Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group. The Eurevie Study: contrasting effect of piretanide and thiazides in mild to moderate hypertension. The Combination of Chlorthalidone with Nifedipine Does Not Exert an Additive Antihypertensive Effect in Essential Hypertensives: A Crossover Multicenter Study Relation between low dose of hydrochlorothiazide, antihypertensive effect and adverse effects. Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. A 10-year controlled trial with bendroflumethiazide. Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT) Factorial antihypertensive study of an extended-release metoprolol and hydrochlorothiazide combination. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. Outcome Results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in Patients With Hypertension and NIDDM 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 The relationship of weight change to changes in blood pressure, serum uric acid, cholesterol and glucose in the treatment of hypertension. Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group. Antihypertensive and biochemical effects of indacrinone enantiomers. South African hypertension guideline 2011. Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP) Effect of allopurinol on blood pressure and aortic compliance in hypertensive patients Serum Lipoproteins During Treatment with the Antihypertensive Agent Indapamide Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) Decreased Coronary Heart Disease in Hypertensive Smokers Mortality Results From the MAPHY Study Dementia risk with antihypertensive use and blood pressure variability A double-blind study of tienilic acid with two year follow-up of patients with mild to moderate essential hypertension. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. 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. Double-blind comparison of indapamide with a placebo in hypertensive patients treated by practicing physicians. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Effect of Sesame Oil on Diuretics or ß-blockers in the Modulation of Blood Pressure, Anthropometry, Lipid Profile, and Redox Status Twenty-four hour ambulatory blood pressure in the International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension–2
BACKGROUND Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors . METHODS The Systolic Hypertension in the Elderly Program was a community-based , multicenter , r and omized , double-blind , placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older . This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program , including changes in serum chemistry test results in a subgroup for 3 years . Patients were r and omized to receive placebo or treatment with active drugs , with the dose increased in stepwise fashion if blood pressure control goals were not attained : step 1 , 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone ; and step 2 , the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo . RESULTS After 3 years , the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group ( both groups , P<.001 ) . New cases of diabetes were reported by 8.6 % of the participants in the active treatment group and 7.5 % of the participants in the placebo group ( P=.25 ) . Small effects of active treatment compared with placebo were observed with fasting levels of glucose ( + 0.20 mmol/L [ + 3.6 mg/dL ] ; P<.01 ) , total cholesterol ( + 0.09 mmol/L [ + 3.5 mg/dL ] ; P<.01 ) , high-density lipoprotein cholesterol ( -0.02 mmol/L [ -0.77 mg/dL ] ; P<.01 ) and creatinine ( + 2.8 micromol/L [ + 0.03 mg/dL ] ; P<.001 ) . Larger effects were seen with fasting levels of triglycerides ( + 0.9 mmol/L [ + 17 mg/dL ] ; P<.001 ) , uric acid ( + 35 micromol/L [ + .06 mg/dL ] ; P<.001 ) , and potassium ( -0.3 mmol/L ; P<.001 ) . No evidence was found for a subgroup at higher risk of risk factor changes with active treatment . CONCLUSIONS Antihypertensive therapy with low-dose chlorthalidone ( supplemented if necessary ) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels UNLABELLED This study compares the loop diuretic piretanide 6 mg in a slow-release formulation ( PIR ) with hydrochlorothiazide 25 mg ( HCT ) and the fixed combination altizide 15 mg-spironolactone 25 mg ( ALT-SP ) in hypertension . 