p=0.03 ) . Cardiovascular mortality , non-fatal myocardial infa rct ions , and all-cause mortality or non-fatal myocardial infa rct ion were also lower on carvedilol than on placebo . INTERPRETATION In patients treated long-term after an acute myocardial infa rct ion complicated by left-ventricular systolic dysfunction , carvedilol reduced the frequency of all-cause and cardiovascular mortality , and recurrent , non-fatal myocardial infa rct ions . These beneficial effects are additional to those of evidence -based treatments for acute myocardial infa rct ion including ACE inhibitors BACKGROUND Previous prospect i ve outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure . AIM The primary objective is to determine whether rosuvastatin ( 10 mg ) reduces the combined endpoint of cardiovascular mortality , non-fatal myocardial infa rct ion or non-fatal stroke ( time to first event ) . The first secondary endpoint is all-cause mortality . METHODS CORONA is a r and omized , double-blind , placebo-controlled trial . Briefly , men and women , aged > or = 60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or = 0.40 ( NYHA class III and IV ) or < or = 0.35 ( NYHA class II ) were eligible if they were not using or in need of cholesterol lowering drugs .  RESULTS Mean age was 73 years ( n=5016 ; 24 % women ) , with 37 % in NYHA II and 62 % in NYHA III , ejection fraction 0.31 , total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infa rct ion , 63 % hypertension , and 30 % diabetes . Patients are well treated for heart failure with 90 % on loop or thiazide diuretics , 42 % aldosterone antagonists , 91 % ACE inhibitor or AT-I blocker , 75 % beta-blockers , and 32 % digitalis . CONCLUSION CORONA is important for three main reasons : ( 1 ) A positive result is very important because of the high risk of the population studied , the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society , and the health economic issues involved . ( 2 ) If negative , new mechanistic questions about heart failure have to be raised . ( 3 ) If neutral we can avoid unnecessary polypharmacy Myocardial infa rct ion , sudden cardiac death , cerebrovascular accidents , blood pressure control and treatment tolerability were studied in a r and omized double-blind trial conducted in 6357 men and women aged 40 - 64 years with uncomplicated essential hypertension ( diastolic blood pressures 100 - 125 mmHg ) . At the start of the trial 3185 patients received treatment based on a beta-blocker ( oxprenolol )  , while in the remaining 3172 placebo replaced oxprenolol .  Supplementary drugs , excluding beta-blockers , were used as necessary in both treatment groups , with the aim of reducing diastolic pressure to 95 mmHg or less . Patients were followed for 3 - 5 years , a total of 25 651 patient years at risk . In most respects the two groups fared equally well ; sudden death ( relative risk [ RR ] 1.08 ; 95 % confidence interval [ Cl ] 0.68 and 1.72 ) , myocardial infa rct ion ( RR 0.83 ; Cl 0.59 and 1.16 ) and cerebrovascular accident ( RR 0.97 ; Cl 0.64 and 1.47 ) rates were similar . Beta-blocker based therapy was associated with significantly lower average blood pressures , earlier ECG normalization , less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension . Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability . In smokers the cardiac event rate was doubled . We propose that beta-blocker treatment effects depend on smoking status , with a significant interaction benefiting non-smoking men . Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events . Proportional hazards analysis also underlines the importance of other cardiovascular risk factors . The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients BACKGROUND Although r and omized clinical trials have demonstrated that beta-blocker therapy is effective in reducing mortality after acute myocardial infa rct ion ( AMI ) , many of these studies excluded patients who undergo coronary revascularization . However , the clinical practice guidelines established by the American College of Cardiology and the American Heart Association recommend that beta-blocker therapy be considered for patients who underwent successful revascularization after AMI . METHODS Using data from the Cooperative Cardiovascular Project , we compared the initiation of beta-blocker therapy at discharge in patients aged 65 years or older who underwent coronary artery bypass surgery ( CABG ) or percutaneous transluminal coronary angioplasty ( PTCA ) during their hospitalization for AMI with that of patients who did not undergo revascularization . We then examined whether beta-blocker therapy was associated with lower 1-year mortality between revascularized and nonrevascularized groups . RESULTS After excluding patients with contraindications to beta-blocker therapy , 84 457 patients remained in the study sample . Of these , 8482 patients underwent CABG , and 13 997 patients underwent PTCA . After adjusting for demographic and clinical factors , we found that these patients were less likely to initiate beta-blocker therapy after CABG ( odds ratio [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.41 - 0.47 ) or PTCA ( OR , 0.89 ; 95 % CI , 0.85 - 0.93 ) relative to the nonrevascularized group . After adjusting for potential confounders , beta-blockers were significantly associated with lower 1-year mortality in patients who underwent CABG ( hazard ratio [ HR ] , 0.70 ; 95 % CI , 0.55 - 0.89 ) or PTCA ( HR , 0.86 ; 95 % CI , 0.74 - 1.00 ) , similar to that of the non-revascularized group ( HR , 0.83 ; 95 % CI , 0.80 - 0.87 ) . CONCLUSIONS Therapy after AMI with beta-blockers appears to be as effective in reducing 1-year mortality for elderly patients who have undergone CABG or PTCA as for a nonrevascularized group . Our findings suggest that routine use of beta-blockers should be considered for patients who undergo revascularization after AMI PURPOSE To determine the rates of patient adherence to key evidence -based therapies at 6 months after hospital discharge for an acute coronary syndrome . METHODS In this nonr and omized , prospect i ve , multinational , multicenter study , adherence to aspirin , beta-blockers , statins , or angiotensin-converting enzyme ( ACE ) inhibitors 6 months after discharge for myocardial infa rct ion or unstable angina was assessed in 21,408 patients aged 18 years or older . Patients were enrolled at 104 tertiary and community hospitals representing a broad range of care facilities and practice setting s ( e.g. , teaching vs. nonteaching ) . RESULTS Of 13,830 patients , discontinuation of therapy was observed at 6-month follow-up in 8 % of those taking aspirin on discharge , 12 % of those taking beta-blockers , 20 % of those taking ACE inhibitors , and 13 % of those taking statins . In a multivariate analysis , adherence to beta-blocker therapy  was higher in patients with a myocardial infa rct ion ( odds ratio [ OR ] = 1.25 ; 95 % confidence interval [ CI ] : 1.06 to 1.47 ) , hypertension ( OR = 1.33 ; 95 % CI : 1.15 to 1.54 ) , ST-segment elevation myocardial infa rct ion ( OR = 1.33 ; 95 % CI : 1.11 to 1.61 ) , or non-ST-segment elevation myocardial infa rct ion ( OR = 1.25 ; 95 % CI : 1.08 to 1.45 ) .  Aspirin adherence was higher among patients cared for by cardiologists ( OR = 1.45 ; 95 % CI : 1.19 to 1.75 ; P < 0.001 ) than among those cared for by nonspecialists . Male sex and prior heart failure were associated with improved adherence to ACE inhibitor therapy . Hypertension was associated with poorer adherence to statin therapy ( OR = 0.85 ; 95 % CI : 0.74 to 0.99 ; P = 0.04 ) . CONCLUSION Among patients prescribed key evidence -based medications at discharge , 8 % to 20 % were no longer taking their medication after 6 months . The reasons for noncompliance are complex , and may be eluci date d by future studies of medical and social determinants BACKGROUND beta-Blockers have been shown to be beneficial in the treatment and prevention of  heart failure ( HF )  in the general population , but they have not been assessed for their association with nonfatal HF in a nationally representative population of long-term dialysis patients . METHODS We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data System ( USRDS ) Wave 2 who were Medicare eligible at the start of the study . Analysis was stratified by the presence or absence of a known diagnosis of HF , and patients followed up until December 31 , 2000 . Cox regression analysis , including propensity scores , was used to model adjusted hazard ratios for beta-blocker use ( assessed separately by cardioselective