1105 mild to moderate hypertensive patients entered a three-week placebo wash-out period ; 899 were r and omized in a 6-month , double-blind , parallel group treatment phase ; 800 completed the study . Primary end-points ; serum potassium concentration and quality of life at one month ; secondary end-points : ionic , renal and metabolic variables ; blood pressure ( BP ) measurements . HCT and ALT-SP were compared only to PIR using Dunnett 's or chi 2 tests . RESULTS No difference was found for the overall quality of life . No change of serum potassium concentration at one month was found in PIR while small decreases were detected with ALT-SP ( -0.1 mM ) and HCT ( -0.26 mM ) . Serum creatinine concentration increased significantly in ALT-SP when compared to PIR . All the drugs were effective in reducing BP : HCT had a higher rate of responders than PIR with similar mean BP falls and ALT-SP induced greater falls in blood pressure . CONCLUSION PIR proves to be a potent antihypertensive drug without significant effect on serum electrolytes , plasma glucose and lipids . HCT was slightly more potent but induced a fall in serum potassium concentration with a significant risk of hypokalaemia . The addition of SP to ALT led to a more potent diuretic with a higher level of serum potassium and plasma creatinine disturbances To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment , 66 uncomplicated essential hypertensives , whose diastolic blood pressure was > 100 and < 115 mm Hg at the end of a 1-month washout placebo period , received , according to a r and omized , double-blind , crossover design , nifedipine ( 20 mg b.i.d . ) , chlorthalidone ( 25 mg o.d . ) , the two drugs combined at the same doses , and the corresponding placebo . When compared to the r and omized placebo the three active treatments significantly ( p < 0.001 ) reduced blood pressure without changing heart rate and body weight . However , blood prssure values were similarly reduced under nifedipine and the combination and were significantly lower ( p < 0.05 ) than those under chlorthalidone . Moreover , the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly ( normalized , p < 0.001 ; responders , p < 0.02 ) greater than those under chlorthalidone . Under chlorthalidone and its combination with nifedipine , plasma potassium tended to decrease and blood glucose and serum uric acid were significantly ( p < 0.05 ) increased . These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid . Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives Thiazide diuretics are widely used in the drug treatment of hypertension but their dose-response curves for the antihypertensive and adverse metabolic effects differ . To characterize the lower end of the dose-response curve a double-blind , parallel group trial was performed as multicentre study in Sc and inavia . One hundred and eleven patients with newly diagnosed or previously treated mild to moderate hypertension ( untreated diastolic blood pressure of 95 - 115 mmHg after 4 weeks placebo ) were r and omly allocated to various doses of hydrochlorothiazide ( 3 , 6 , 12.5 or 25 mg ) or placebo for 6 weeks . Blood pressure and biochemical variables ( plasma renin activity , serum potassium , magnesium , urate , fasting glucose , total cholesterol , HDL-cholesterol , triglycerides and apolipoproteins A1 and B were measured . 12.5 mg hydrochlorothiazide had a borderline effect on blood pressure whilst 25 mg had a definite antihypertensive effect . Biochemical changes were seen in plasma renin activity , serum potassium and urate after the 12.5 and 25 mg dose . Three and 6 mg had no effect on blood pressure or metabolic parameters Blood pressure ( BP ) and metabolic variables were determined initially and after 1 , 2 , 4 , 6 and 10 years ' treatment in two groups of hypertensive men ( n = 53 each ) r and omized to bendroflumethiazide 2.5 - 5 mg/day or propranolol 160 - 320 mg daily . There was no significant differences in BP or metabolic variables between the two groups at entry . BP was reduced to the same degree by both treatments . Five men in the propranolol group and one man in the thiazide group developed clinical ly overt diabetes during follow-up . Fasting blood sugar increased slightly but significantly though equally in both groups . Oral glucose tolerance was initially impaired to the same degree in both groups but improved significantly during treatment with both drugs . Fasting insulin increased slightly but to the same degree . While serum potassium decreased significantly in the thiazide group , the total body potassium was unchanged in this group . In the propranolol group , serum potassium rose , while total body potassium decreased significantly . Serum urate increased in both groups , though slightly more during thiazide treatment . One case of gout was found in each group . There was no difference in serum lipids between the two groups . The finding in this long-term trial indicate that in middle-aged men with mild to moderate hypertension a low-dose thiazide diuretic like bendroflumethiazide is as effective and safe an antihypertensive agent as the beta-blocker propranolol is and that it does not induce diabetes . The total clinical picture favors the retention of thiazide diuretics as a first choice drug in hypertension Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs In a r and omized primary prevention trial including 3,234 men with mild to moderate uncomplicated hypertension , the effect of the beta-blocker metoprolol or a thiazide diuretic as an initial antihypertensive therapy was compared regarding the risk of sudden cardiovascular death during a follow-up ranging from 2.3 to 10.8 years ( median of 4.2 years ) . Only men aged 40 to 64 years were included in the study . The r and omization of patients into the metoprolol ( n = 1,609 ) or diuretic group ( n = 1,625 ) was performed after stratification for age , smoking habits , serum cholesterol , and systolic blood pressure . At baseline the two treatment groups were well matched . Metoprolol was given in a mean dose of 174 mg daily and the mean dose of thiazide diuretic was either 46 mg hydrochlorothiazide daily or 4.4 mg bendroflumethiazide daily . Identical blood pressure control was achieved using the fixed therapeutic schedule . Total and cardiovascular mortality were significantly lower for metoprolol than for diuretics , owing to fewer deaths from coronary heart disease and stroke . Of the cardiovascular deaths , 78 % were classified as sudden cardiovascular deaths ( occurred within 24 h after the onset of symptoms ) . There were significantly fewer sudden cardiovascular deaths in the metoprolol group compared to the diuretic group ( 32 v 45 , P = .017 ) . The present results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of sudden cardiovascular deaths than initial diuretic treatment in uncomplicated hypertension 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 To attain goal blood pressure ( BP ) , many hypertensive patients require combination antihypertensive therapy . Thiazide diuretic/beta-blocker regimens lower BP , and clinical studies indicate that they reduce the risk for cardiovascular consequences of hypertension . Fixed-dose combination tablets can simplify multidrug treatment regimens . METHODS This multicenter , r and omized , double-blind , placebo-controlled , unbalanced factorial study ( N = 1571 ) was design ed to determine whether hydrochlorothiazide ( HCT ) and extended release ( ER ) metoprolol both contribute to an antihypertensive effect .  Hypertensive adults with sitting diastolic BP ( SiDBP ) 95 to 114 mm Hg and systolic BP ( SiSBP ) < 180 mm Hg received one of three hydrochlorothiazide doses ( 6.25 mg , 12.5 mg , or 25 mg ) , one of four ER-metoprolol doses ( 25 mg , 50 mg , 100 mg , 200 mg ) , or one of nine of the combinations or placebo for 8 weeks . RESULTS Blood pressure decreased with all combinations ( P < .001 v placebo ) ; reductions were dose related , ranging from 8.7 to 15.7 mm Hg ( SiDBP ) and 9.7 to 18.9 mm Hg ( SiSBP ) ( model-derived values ) . Reductions with placebo were 5.3 ( SiDBP ) and 4.2 mm Hg ( SiSBP ) . Both active agents contributed to the combination effect ( P = .0015 for SiDBP ; P = .0006 for SiSBP ) . Several low-dose combinations were approximately as effective as high doses of the individual agents ( differences within 1 to 2.5 mm Hg ) . The adverse event discontinuation rate was 2.9 % . Serum potassium decreased and uric acid increased with increasing doses of HCT . CONCLUSIONS Extended-release metoprolol/hydrochlorothiazide is an effective antihypertensive combination that offers additive antihypertensive contributions from both components 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 OBJECTIVE ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism . The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events R and omized Trial ( FACET ) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension . Prospect ively defined cardiovascular events were assessed as secondary outcomes . RESEARCH DESIGN AND METHODS Inclusion criteria included a diagnosis of NIDDM and hypertension ( systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg ) . Exclusion criteria included a history of coronary heart disease or stroke , serum creatinine > 1.5 mg/dl , albuminuria > 40 μg/min , and use of lipid-lowering drugs , aspirin , or antihypertensive agents other than beta-blockers or diuretics . A total of 380 hypertensive diabetics were r and omly assigned to open-label fosinopril ( 20 mg/day ) or amlodipine ( 10 mg/day ) and followed for up to 3.5 years . If blood pressure was not controlled , the other study drug was added . RESULTS Both treatments were effective in lowering blood pressure . At the end of followup , between the two groups there was no significant difference in total serum cholesterol , HDL cholesterol , HbA1c , fasting serum glucose , or plasma insulin . The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infa rct ion , stroke , or hospitalized angina than those receiving amlodipine ( 14/189 vs. 27/191 ; hazards ratio = 0.49 , 95 % CI = 0.26–0.95 ) . CONCLUSIONS Fosinopril and amlodipine had similar effects on biochemical measures , but the patients r and omized to fosinopril had a significantly lower risk of major vascular events , compared with the patients r and omized to amlodipine 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 In the Hypertension Detection and Follow-up Program ( HDFP ) , elevated blood pressure ( BP ) was treated by rigorous , stepped care ( SC ) therapy among half the participants , while the other half were referred to usual sources of care ( referred care , RC ) . There was no program to reduce weight , however , some participants changed weight voluntarily over the first 2 yr , providing an opportunity to examine the role of weight change in the development of diuretic-induced hyperuricemia , hyperglycemia and hypercholesterolemia . There was a stepwise progression from decreased glucose , uric acid and cholesterol concentrations , and BP associated with maximum weight loss to increased values with maximum weight gain . In SC , systolic BP declined by 22.4 % among weight-losers and by 17.1 % among weight-gainers ; in RC , it was 14.4 and 8.1 % , respectively . The pattern in diastolic blood pressure and weight change was similar but not as marked . These findings suggest the potential importance of weight loss in enhancing effectiveness of antihypertensive drug treatment and attenuating increases in glucose , uric acid , and cholesterol associated with diuretic treatment of hypertension . The weight change analyses are based on postr and omization observations and do not reflect experimental changes To achieve the target blood pressure recommended by the latest guidelines , multiple antihypertensive drugs are needed in most patients . In this study , the efficacy of treatment using an angiotensin II receptor antagonist ( ARB ) combined with a calcium channel blocker ( CCB ) or a diuretic was compared from multiple perspectives in patients with hypertension . Twenty-nine patients with essential hypertension , who had failed to achieve their target blood pressure ( < 130/85 mm Hg for patients < 65 years old and < 140/90 mm Hg for those ⩾65 years ) when treated with the ARB olmesartan at 20 mg day−1 , were additionally given 8–16 mg day−1 of the CCB azelnidipine or 1–2 mg day−1 of trichlormethiazide ( a thiazide diuretic ) in a r and omized crossover manner for 4 months each . At the end of each combination therapy period , blood and urine sample s were collected and arterial stiffness was evaluated by measuring the cardio-ankle pulse wave velocity . Compared with monotherapy , the blood pressure was reduced similarly by adding azelnidipine ( −12/−10 mm Hg ) or trichlormethiazide ( −14/−9 mm Hg ) . The heart rate was decreased with the CCB by 4 b.p.m . ( P<0.05 ) , whereas it was unchanged with the thiazide . Serum K , lipids and blood glucose were not significantly changed with either combination , whereas serum uric acid was increased with the thiazide ( P<0.01 ) but was unchanged with azelnidipine  . Plasma levels of renin , angiotensin II and aldosterone were also increased with the thiazide period , whereas high-sensitivity C-reactive protein and oxidized low-density lipoprotein were decreased with azelnidipine . In addition , the cardio-ankle vascular index , a parameter of arterial stiffness , was decreased with the azelnidipine period but was unchanged with the thiazide period ( P<0.01 ) . It is suggested that the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and a thiazide with respect to avoiding