activity and lipid solubility ) with time to the first Medicare institutional cl aim for HF , cardiovascular-related death , or death from any cause . RESULTS In patients without a previous history of HF , beta-blocker use was significantly associated with a lower adjusted risk of HF ( adjusted hazard ratio , 0.69 ; 95 % confidence interval , 0.52 - 0.91 ; P=.008 ) , with a similar reduction in risk of cardiac-related and all-cause death . beta-Blocker use had no statistically significant associations with outcomes in patients with previous HF . CONCLUSIONS In dialysis patients without a previous documented history of HF , beta-blocker use was associated with a lower risk of new HF , cardiovascular death , and death from any cause . No such associations were seen for dialysis patients with a previous history of HF . These results are hypothesis generating only and should be confirmed in r and omized trials OBJECTIVES We sought to determine the use and association with one-year mortality of beta-blocker therapy for the treatment of acute myocardial infa rct ion ( AMI ) in elderly diabetic patients and to examine whether beta-blocker therapy was associated with increased rates of hospital readmission for diabetic complications traditionally associated with beta-blockers . BACKGROUND Although many r and omized trials have demonstrated that beta-blockers are effective in reducing mortality after AMI , some experts are concerned about the use of beta-blockers in diabetic patients . Little is known about the effectiveness and complication rate of beta-blocker therapy after AMI for elderly diabetics in community practice setting s. METHODS We conducted a retrospective cohort study using the National Cooperative Cardiovascular Project , which contained data abstract ed from hospital medical records of Medicare beneficiaries admitted with an AMI during 1994 and 1995 . RESULTS Out of 45,308 patients without contraindications to beta-blocker therapy , 7.4 % were insulin-treated diabetics and 18.5 % were non-insulin-treated diabetics .  Beta-blockers were prescribed at discharge for 45 % of insulin-treated diabetics , 48.1 % of non-insulin-treated diabetics and 51 % of nondiabetics ( p < 0.001 ) . After adjusting for demographic and clinical factors , diabetics continued to be less likely to receive beta-blockers at discharge compared with nondiabetics ( odds ratio [ OR ] for insulin-treated diabetics 0.88 , 95 % confidence interval [ CI ] 0.82 to 0.96 ; OR for non-insulin-treated diabetics 0.93 , 95 % CI 0.88 to 0.98 ) . After adjusting for potential confounders , beta-blockers were associated with lower one-year mortality for insulin-treated diabetics ( hazard ratio [ HR ] = 0.87 , 95 % CI 0.72 to 1.07 ) , non-insulin-treated diabetics ( HR = 0.77 , 95 % CI 0.67 to 0.88 ) and nondiabetics ( HR = 0.87 , 95 % CI 0.80 to 0.94 ) . Beta-blocker therapy was not significantly associated with increased six-month readmission rates for diabetic complications among diabetics and nondiabetics . CONCLUSIONS Beta-blockers are associated with a lower one-year mortality rate for elderly diabetic patients to a similar extent as for nondiabetics , without increased risk of readmission for diabetic complications . Increasing the use of beta-blockers in elderly diabetic patients represents an opportunity to improve the care and outcomes of these patients after AMI The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized The influence of digitalis therapy on survivors of acute myocardial infa rct ion was examined in the  placebo-treated patients from the Beta-Blocker Heart Attack Trial ( BHAT ) . Two hundred fifty ( 13 % ) of the 1,921 placebo-treated patients were receiving digitalis at the time of r and omization . Patients receiving digitalis  differed from those not receiving digitalis in such baseline characteristics as age , prior history of heart failure , prior myocardial infa rct ion and angina pectoris . They also experienced a higher proportion of in-hospital complications including pulmonary edema , persistent hypotension , atrial fibrillation and heart failure in addition to a greater prevalence of complex ventricular premature beats . The total mortality rate over a mean 25 month follow-up period for digitalis-treated patients was 20.4 % compared with 8.2 % for patients not receiving digitalis ; the odds ratio was 2.87 ( p less than 0.05 ) . When the mortality rates were adjusted for heart failure and ventricular premature beat complexity , patients receiving digitalis again demonstrated a higher mortality rate , although the adjusted odds ratio was now lower ( 1.70 ) . When the patients receiving or not receiving digitalis were compared by a multiple logistic regression analysis adjusting for 17 independent variables predictive of mortality , the use of digitalis was no longer independently predictive of total mortality ( adjusted odds ratio 1.07 ) . These data indicate that patients receiving digitalis  had more extensive cardiovascular disease and greater morbidity than patients not  receiving digitalis . Their subsequent higher mortality rate was probably related to these factors rather than to digitalis therapy Objective : A case control study has reported a 60 % higher risk of myocardial infa rct ion in hypertensives treated with a calcium channel blocker ( CCB ) . We examined the Department of Health Hypertension Care Computing Project ( DHCCP ) data to see if we could confirm or refute this suggestion . Design : Two case control studies , matched and unmatched , plus two longitudinal studies from 1 year of presentation , one for all subjects given a CCB  for more than 1 year compared with those not given this drug , and the second comparing survival on the different drugs initially given between 3 and 12 months of follow-up . Subjects : A total of 9328 subjects were included in the analyses and 2154 died . Of these , 6406 received one or more of the following index drugs : 26 % a calcium channel blocker ( CCB ) ; 84 % a diuretic ; 29 % alpha methyldopa ; 12 % a beta-blocker ( BB ) ; and 11 % an angiotensin-converting enzyme ( ACE ) inhibitor . The CCBs were nifedipine , diltiazem or verapamil . Results : In the case control studies a group given diuretics ± other treatments ( but not including one of the index drugs ) provided a reference group with a relative risk ( RR ) of 1.0 . In the matched case control study the adjusted RR for a CCB  without a diuretic was 1.32 ( 95 % CI 0.64–2.70 ) for IHD mortality and 1.05 ( 95 % CI 0.60–1.84 ) for cardiovascular mortality . Similar results were observed for methyldopa , BBs and ACE inhibitors . The results in the unmatched case control analysis were also similar . The longitudinal study comparing all those treated for over 1 year with a CCB with all other treatments showed a RR for total mortality of 1.03 ( 95 % CI 0.85–1.25 ) . The longitudinal study of total mortality according to treatment initiated at 3–12 months found results of a similar magnitude for CCBs , methyldopa and BBs . Conclusions : The reference diuretic group had less severe cardiovascular disease than other groups . Treatment with a CCB , BB or methyldopa was associated with an excess mortality in comparison with this reference group . The excess was similar in the different drug groups CONTEXT Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk , but the benefit compared with other drug classes is controversial . OBJECTIVE To determine whether initial therapy with controlled-onset extended-release ( COER ) verapamil is equivalent to a physician 's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized clinical trial conducted at 661 centers in 15 countries . A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31 , 2000 . After a mean of 3 years of follow-up , the sponsor closed the study before unblinding the results . INTERVENTION Initially , 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide . Other drugs ( eg , diuretic , beta-blocker , or an angiotensin-converting enzyme inhibitor ) could be added in specified sequence if needed . MAIN OUTCOME MEASURES First occurrence of stroke , myocardial infa rct ion , or cardiovascular disease-related death . RESULTS Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group . There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group ( hazard ratio [ HR ] , 1.02 ; 95 % confidence interval [ CI ] , 0.88 - 1.18 ; P = .77 ) . For fatal or nonfatal stroke , the HR was 1.15 ( 95 % CI , 0.90 - 1.48 ) ; for fatal or nonfatal myocardial infa rct ion , 0.82 ( 95 % CI , 0.65 - 1.03 ) ; and for cardiovascular disease-related death , 1.09 ( 95 % CI , 0.87 - 1.37 ) . The HR was 1.05 ( 95 % CI , 0.95 - 1.16 ) for any prespecified cardiovascular disease-related event and 1.08 ( 95 % CI , 0.93 - 1.26 ) for all-cause mortality . Nonstroke hemorrhage was more common with participants in the COER-verapamil group ( n = 118 ) compared with the atenolol or hydrochlorothiazide group ( n = 79 ) ( HR , 1.54 [ 95 % CI , 1.16 - 2.04 ] ; P = .003 ) . More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil ( 99/277 ) and atenolol or hydrochlorothiazide ( 88/274 ) groups ; HR , 1.15 ( 95 % CI , 0.86 - 1.53 ) . CONCLUSIONS The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker . When considered in the context of other trials of calcium antagonists , these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment BACKGROUND Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery . Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality . They may , therefore , benefit from perioperative beta-blockade . METHODS The Diabetic Postoperative Mortality and Morbidity ( DIPOM ) trial is an investigator-initiated and -controlled , central ly r and omized , double-blind , placebo-controlled , multicenter trial . We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive , > or=40 years old , and undergoing noncardiac surgery . The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery . The primary outcome measure is the composite of all-cause mortality , acute myocardial infa rct ion , unstable angina , or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization . Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public data bases . The study was powered on the basis of an estimated 30 % 1-year event rate in the placebo arm and a 33 % relative risk reduction in the metoprolol arm . The median follow-up period was 18 months . RESULTS Enrollment started in July 2000 and ended in June 2002 . A total of 921 patients were r and omized , and 54 % of these patients had known cardiac disease , hypertension , or both . CONCLUSION The results of this study may have implication s for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery BACKGROUND Noncardiac surgery is associated with significant cardiovascular mortality , morbidity , and cost . Small trials of beta-blockers suggest that they may prevent cardiovascular events in patients undergoing noncardiac surgery , but trial results are inconclusive . We have initiated the POISE trial to definitively establish the effects of beta-blocker therapy in patients undergoing noncardiac surgery . METHODS The POISE trial is a blinded , r and omized , and controlled trial of controlled-release metoprolol versus placebo in 10000 patients at risk for a perioperative cardiovascular event who are undergoing noncardiac surgery . Patients will receive the study drug 2 to 4 hours before surgery and subsequently for 30 days . The primary outcome is a composite of cardiovascular death , nonfatal myocardial infa rct ion , and nonfatal cardiac arrest at 30 days . Patients will also be followed for events at 1 year . RESULTS To date , the POISE trial has recruited > 6300 patients in 182 centers in 21 countries . Currently , the patients ' mean age is 69 years ; 63 % are males , 43 % have a history of coronary artery disease , 43 % have a history of peripheral arterial disease , and 30 % have diabetes . Most participants have undergone vascular ( 42 % ) , intraabdominal ( 23 % ) , or orthopedic ( 19 % ) surgery . CONCLUSIONS The POISE trial is a large international trial that will provide a reliable assessment of the effects of beta-blocker therapy in patients undergoing noncardiac surgery BACKGROUND There is no direct evidence that beta-blockers improve mortality in burn victims .  Beta-blockers attenuate hypermetabolic states in burned children , and perioperative use in elective adult cases has beneficial effects , which suggests that beta-blockers may also improve burn outcomes . However , beta-blockers decrease cardiac output and may decrease oxygen delivery , and theoretically may increase mortality . What is the effect of beta-blockers on healing time and mortality in burn patients ? METHODS This was a retrospective cohort study . We identified three cohorts of adult burn patients between 1996 and 2001 : all who were on beta-blockers ( BB ) before their injury ( PMH BB ) ; all who were initiated on BB during their hospitalization for management of hypertension or tachyarrhythmia ( HOSP BB ) ; and control , who were never treated with beta-blockers .  For each patient in the PMH BB and HOSP BB groups , two patients were placed in the control cohort by matching age and total body surface area burn . Premorbid conditions such as diabetes , hypertension , cardiac disease , renal insufficiency , and diuretic and calcium channel blocker use were analyzed . Multivariate regression models were used to identify independent modifiers . RESULTS There were 21 PMH BB , 22 HOSP BB , and 86 control patients . All PMH BB patients remained on their BB regimen in the hospital . HOSP BB patients were initiated on beta-blockers at a mean of 8.8 days postinjury . There were no differences in age ( mean , 58 + /- 17 years ) , total body surface area burned ( mean , 14 + /- 12 % ) , or mechanism of injury among the cohorts . The mortality rate was 5 % for the PMH BB cohort , 27 % for the HOSP BB cohort , and 13 % for controls . The mean healing times were 51 + /- 29 days for PMH BB patients , 79 + /- 54 days for HOSP BB patients , and 60 + /- 39 for controls . In multivariate analyses , PMH BB was associated with a significant decrease in fatal outcome and healing time ( p < or = 0.05 compared with control ) . CONCLUSION Beta-blockers have the potential to improve adult burn outcomes . Postinjury treatment should be studied in a r and omized , clinical trial Cardiovascular disease ( CVD ) is a major cause of morbidity and mortality among patients with chronic renal insufficiency ( CRI ) .  beta-Adrenergic blockers , acetylsalicylic acid ( ASA ) , angiotensin-converting enzyme ( ACE ) inhibitors , and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) all reduce CVD mortality , but little is known about the extent to which these medications are used in patients with CRI . This study , a prospect i ve cross-sectional study of consecutive patients seen by nephrologists in four Canadian centers for follow-up of progressive CRI in 1999 , was performed to investigate the prevalence of coronary risk factors and use of cardioprotective medications among patients with CRI . Patients had creatinine clearances of 75 mL/min or less but were not on dialysis therapy . Three hundred four consecutive patients meeting the inclusion criteria were enrolled . Mean age was 60.8 + /- 15.7 years , mean creatinine clearance was 30.3 + /- 18 mL/min , and the case mix of kidney diseases was similar to that in the Canadian Organ Replacement Registry data . One hundred seventeen of 304 patients ( 38.5 % ) had a history of previous CVD , and the prevalence of CVD was greater in patients with more severe CRI . Two hundred forty-three patients ( 79.9 % ) had a history of hypertension , 132 patients ( 43.4 % ) had hyperlipidemia , 114 patients ( 37.5 % ) had diabetes mellitus , and 71 patients ( 27.3 % ) were smokers . Thirty-five percent of the patients with CVD had blood pressures greater than 140/90 mm Hg ; 103 patients ( 33.9 % ) were administered beta-blockers ; 196 patients ( 64.5 % ) , ACE inhibitors or angiotensin-receptor blockers ; 83 patients ( 27.3 % ) , ASA ; and 56 patients ( 18.4 % ) , statins . Patients with diabetes were not more likely than those without diabetes to be prescribed cardioprotective medications . CVD is common in the predialysis population , and its prevalence increases with more severe kidney failure . Despite this , the use of cardioprotective medications  is relatively low , and many patients had suboptimal blood pressure control . Given the high burden of disease in these patients , beta-blockers and ACE inhibitors should be used to control hypertension and /or for cardioprotection , and the increased use of ASA and statins should be considered PURPOSE R and omized trials have shown that beta-blockers prevent morbidity and mortality in heart failure . However , whether beta-blockers are effective in older patients or those with conditions that would have led to their exclusion from these trials remains unclear . SUBJECTS AND METHODS The associations between beta-blocker use and outcomes were examined in a population -based cohort of 11,942 older ( age > /=65 years ) patients with incident heart failure between 1994 and 1999 . Cox proportional hazards models were used to adjust for propensity scores , age , sex , comorbid conditions , and other medications . RESULTS The mean ( + /- SD ) age of the patients was 79 + /- 8 years , 5819 ( 49 % ) were men , and 2569 ( 22 % ) had Charlson comorbidity scores of at least 2 . During follow-up ( median , 21 months ) , 3539 patients were hospitalized for heart failure and 6757 died . Overall , 1162 patients received beta-blockers . After adjustment , beta-blocker use was associated with substantial reductions in all-cause mortality ( hazard ratio [ HR ] = 0.72 ; 95 % confidence interval [ CI ] : 0.65 to 0.80 ) , mortality due to heart failure ( HR = 0.65 ; 95 % CI : 0.47 to 0.90 ) , and hospitalizations for heart failure ( HR = 0.82 ; 95 % CI : 0.74 to 0.92 ) . These endpoints were less frequent in patients treated with beta-blockers than in untreated patients in all examined subgroups . All doses of beta-blockers were associated with benefit , but there was a trend towards greater benefit in patients prescribed higher doses . CONCLUSIONS The benefits of beta-blockers seen in r and omized trials extend to older patients and to those with conditions that would have led to their exclusion from the trials . There is a need for a r and omized trial comparing different doses of beta-blockers in heart failure Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a  diuretic ( n = 3272 ) or a  beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death .  Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent Fifty-five patients with mild to moderate , renal or essential hypertension were admitted to a double blind cross-over trial of 18 weeks , involving treatment periods with placebo , the thiazide bendrofluazide ( 15 mg daily ) and the beta blocker atenolol ( 600 mg daily ) . Compared to the placebo period ( 190/117 mm Hg ) the hypotensive effect of atenolol ( -24/16 mm Hg ) was more pronounced than the hypotensive effect of bendrofluazide ( -17/6 mm Hg ) . Arguments in favor of initiating antihypertensive drug therapy with beta blocker were its more powerful hypotensive effect , the quicker onset of its action , less metabolic disturbance , decreased frequency of complaints and patient 's preference . On thiazides body weight and the frequency of swollen ankles decreased . Plasma renin concentration was not found to have a strong predicting power for the hypotensive effect of atenolol or bendrofluazide but low renin patients showed a more pronounced blood pressure decrease on bendrofluazide and high renin patients , especially essential hypertensives , on atenolol . While these points can be a guide to therapy today , the preference of one drug over the other must eventually be based on their relative efficacy in decreasing morbidity and mortality from the hypertensive disease OBJECTIVES Congestive heart failure ( CHF ) is characterized by an initial compensatory , but subsequently deleterious , activation of both the renin-angiotensin ( RAS ) and the sympathetic nervous system ( SNS ) . Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF . Carvedilol , a mixed alpha and beta-blocker with antioxidant properties , and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF . However , beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma . The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings . The aims of the present study were to examine and compare the cardiovascular , autonomic , and clinical effects of additional alpha-1 , or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF . METHODS Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics , were r and omized to 3 groups of similar demographics according to a single blind , parallel group design . The patients were aged 53 + /- 6 years , and comprised 14 men and 14 women , with a mean cardiothoracic ratio of 0.66 + /- 0.03 , and ejection fraction of 0.38 + /- 0.10 , 60 % hypertensive etiology . Group 1 patients received 5 mg enalapril alone , group 2 received 5 mg enalapril + 1 mg prazosin , and group 3 received 5 mg enalapril + 50 mg atenolol . All medication was taken daily for 4 weeks . Blood pressure , heart rate , pressure rate product , 6-minute walk test , NYHA class , and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment . Two-way repeated measures ANOVA , and a one-way ANOVA were used in data analysis . RESULTS The 3 treatments caused significant ( P<.001 ANOVA ) and similar improvements for the NYHA class ( -1.0 to -1.6 ) , and increased the 6-minute distance covered ( + 130 m to + 205 m ) . Although no treatment differences were observed , a trend suggesting a greater improvement with  enalapril + atenolol  became apparent . By the fourth week , the sympathoplegic treatments , enalapril + atenolol , and enalapril + prazosin , caused significant reductions in the pressure rate product ( -3726 + /- 1885 mm Hg x beats/min ; -3498 + /- 396 mm Hg beats/min , respectively ) , ( compared to enalapril alone ( -1349 + /- 894 mm Hg x beats/min ) ( P<.001 ANOVA ) . During the Valsalva maneuver , the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol ( 944 + /- 66 msec ) or with enalapril + prazosin ( 825 + /- 48 msec ) , compared to enalapril alone ( 760 + /- 45 msec ) ( P<.001 ANOVA ) . The phase II Valsalva tachycardia were similar between treatments . The respiratory sinus arrhythmia ratio increased significantly ( P<.005 ANOVA ) and equally on all treatments . However , the pressor and chronotropic responses to forearm isometric h and grip increased significantly on the enalapril + prazosin combination ( P<.02 ) , compared to the other treatments . CONCLUSIONS Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF , but also the result ant improvement in exercise tolerance and NYHA class . Compared to using ACE inhibition alone , the combined therapies caused a marked reduction in the pressure rate product , an index of myocardial oxygen consumption , and a greater enhancement of cardiac parasympathetic activity . Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade . Conversely , the pressor and chronotropic abnormalities during forearm isometric h and grip in CHF , were normalized by alpha-1 , but not beta-1 , blockade . Thus , the combined reflex cardiac vagal augmentation following selective beta-1 blockade , and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition , may be of major therapeutic and prognostic benefit in Blacks with non-ischemic ( hypertensive ) CHF stabilized on digoxin and diuretics OBJECTIVE To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors  have a different risk of mortality than those using beta-blockers . DESIGN A prospect i ve cohort study continuing from 1988 through 1992 . SETTING Three communities of the Established Population s for Epidemiologic Studies of the Elderly . PARTICIPANTS Hypertensive participants aged > or = 71 years ( n = 906 ) who had no evidence of congestive heart failure and who were using either beta-blockers ( n = 515 ) , verapamil ( n = 77 ) , diltiazem ( n = 92 ) , nifedipine ( n = 74 ) , or ACE inhibitors ( n = 148 ) .  Nifedipine was of the short acting variety . MEASUREMENTS The main outcome measure was all-cause mortality . Age , gender , smoking , HDL-cholesterol , blood pressure , intake of digoxin and diuretics , physical disability , self-perceived health , and comorbid conditions were examined as confounders . RESULTS During 3538 person-years of follow-up , 188 participants died ( 53 deaths per 1000 person-years ) . Compared with beta-blockers , after adjusting for age , gender , comorbid conditions and other health-related factors , the relative risks ( 95 % confidence interval ) for mortality associated with use of verapamil , diltiazem , nifedipine , and ACE inhibitors were 0.8 ( 0.4 - 1.4 ) , 1.3 ( 0.8 - 2.1 ) , 1.7 ( 1.1 - 2.7 ) , and 0.9 ( 0.6 - 1.4 ) , respectively . The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics . Higher doses of nifedipine were associated with higher mortality . CONCLUSION Compared with beta-blockers , use of short acting nifedipine was associated with decreased survival in older hypertensive persons . However , selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted , and final conclusions will depend on clinical trials Abstract Beta-blocking drugs may be more effective than saluretic diuretics in reducing the total mortality and incidence of myocardial infa rct ion , sudden death and stroke in middle-aged men with mild to moderate hypertension . To test this hypothesis , an international multicenter , r and omized study is in progress , and its design and some early results are presented here . It is probable that 4,000–5,000 men will need to be enrolled for five years to show a statistically significant difference between treatments . Identical control of blood pressure in the two treatment groups is m and atory , and has been achieved using a fixed therapeutic schedule . The ongoing study will be completed during 1985–1990 Summary The International Prospect i ve Primary Prevention Study in Hypertension ( IPPPSH ) , an international multicentre r and omised double-blind trial , compares antihypertensive regimens containing a beta-blocker ( oxprenolol ) with regimens not containing a beta-blocker . The protocol was developed and the study started in 1977 . 