hyperuricemia , sympathetic activation , renin – angiotensin-aldosterone system stimulation , inflammation , oxidative stress , and increased arterial stiffness in patients with moderate hypertension . These properties may provide cardiovascular protection in addition to the hypotensive effect Because obesity-associated hypertension has unique hemodynamic and hormonal profiles , certain classes of antihypertensive agents may be more effective than others as monotherapy . Thus , we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week , multicenter , double-blind trial in 232 obese patients with hypertension . Patients with an office diastolic pressure between 90 and 109 mm Hg were r and omized to treatment with daily doses of lisinopril ( 10 , 20 , or 40 mg ) ,  hydrochlorothiazide  ( 12.5 , 25 , or 50 mg ) , or  placebo . Mean body mass indexes were similar for all patients . At week 12 , lisinopril and hydrochlorothiazide effectively lowered office diastolic ( -8.3 and -7.7 versus -3.3 mm Hg , respectively ; P<.005 ) and systolic ( -9.2 and -10.0 versus -4.6 mm Hg , respectively ; P<.05 ) pressures compared with placebo .  Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo ( P<.001 ) . Significant dose-response differences were observed between treatments . Sixty percent of patients treated with lisinopril had an office diastolic pressure < 90 mm Hg compared with 43 % of patients treated with hydrochlorothiazide ( P<.05 ) . Responses to therapies differed with both race and age . Neither treatment significantly affected insulin or lipid profiles ; however , plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril ( + 0.31 versus -0.21 mmol/L ; P<.001 ) . Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline . In conclusion , lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension . Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics , may have a more rapid rate of response , and may offer advantages in patients at high risk of metabolic disorders 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 enantiomers of indacrinone ( I ) , an investigational loop diuretic , have different pharmacologic activity . The ( - ) enantiomer is natriuretic , and the ( + ) enantiomer is uricosuric . To determine the antihypertensive effects and an isouricemic ratio of indacrinone enantiomers , 37 patients with sitting diastolic blood pressure ( BP ) between 90 and 104 mm Hg , after a 4-week placebo washout , r and omly received one of the ratios of I enantiomers , namely -2.5/+80 mg ( A ) , -5/+80 mg ( B ) , -10/+80 mg ( C ) or placebo ( P ) , once daily for 12 weeks in a double-blind , parallel study . The mean reductions ( baseline-end of treatment ) in BP of 23/8 , 20/10 and 25/10 mm Hg with treatments A , B and C respectively were greater ( p less than 0.01 ) than that on P ( 0/3 ) . Initially , serum uric acid decreased with treatments A and B but not with C. Mean changes in serum uric acid were -0.3 , -0.4 , 0.2 and 0.3 mg/dl respectively with treatments A , B , C and P. The ratio of -10/+80 mg produced least variation in serum uric acid . Reduction in serum K+ and Cl- appeared to be dose related to ( - ) enantiomer . No serious adverse effects were reported . A 1:9 ratio of I enantiomers intended for wide-scale use as a diuretic also showed good antihypertensive activity , a favorable uric acid profile and absence of hepatic toxicity in 14 patients 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 Objective To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with  cardiovascular events in hypertensive patients . Design Cohort study in a r and omized trial . Setting Cohort of hypertensive patients . Participants A total of 4327 men and women , aged ≥ 60 years , with isolated systolic hypertension , r and omized to placebo or chlorthalidone  , with the addition of atenolol or reserpine if needed , were observed for 5 years . Main outcome measures Major cardiovascular events , coronary events , stroke and all-cause mortality . Results Cardiovascular event rates for quartiles of baseline serum uric acid were : I , 32.7 per 1000 person-years ; II , 34.5 per 1000 person-years ; III , 38.1 per 1000 person-years ; and IV , 41.4 per 1000 person-years ( P for trend = 0.02 ) . The adjusted hazard ratio ( HR ) , of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 ( 95 % CI , 1.03–1.69 ) . The benefit of active treatment was not affected by baseline serum uric acid . After r and omization , an increase of serum uric acid < 0.06 mmol/l ( median change ) in the active treatment group was associated with a HR of 0.58 ( 0.37–0.92 ) for coronary events compared with those with a serum uric acid increase ≥ 0.06 mmol/l . This difference was not explained by blood pressure effects . Those with a serum uric acid increase ≥ 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group . Conclusions Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension . Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment Abstract Background . Arterial hypertension is commonly associated with hyperuricemia . Several studies have shown that allopurinol reduces arterial blood pressure in animal models and in adolescent patients with newly diagnosed hypertension . Moreover , allopurinol has shown beneficial effects on endothelial function and arterial wave reflection in contrast to uricosuric agents . Antihypertensive drugs produce different effects on serum uric acid levels . Objective . The aim of the study was to evaluate the influence of allopurinol on blood pressure and aortic compliance in patients with arterial hypertension depending on hypotensive therapy with angiotensin-converting enzyme inhibitor ( ACE-I ) or thiazide diuretic , hypotensive drugs with distinct effects on serum uric acid levels and conversely , a positive influence on pulse wave velocity ( PWV ) in the aorta . Material and Methods . Sixty-six patients aged 25–70 ( mean age 46.17 ± 10.89 ) with mild and moderate arterial hypertension diagnosed on the basis of office blood pressure , were studied . They were r and omized to antihypertensive therapy on either perindopril ( n = 35 ) or hydrochlorothiazide ( n = 31 ) . After 8 weeks of antihypertensive therapy , 150 mg of allopurinol daily was added for the next 8 weeks . Measurement of the serum uric acid level , PWV and 24-h ambulatory blood pressure monitoring ( ABPM ) were performed at baseline , after 8 weeks antihypertensive therapy and again after the final 8 weeks with the additional allopurinol . Results . No significant changes in systolic ( SBP ) and diastolic blood pressure ( DBP ) or ABPM were observed after allopurinol treatment in either of the subgroups receiving ACE-I or thiazide-based antihypertensive therapy . The mean PWV decreased from 10.7 ± 1.4 m/s to 10.0 ± 1.2 m/s ( p = 0.00008 ) in the ACE-I-based therapy subgroup and from 11.5 ±1.7 m/s to 10.4 ± 1.5 m/s ( p = 0.00002 ) in the thiazide-based therapy subgroup after treatment with allopurinol . However , significant correlations were found between PWV changes and the basic PWV ( r = −0.52 ; p < 0.001 ) or SBP changes ( r = 0.29 ; p < 0.019 ) after allopurinol treatment . Conclusions . Allopurinol does not produce additional antihypertensive effects in patients with treated arterial hypertension . Allopurinol increases aortic compliance independently of ACE-I or thiazide-based , antihypertensive therapy . However , this effect is significantly dependent on the initial PWV in the aorta and on SBP changes during allopurinol therapy Considering the documented , potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins , we prospect ively investigated in 69 men(mean age ± SEM , 32 ± 1 years ) the metabolic effects of the new diuretic-antihypertensive compound indapamide . Compared to placebo , indapamide ( 2.5 mg/day ) given for 6 to 8 weeks lowered ( p < 0.02 to < 0.001 ) blood pressure(supine values from 148/98 ± 3/2 to 137/93 ± 3/2 ) in 29 men with mild to moderate essential hypertension , but not in 40 healthy men . In both groups , significant ( p < 0.05 to < 0.001 ) decreases in body weight ( −0.8 kg ) and plasma potassium ( −0.6 mmol/L ) , and increases in plasma uric acid (= 20 % ) , renin activity (= 200 % ) , and aldosterone documented good compliance . There were no significant changes hi total cholesterol(in all subjects , from 208 ± 6 to 213 ± 6 mg/dl ) , low- or very low-density lipoprotein(VLDL ) cholesterol ( 127 ± 6 to 129 ± 6 and 21 ± 1 to 21 ± 2 respectively ) , high-density lipoprotein cholesterol ( 50 ± 1 to 51 ± 1 mg/dl ) , total triglycerides(Tg ) ( 108 ± 5 to 112 ± 6 mg/dl ) , VLDL-Tg , apoproteins Al and A2 , plasma glucose , epinephrine , norepinephrine , sodium , calcium , magnesium , and creatinine ; apoprotein B ( 84 ± 2 to 88 ± 3 mg/dl ) and plasma insulin after glucose loading dose tended to be increased minimally . The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.(Hypertension 7 [ Suppl II ] : II-164–II-169 , 1985 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 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 Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality The present primary prevention study aim ed at investigating whether metoprolol given as initial antihypertensive treatment would lower cardiovascular complications of high blood pressure to a greater extent than thiazide diuretics .  Patients were r and omized to metoprolol ( n = 1,609 , 8,110 patient-years ) or a thiazide diuretic ( n = 1,625 , 8,070 patient-years ) . At r and omization , 535 patients in the metoprolol group and 524 patients in the diuretic group were classified as smokers . Blood pressure control during follow-up was equally effective regardless of smoking habits at r and omization . Cardiovascular and coronary heart disease mortality was three to four times higher in smokers than in nonsmokers , underlining the importance of smoking as a risk factor . Total and cardiovascular mortality were significantly lower for the metoprolol group than for the thiazide diuretic group in the whole study population ( p = 0.028 and p = 0.012 ) , as well as in smokers ( p = 0.013 and p = 0.016 ) . Coronary heart disease mortality was significantly lower for patients on metoprolol  than for patients on diuretics  in the whole study population ( p = 0.048 ) as well as in smokers ( p = 0.02l ) . The results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of total , cardiovascular , and coronary heart disease mortality as compared with initial diuretic treatment , both in the whole study population and in smokers . The favorable effect of metoprolol must be mediated via mechanisms other than the blood pressure-lowering effect of metoprolol because equal blood pressure control was achieved with both types of medication , irrespective of smoking habits at r and omization Objective : To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability ( BPV ) in the preceding 4 years . Methods : A total of 6,537 participants ( mean age 79 years , 62 % women ) in a prospect i ve population -based cohort were followed up for incident dementia . A 4-year time lag period was created to classify drug exposure and measure blood pressure . BPV ( percent coefficient of variation [ CV ] ) was regressed against 9 antihypertensive drug classes ( BPVreg ) . Cox regression models were employed to determine hazard ratios ( HRs ) for incident dementia thereafter according to drug class , adjusted for mean blood pressure , covariates , and BPV or BPVreg . Results : Over a median 8.4 years follow-up ( interquartile range 6.7–9.0 ) , lower dementia risk was associated with nondihydropyridine calcium channel blocker ( HR 0.56 ; 95 % confidence interval [ CI ] 0.31–1.00 , p = 0.05 ) and loop diuretics ( HR 0.45 ; 95 % CI 0.22–0.93 , p = 0.03 ) after adjusting for CV-BPV . Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker ( HR 0.52 ; 95 % CI 0.28–0.95 , p = 0.03 ) and loop diuretics ( HR 0.40 ; 95 % CI 0.19–0.83 , p = 0.01 ) . All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05 . Conclusions : Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years . Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk In a double-blind study , thirty patients having mild to moderate essential hypertension were r and omly assigned to a six week regimen of either tienilic acid , hydrochlorothiazide , or placebo .  Blood pressure was significantly reduced with tienilic acid and hydrochlorothiazide although more so with tienilic acid .  Serum uric acid declined strikingly with tienilic acid and increased significantly with hydrochlorothiazide .  Serum potassium declined slightly with tienilic acid but more so with hydrochlorothiazide .  Serum creatinine and blood urea nitrogen increased slightly more with tienilic acid than with hydrochlorothiazide . There were no clinical adverse effects to any of the medications during this study . Twenty-four months of continuous administration of tienilic acid revealed maintenance of blood pressure effect , but with slight increases in blood urea nitrogen , serum creatinine and uric acid and slight decreases in serum potassium as compared to six weeks administration . Tienilic acid appears to be a useful new antihypertensive agent . The hypouricaemic effect is profound and strongly suggests the need for continuing evaluation of this compound because of its unique combination of diuretic , antihypertensive and hypouricaemic properties The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal 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 