6,357 patients fulfilled the inclusion criteria and were enrolled by the end of 1980 . Patients have been treated in 6 countries for 3 to 5 years by 288 general practitioner and hospital out-patient centres . Follow-up was finished at the end of 1983 when 25,651 years of patient treatment had been completed . At entry patients had a diastolic pressure of 100–125 mmHg with no clinical evidence of cerebrovascular or ischaemic heart disease ( W.H.O. Stages I and II hypertension ) . The study was design ed to examine three main objectives : any influence of oxprenolol on the incidence of myocardial infa rct ion and sudden death compared with antihypertensive therapy not containing a beta-blocker ; the influence of cerebrovascular accidents in the same two groups ; a comparison of the antihypertensive effectiveness , and the subjective and objective tolerability of the regimens . This paper summarises the objectives and methodology , and examines r and omisation between the two treatment groups at entry into the IPPPSH CONTEXT Hypertension is associated with a significantly increased risk of morbidity and mortality . Only diuretics and beta-blockers have been shown to reduce this risk in long-term clinical trials . Whether newer antihypertensive agents reduce the incidence of cardiovascular disease ( CVD ) is unknown . OBJECTIVE To compare the effect of doxazosin , an alpha-blocker , with chlorthalidone , a diuretic , on incidence of CVD in patients with hypertension as part of a study of 4 types of antihypertensive drugs : chlorthalidone , doxazosin , amlodipine , and lisinopril . DESIGN R and omized , double-blind , active-controlled clinical trial , the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial , initiated in February 1994 . In January 2000 , after an interim analysis , an independent data review committee recommended discontinuing the doxazosin treatment arm based on comparisons with chlorthalidone . Therefore , outcomes data presented herein reflect follow-up through December 1999 . SETTING A total of 625 centers in the United States and Canada . PARTICIPANTS A total of 24,335 patients ( aged > or = 55 years ) with hypertension and at least 1 other coronary heart disease ( CHD ) risk factor who received either doxazosin or chlorthalidone .  INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n=15,268 ) , or doxazosin , 2 to 8 mg/d ( n=9067 ) , for a planned follow-up of 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome measure was fatal CHD or nonfatal myocardial infa rct ion ( MI ) , analyzed by intent to treat ; secondary outcome measures included all-cause mortality , stroke , and combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , congestive heart failure [ CHF ] , and peripheral arterial disease ) ; compared by the chlorthalidone group vs the doxazosin group . RESULTS Median follow-up was 3.3 years . A total of 365 patients in the doxazosin group and 608 in the chlorthalidone group had fatal CHD or nonfatal MI , with no difference in risk between the groups ( relative risk [ RR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.90 - 1.17 ; P=.71 ) . Total mortality did not differ between the doxazosin and chlorthalidone arms ( 4-year rates , 9.62 % and 9.08 % , respectively ; RR , 1.03 ; 95 % CI , 0.90 - 1.15 ; P=.56 . ) The doxazosin arm , compared with the chlorthalidone arm , had a higher risk of stroke ( RR , 1.19 ; 95 % CI , 1.01 - 1.40 ; P=.04 ) and combined CVD ( 4-year rates , 25.45 % vs 21.76 % ; RR , 1.25 ; 95 % CI , 1.17 - 1.33 ; P<.001 ) . Considered separately , CHF risk was doubled ( 4-year rates , 8.13 % vs 4.45 % ; RR , 2.04 ; 95 % CI , 1.79 - 2.32 ; P<.001 ) ; RRs for angina , coronary revascularization , and peripheral arterial disease were 1.16 ( P<.001 ) , 1.15 ( P=.05 ) , and 1.07 ( P=.50 ) , respectively . CONCLUSION Our data indicate that compared with doxazosin , chlorthalidone yields essentially equal risk of CHD death/nonfatal MI but significantly reduces the risk of combined CVD events , particularly CHF , in high-risk hypertensive patients Background The benefits of treating hypertension in elderly diabetic patients , in terms of achieving reductions in cardiovascular morbidity and mortality , have been documented in several recent prospect i ve trials . There has , however , been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infa rct ion in this group of patients . Design STOP Hypertension-2 was a prospect i ve , r and omized , open trial with blinded endpoint evaluation . Methods We studied 6614 elderly patients aged 70–84 years ; 719 of them had diabetes mellitus at the start of the study ( mean age 75.8 years ) . Patients were r and omly assigned to one of three treatment strategies : conventional antihypertensive drugs ( diuretics or β-blockers ) , calcium antagonists , or angiotensin converting enzyme ( ACE ) inhibitors . Results Reduction in blood pressure was similar in the three treatment groups of diabetics . The prevention of cardiovascular mortality was also similar ; the frequency of this primary endpoint did not differ significantly between the three groups . There were , however , significantly fewer ( P = 0.025 ) myocardial infa rct ions during ACE inhibitor treatment ( n = 17 ) than during calcium antagonist treatment ( n = 32 ; relative risk 0.51 , 95 % confidence interval 0.28–0.92 ) ; but a ( non-significant ) tendency to more strokes during ACE inhibitor treatment ( n = 34 compared with n = 29 ; relative risk 1.16 , 95 % confidence interval 0.71–1.91 ) . Conclusion Treatment of hypertensive diabetic patients with conventional antihypertensive drugs ( diuretics , β-blockers , or both ) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors OBJECTIVES This was a retrospective analysis to determine the effect of diabetes on outcome in patients with advanced heart failure ( HF ) , and to determine the effect of beta-blockade in patients with HF with and without diabetes mellitus . BACKGROUND In chronic HF the impact on clinical outcomes and therapeutic response of the prevalent comorbid condition diabetes mellitus has not been extensively investigated . METHODS We assessed the impact of diabetes on prognosis and effectiveness of beta-blocker therapy with bucindolol in patients with HF enrolled in the Beta-Blocker Evaluation of Survival Trial ( BEST ) . We conducted a retrospective analysis to examine the prognosis of patients with advanced HF with and without diabetes , and the effect of beta-blocker therapy on mortality and HF progression or myocardial infa rct ion ( MI ) . The data base was the 2,708 patients with advanced HF ( 36 % with diabetes and 64 % without diabetes ) who were r and omized to the beta-blocker bucindolol or placebo in BEST and followed for mortality , hospitalization , and MI for an average of two years . RESULTS Patients with diabetes had more severe chronic HF  and more coronary risk factors than patients without diabetes . Diabetes was independently associated with increased mortality in patients with ischemic cardiomyopathy ( adjusted hazard ratio 1.33 , 95 % confidence interval 1.12 to 1.58 , p = 0.001 ) , but not in those with a nonischemic etiology ( adjusted hazard ratio 0.98 , 95 % confidence interval 0.74 to 1.30 , p = 0.89 ) . Compared with patients without diabetes , in diabetic patients beta-blocker therapy was at least as effective in reducing death or HF hospitalizations , total hospitalizations , HF hospitalizations , and MI . Ventricular function and physiologic responses to beta-blockade were similar in patients with and without diabetes . CONCLUSIONS Diabetes worsens prognosis in patients with advanced HF , but this worsening appears to be limited to patients with ischemic cardiomyopathy . In advanced HF beta-blockade is effective in reducing major clinical end points in patients with and without diabetes BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure Diuretics and & bgr;-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials . No study has compared newer more costly antihypertensive agents ( calcium antagonists , ACE inhibitors , and & agr;-adrenergic blockers ) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients . The study is a r and omized , double-blind , active-controlled clinical trial design ed to determine whether the incidence of the primary outcome , fatal coronary heart disease or nonfatal myocardial infa rct ion , differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs . Men and women aged ≥55 years with at least 1 other cardiovascular disease risk factor were r and omly assigned to chlorthalidone ( 12.5 to 25 mg/d ) , amlodipine ( 2.5 to 10 mg/d ) , lisinopril ( 10 to 40 mg/d ) , or doxazosin ( 2 to 8 mg/d ) for planned follow-up of 4 to 8 years . This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) participants . A total of 42 448 participants were r and omized from 625 sites in the United States , Canada , Puerto Rico , and the US Virgin Isl and s. The mean age was 67 years , with 35 % aged ≥70 years . Among those r and omized , 36 % were black , 19 % were Hispanic , and 47 % were women . The sample includes a high proportion of people with diabetes ( 36 % ) , patients with existing cardiovascular disease ( 47 % ) , and smokers ( 22 % ) . There were no important differences between the r and omized treatment groups at baseline . ALLHAT will add greatly to our underst and ing of the management of hypertension by providing an answer to the following question : are newer antihypertensive agents similar , superior , or inferior to traditional treatment with diuretics BACKGROUND Frail and polypathological patients ( PP ) are often undertreated with evidence -based cardiovascular drugs , as their benefits are uncertain in this population . OBJECTIVES To determine the effects of treatment with renin-angiotensin system blockers/inhibitors ( ACEI/ARB ) , statins and /or beta-blockers on survival rates and functional decline in PP with evidence -based clinical indications for treatment with any of these drug families . METHOD Prospect i ve observational multicentre cohort study with a 12-month follow-up period . We selected PP with any condition of the following : chronic heart failure , coronary heart disease , chronic renal disease , cerebrovascular disease , peripheral artery disease , diabetes mellitus with any visceral involvement , hypertension , and dyslipidaemia . Clinical , functional ( Barthel index ) , socio-familial risk data and drug prescriptions were measured at baseline . Multivariate Cox proportional hazards and logistic regression models were used to identify variables independently associated with survival and functional decline . RESULTS The analysis included 1260 PP . The mean age was 79±9.5 years . The mortality rate was 34.5 % . Statin ( aHR 0.671 ; P=0.001 ) , beta-blocker plus statin ( aHR 0.645 ; P=0.007 ) , ACEI/ARB plus statin ( aHR 0.680 ; P=0.002 ) , or combined ACEI/ARB plus statin plus beta-blocker ( aHR 0.541 ; P=0.000 ) prescriptions were associated with longer survival times . Additionally , PP whose Barthel index was ≥60 showed a lower risk of disability progression if treated with statins ( aOR=0.476 ; P=0.000 ) , or their combinations , mainly with ACEI/ARB plus beta-blockers ( aOR 0.563 ; P=0.031 ) . CONCLUSIONS The prescription of statins , alone or in combination with other drugs , may impact the survival and functional decline  in polypathological patients . Further prospect i ve blinded r and omised assays are needed to confirm these observations Both myocardial m-[123I]iodobenzylguanidine ( 123I-MIBG ) uptake and plasma norepinephrine are markers of sympathetic activation in heart failure and have been shown to portend a poorer prognosis . However , these observations were noted before treatment with beta blockers became part of st and ard clinical practice . Fifty-eight patients with chronic heart failure ( New York Heart Association functional class II and III , ejection fraction < 35 % ; 53 % ischaemic cardiomyopathy ) were prospect ively studied with a mean follow-up of 36 months . During the observational period , 17 patients ( 29.3 % ) had a predefined event ( death and heart transplantation ) . All prognostic parameters were obtained before beta blocker therapy was initiated . In both uni- and multivariate analysis , the heart-mediastinum ratio of 123I-MIBG uptake did not correlate with cardiovascular mortality . In the multivariate Cox regression analysis , plasma norepinephrine , peak oxygen consumption , end-diastolic volume as measured by echocardiography and exercise performance during bicycling and walking had prognostic significance in patients with heart failure treated with beta blockers in addition to angiotensin-converting enzyme inhibitors BACKGROUND Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs . We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to st and ard therapy for heart failure . METHODS A total of 5010 patients with heart failure of New York Heart Association ( NYHA ) class II , III , or IV were r and omly assigned to receive 160 mg of valsartan or placebo twice daily . The primary outcomes were mortality and the combined end point of mortality and morbidity , defined as the incidence of cardiac arrest with resuscitation , hospitalization for heart failure , or receipt of intravenous inotropic or vasodilator therapy for at least four hours . RESULTS Overall mortality was similar in the two groups . The incidence of the combined end point , however , was 13.2 percent lower with valsartan than with placebo ( relative risk , 0.87 ; 97.5 percent confidence interval , 0.77 to 0.97 ; P=0.009 ) , predominantly because of a lower number of patients hospitalized for heart failure ; 455 ( 18.2 percent ) in the placebo group and 346 ( 13.8 percent ) in the valsartan group ( P<0.001 ) . Treatment with valsartan also result ed in significant improvements in NYHA class , ejection fraction , signs and symptoms of heart failure , and quality of life as compared with placebo ( P<0.01 ) . In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme ( ACE ) inhibitors or beta-blockers , valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs . CONCLUSIONS Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure , when added to prescribed therapy . However , the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan , an ACE inhibitor , and a beta-blocker raises concern about the potential safety of this specific combination Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension . Beta-blockade interacts with heart rate , sympathetic tone , maximal workload and local lactate production . In the present r and omized-controlled study , we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade . Fifty-two patients ( 23 with beta-blocker , 29 without beta-blocker ) ⩾60 years with systolic 24-h ambulatory blood pressure ( ABP ) ⩾140 mm Hg and /or antihypertensive treatment were r and omly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme ( lactate 2.0 mmol/l ) . In the exercise group , the training significantly decreased systolic and diastolic 24-h ABP , blood pressure on exertion ( 100 W ) and increased endothelium-dependent vasodilation ( flow-mediated vasodilation , FMD ) and physical performance both in the presence and absence of beta-blockade ( P<0.05 each ) . The extent of ABP reduction did not significantly differ in the presence or absence of beta-blockade ( Δ systolic ABP 10.6±10.5 vs 10.6±8.8 mm Hg , Δ diastolic ABP 5.7±8.6 vs 5.8±4.0 mm Hg ) . Mean training heart rate was significantly lower in the patients on beta-blockers ( 97.2±7.7 vs 118.3±7.5/min , P<0.001 ) . Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function . In the present study , target training heart rate with beta-blockers is about 18 % lower than without OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society BACKGROUND The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established . We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension . METHODS We did a prospect i ve , r and omised , double-blind trial in Europe and Israel in 6321 patients aged 55 - 80 years with hypertension ( blood pressure > or = 150/95 mm Hg , or > or = 160 mm Hg systolic ) . Patients had at least one additional cardiovascular risk factor . We r and omly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system ( GITS ) formulation ( n=3157 ) , or co-amilozide ( hydrochlorothiazide 25 mg [ corrected ] plus amiloride 2.5 mg ; n=3164 ) . Dose titration was by dose doubling , and addition of atenolol 25 - 50 mg or enalapril 5 - 10 mg . The primary outcome was cardiovascular death , myocardial infa rct ion , heart failure , or stroke . Analysis was done by intention to treat . FINDINGS Primary outcomes occurred in 200 ( 6.3 % ) patients in the nifedipine group and in 182 ( 5.8 % ) in the co-amilozide group ( 18.2 vs 16.5 events per 1000 patient-years ; relative risk 1.10 [ 95 % CI 0.91 - 1.34 ] , p=0.35 ) . Overall mean blood pressure fell from 173/99 mm Hg ( SD 14/8 ) to 138/82 mm Hg ( 12/7 ) . There was an 8 % excess of withdrawals from the nifedipine group because of peripheral oedema ( 725 vs 518 , p<0.0001 ) , but serious adverse events were more frequent in the co-amilozide group ( 880 vs 796 , p=0.02 ) . Deaths were mainly non-vascular ( nifedipine 176 vs co-amilozide 172 ; p=0.81 ) . 80 % of the primary events occurred in patients receiving r and omised treatment ( 157 nifedipine , 147 co-amilozide , difference 0.33 % [ -0.7 to 1.4 ] ) . INTERPRETATION Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications . The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure  , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS CAPPP was a prospect i ve , r and omised , open trial with blinded endpoint evaluation . 10,985 patients were enrolled at 536 health centres in Sweden and Finl and . Patients aged 25 - 66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were r and omly assigned captopril or conventional antihypertensive treatment ( diuretics , beta-blockers ) . Analysis was by intention-to-treat . The primary endpoint was a composite of fatal and non-fatal myocardial infa rct ion , stroke , and other cardiovascular deaths . FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy , 14 and 13 , respectively , were lost to follow-up . Primary endpoint events occurred in 363 patients in the captopril group ( 11.1 per 1000 patient-years ) and 335 in the conventional-treatment group ( 10.2 per 1000 patient-years ; relative risk 1.05 [ 95 % CI 0.90 - 1.22 ] , p=0 - 52 ) . Cardiovascular mortality was lower with captopril than with conventional treatment ( 76 vs 95 events ; relative risk 0.77 [ 0.57 - 1 - 04 ] , p=0.092 ) , the rate of fatal and non-fatal myocardial infa rct ion was similar ( 162 vs 161 ) , but fatal and non-fatal stroke was more common with captopril ( 189 vs 148 ; 1.25 [ 1 - 01 - 1 - 55 ] . p=0.044 ) . INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality . The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients r and omised to conventional therapy OBJECTIVES We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease ( PAD ) . BACKGROUND Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality . Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications . However , the potential benefit of cardiac medication in patients with PAD remains ill defined . METHODS In this prospect i ve observational cohort study , 2,420 consecutive patients ( age , 64 + /- 11 years , 72 % men ) with PAD ( ankle-brachial index < or = 0.90 ) were screened for clinical risk factors and cardiac medication . Follow-up end point was death from any cause . Propensity scores for statins , beta-blockers , aspirin , angiotensin-converting enzyme ( ACE ) inhibitors , calcium channel blockers , diuretics , nitrates , coumarins , and digoxin were calculated . Cox regression models were used to analyze the relation between cardiac medication and long-term mortality . RESULTS Medical history included diabetes mellitus in 436 patients ( 18 % ) , hypercholesterolemia in 581 ( 24 % ) , smoking in 837 ( 35 % ) , hypertension in 1,162 ( 48 % ) , coronary artery disease in 1,065 ( 44 % ) , and a history of heart failure in 214 ( 9 % ) . Mean ankle-brachial index was 0.58 ( + /-0.18 ) . During a median follow-up of eight years , 1,067 patients ( 44 % ) died . After adjustment for risk factors and propensity scores , statins ( hazard ratio [ HR ] 0.46 , 95 % confidence interval [ CI ] 0.36 to 0.58 ) , beta-blockers ( HR 0.68 , 95 % CI 0.58 to 0.80 ) , aspirins ( HR 0.72 , 95 % CI 0.61 to 0.84 ) , and ACE inhibitors ( HR 0.80 , 95 % CI 0.69 to 0.94 ) were significantly associated with a reduced risk of long-term mortality . CONCLUSIONS On the basis of this observational longitudinal study , statins , beta-blockers , aspirins , and ACE inhibitors are associated with a reduction in long-term mortality in patients with PAD In previous beta-blocker trials , post-myocardial infa rct ion ( MI ) patients were essentially treated with a beta-blocker or placebo . In the CAPRICORN trial , patients were selected on the basis of a left ventricular ( LV ) ejection fraction ( EF ) < 40 % following the index MI and r and omised to carvedilol or placebo  , in addition to modern secondary prophylaxis with ACE inhibitors , aspirin and statins .  In 1959 patients with a mean LVEF of 33 % , treatment with carvedilol over a mean follow-up period of 15 months reduced total mortality from 15.3 % with placebo to 11.9 % with carvedilol [ relative risk reduction ( RRR ) = 23 % , absolute risk reduction ( ARR ) = 3.4 % ] . The incidence of recurrent MI was reduced from 5.8 to 2.3 % ( RRR 41 % , ARR 2.3 % ) . The number needed to treat ( NNT ) to prevent one death was 28 for the entire study period and 43 for 1 year of treatment . The results of the CAPRICORN trial are compared with three previous beta-blocker post-MI trials : the Gothenburg metoprolol trial ( GMT ) , the Norwegian timolol trial ( NTT ) and the beta-blocker heart attack trial ( BHAT ) . The RRRs for total mortality were 36 % in the GMT and NTT , and 27 % in BHAT . The respective NNTs for total mortality were 32 , 18 and 38 . NNT for 1 year of treatment was 25 in NTT and 80 in BHAT . The RRR for recurrent MIs were 28 % in NTT and 16 % in BHAT . The reduction of mortality and recurrent MIs in CAPRICORN is within the range of previous post-MI beta-blocker studies . In post-MI patients with LVEF<40 % , add-on treatment with a beta-blocker should be given > 48 h after initiation with an angiotensin-converting enzyme inhibitor ( ACEI ) and then with a slow dose escalation as applied in CAPRICORN BACKGROUND It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications . Because this issue remains controversial , we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were r and omly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study . METHODS The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve , r and omized , blinded trial comparing the effects of moderate control of blood pressure ( target diastolic pressure , 80 to 89 mm Hg ) with those of intensive control of blood pressure ( diastolic pressure , 75 mm Hg ) on the incidence and progression of complications of diabetes . The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes . In the current study , we analyzed data on a secondary end point ( the incidence of myocardial infa rct ion ) in the subgroup of patients in the ABCD Trial who had hypertension . RESULTS Analysis of the 470 patients in the trial who had hypertension ( base-line diastolic blood pressure , > or = 90 mm Hg ) showed similar control of blood pressure , blood glucose and lipid concentrations , and smoking behavior in the nisoldipine group ( 237 patients ) and the enalapril group ( 233 patients ) throughout five years of follow-up . Using a multiple logistic-regression model with adjustment for cardiac risk factors , we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infa rct ions ( a total of 24 ) than enalapril ( total , 4 ) ( risk ratio , 9.5 ; 95 percent confidence interval , 2.7 to 33.8 ) . CONCLUSIONS In this population of patients with diabetes and hypertension , we found a significantly higher incidence of fatal and nonfatal myocardial infa rct ion among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril . Since our findings are based on a secondary end point , they will require confirmation OBJECTIVE To determine whether a third generation vasodilating beta blocker ( celiprolol ) has long term clinical advantages over metoprolol in patients with chronic heart failure . DESIGN A double blind placebo controlled r and omised trial . SETTING University teaching Hospital . PATIENTS 50 patients with stable chronic heart failure ( NYHA class II-IV ) due to idiopathic dilated , ischaemic , or hypertensive cardiomyopathy , with left ventricular ejection fraction < 0.45 . INTERVENTIONS Celiprolol 200 mg daily ( n = 21 ) , metoprolol 50 mg twice daily ( n = 19 ) , or placebo ( n = 10 ) for three months with a four week dose titration period . After the double blind period , patients entered an open label study ( with placebo group receiving beta blockers ) and were assessed after one year . MAIN OUTCOME MEASURES Clinical response , efficacy , and tolerance were assessed by the Minnesota heart failure symptom question naire six minute walk test , Doppler echocardiography ( systolic and diastolic function ) , radionuclide ventriculography , and atrial and brain natriuretic peptides measured at baseline and after three months . RESULTS In the metoprolol group at 12 weeks v baseline there was a 47 % reduction in symptom score ( p < 0.001 ) , improvement of NYHA class ( mean ( SEM ) , 2.6 ( 0.12 ) to 1.9 ( 0.13 ) , p = 0.001 ) , exercise distance ( 1246 ( 54 ) to 1402 ( 52 ) feet , p < 0.001 ) , and left ventricular ejection fraction ( 26.9(3.1)% to 31(3.0)% , p = 0.016 ) , and a fall in heart rate ( resting , 79 ( 3 ) to 62 ( 3 ) beats/min , p < 0.001 ) . In the celiprolol group there was a 38 % reduction in symptom score ( p = 0.02 ) , less improvement in exercise distance ( 1191 ( 55 ) to 1256 ( 61 ) feet , p = 0.05 ) , and no significant changes in NYHA class , left ventricular ejection fraction , or heart rate . Mortality at one year was 11 % in metoprolol and 19 % in the celiprolol group , and symptomatic improvement was maintained in the survivors . CONCLUSIONS Both drugs were well tolerated but the vasodilator properties of celiprolol do not seem to provide any obvious additional benefit in the long term treatment of heart failure OBJECTIVES The primary objective of the International Verapamil SR/Tr and olapril Study ( INVEST ) is to compare the risk for adverse outcomes ( all-cause mortality , nonfatal myocardial infa rct ion [ MI ] or nonfatal stroke ) in hypertensive patients with coronary artery disease ( CAD ) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy .  BACKGROUND Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent , for which reductions in morbidity and mortality are documented from r and omized trials but are less than expected from epidemiologic data . For this reason , recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors . While these agents reduce blood pressure , outcome data from large r and omized trials are lacking , but some case-control data , dominated by short-acting dihydropyridines , suggest an increased risk of cardiovascular events . These studies had method ologic limitations and did not differentiate among calcium antagonist types and formulations . Several studies differentiating among calcium antagonist types and an overview of published r and omized trials show no increased risk with verapamil and suggestion for benefit in CAD patients . METHODS A total of 27,000 CAD patients with hypertension will be r and omized at 1,500 primary care sites to receive either a calcium antagonist-based ( verapamil ) or beta-blocker/diuretic-based ( atenolol/hydrochlorothiazide ) antihypertensive care strategy . The study uses a novel , electronic " paper-less " system for direct on-screen data entry , r and omization and drug distribution from a mail pharmacy linked to the coordination center via the Internet . RESULTS Contract negotiations with the United States and international sites are ongoing . Patients being enrolled are predominantly elderly ( 72 % aged 60 years or older ) men ( 54 % ) , with either an abnormal coronary angiogram or prior MI ( 71 % ) . In addition to hypertension , CAD and elderly age , most patients ( 89 % ) have one or more associated conditions ( diabetes , dyslipidemia , smoking , cerebral or peripheral vascular disease , etc . ) contributing to increased risk for adverse outcome . While 26 % have diabetes , most of these are noninsulin dependent . Using the protocol strategies , target blood pressures ( according to JNC VI ) have been reached in 58 % at the fourth visit , and as expected most ( 89 % ) are requiring multiple antihypertensive drugs . CONCLUSION The design and baseline characteristics of the initial patients recruited for a prospect i ve , r and omized , international , multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews BACKGROUND Beta-blockers in high target doses are recommended for heart failure with reduced ejection fraction ( HFrEF ) but not for preserved ejection fraction ( HFpEF ) . Treatment benefits are often more pronounced in high-risk subgroups , and patients with HFpEF with heart rate ≥70 beats per minute have emerged as such a high-risk subgroup . We examined the associations of high-dose beta-blocker use with outcomes in these patients . METHODS Of the 8462 hospitalized patients with heart failure with ejection fraction ≥50 % in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure ( OPTIMIZE-HF ) registry , 5422 had a discharge heart rate ≥70 beats per minute . Of these , 4537 had no contraindications to beta-blocker use , of which 2797 ( 2592 with dose data ) received prescriptions  for beta-blockers . Of the 2592 , 730 received high-dose beta-blockers , defined as atenolol ≥100 mg/day , carvedilol ≥50 mg/day , metoprolol tartrate or succinate ≥200 mg/day , or bisoprolol ≥10 mg/day , and 1740 received no beta-blockers . Using propensity scores for the receipt of high-dose beta-blockers , we assembled a matched cohort of 1280 patients , balanced on 58 characteristics . RESULTS All-cause mortality occurred in 63 % and 68 % of matched patients receiving high-dose beta-blocker vs no beta-blocker , respectively , during 6 years ( median , 2.8 ) of follow-up ( hazard ratio , 0.86 ; 95 % confidence interval , 0.75 - 0.98 ; P = .027 ) . The hazard ratios ( 95 % confidence intervals ) for all-cause readmission and the combined endpoint of all-cause readmission or all-cause mortality associated with high-dose beta-blocker use were 0.90 ( 0.81 - 1.02 ) and 0.89 ( 0.80 - 1.00 ) , respectively . CONCLUSIONS In patients with HFpEF and heart rate ≥70 beats per minute , high-dose beta-blocker use was associated with a significantly lower risk of death . Future r and omized controlled trials are needed to examine this association Insulin resistance underlies most glucose disorders in adults and is associated with an increased risk of cardiovascular disease . Alpha blockers decrease insulin resistance , whereas diuretics increase insulin resistance . The authors studied the effects of these two classes of hypertension medications ( doxazosin , an a blocker , and chlorthalidone , a diuretic ) on cardiovascular disease outcomes in adults aged > 55 years with hypertension and glucose disorders who were participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial ( 8749 had known diabetes mellitus and 1690 had a newly diagnosed glucose disorder [ fasting glucose > /=110 mg/dL ] ) . There was no difference in either group between the chlorthalidone- and doxazosin-based treatments with regard to fatal or nonfatal myocardial infa rct ion or all-cause mortality . There was , however , a difference for combined cardiovascular disease ( myocardial infa rct ion , revascularization procedures , angina , stroke , heart failure , and peripheral arterial disease ) in favor of the diuretic . This difference was due primarily to an increased heart failure risk in those treated with doxazosin ( relative risk , 1.85 ; 95 % confidence interval , 1.56 - 2.19 ) in the known diabetes mellitus group and a relative risk of 1.63 ( 95 % confidence interval , 1.05 - 2.55 ) in those with a newly diagnosed glucose disorder despite lower glucose levels on follow-up in those treated with a blockers . The authors conclude that treatment of hypertension with doxazosin in adults with glucose disorders incurs the same risk of coronary heart disease as treatment with chlorthalidone ; however , treatment with doxazosin increases the risk of combined cardiovascular disease and heart failure despite lower glucose levels
Atenolol  was the beta‐blocker most used .
Current evidence suggests that initiating treatment of hypertension with beta‐blockers leads to modest CVD reductions and little or no effects on mortality .
These beta‐blocker effects are inferior to those of other antihypertensive drugs .
Abstract Background Beta‐blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties .
They have shown long‐term beneficial effects on mortality and cardiovascular disease ( CVD ) when used in people with heart failure or acute myocardial infa rct ion .
Beta‐blockers were thought to have similar beneficial effects when used as first‐line therapy for hypertension .
However , the benefit of beta‐blockers as first‐line therapy for hypertension without compelling indications is controversial .
This review is an up date of a Cochrane Review initially published in 2007 and up date d in 2012 .
Objectives To assess the effects of beta‐blockers on morbidity and mortality endpoints in adults with hypertension .