The antihypertensive effect of indapamide ( 2.5 mg/day ) was compared to that obtained with a placebo in a controlled trial carried out by 11 physicians in their private practice . Thirty-one patients with uncomplicated essential hypertension were included . After a run-in period of 3 weeks without any treatment , either indapamide ( n = 16 ) or a placebo ( n = 15 ) were administered for 8 weeks in double-blind fashion . Blood pressure decreased in both groups . In patients treated with indapamide , systolic pressure was significantly lower than in those given the placebo at 3 out of the 4 follow-up visits ; diastolic pressure , however , was significantly lower only at the end of the trial . Both the active drug and the placebo were well tolerated . No significant change in body weight , plasma potassium and uric acid occurred during the study in either group of patients . It appears therefore that indapamide , at a dose which apparently has no major diuretic effect , may be useful for practitioners in managing patients with mild to moderate hypertension OBJECTIVE To assess the effect of low-dose , diuretic-based antihypertensive treatment on major cardiovascular disease ( CVD ) event rates in older , non-insulin-treated diabetic patients with isolated systolic hypertension ( ISH ) , compared with nondiabetic patients . DESIGN Double-blind , r and omized , placebo-controlled trial : the Systolic Hypertension in the Elderly Program ( SHEP ) . SETTING Multiple clinical and support centers in the United States . PARTICIPANTS A total of 4736 men and women aged 60 years and older at baseline with ISH ( systolic blood pressure [ BP ] , > or = 160 mm Hg ; diastolic BP , < 90 mm Hg ) at baseline , 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients ( 4 additional patients not so classifiable were r and omized but not included in these analyses ) . Diabetes mellitus defined as physician diagnosis , taking oral hypoglycemic drugs , fasting glucose level of 7.8 mmol/L or more ( > or = 140 mg/dL ) , or any combination of these characteristics . INTERVENTION The active treatment group received a low dose of chlorthalidone ( 12.5 - 25.0 mg/d ) with a step-up to atenolol ( 25.0 - 50.0 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed . The placebo group received placebo and any active antihypertensive drugs prescribed by patient 's private physician for persistently high BP . MAIN OUTCOME MEASURES The 5-year rates of major CVD events , nonfatal plus fatal stroke , nonfatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) , major CHD events , and all-cause mortality . RESULTS The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients , with few adverse effects . For both diabetic and nondiabetic patients , all outcome rates were lower for participants r and omized to the active treatment group than for those r and omized to the placebo group . Thus , 5-year major CVD rate was lower by 34 % for active treatment compared with placebo , both for diabetic patients ( 95 % confidence interval [ CI ] , 6%-54 % ) and nondiabetic patients ( 95 % CI , 21%-45 % ) . Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients ( 101/1000 vs 51/1000 r and omized participants at the 5-year follow-up ) , reflecting the higher risk of diabetic patients . CONCLUSION Low-dose diuretic-based ( chlorthalidone ) treatment is effective in preventing major CVD events , cerebral and cardiac , in both non-insulin-treated diabetic and nondiabetic older patients with ISH In a double blind placebo controlled r and omised parallel study the antihypertensive activity and adverse biochemical effects of three doses of cyclopenthiazide were evaluated in patients with mild essential hypertension that had been recently diagnosed or was being treated with a single drug . After a four week placebo washout period 53 patients with diastolic blood pressures between 90 - 110 mm Hg were r and omly assigned to 50 , 125 , or 500 micrograms cyclopenthiazide or matching placebo for an eight week period of treatment . Blood pressure was measured in the patients ' homes by the same observer every two weeks . Serum urea , electrolytes , urate , and creatinine concentrations and 24 hour urinary sodium excretion were monitored every four weeks and serum magnesium concentration and plasma renin activity at the end of the washout and treatment periods . After eight weeks of treatment systolic and diastolic blood pressures were significantly reduced in patients taking 125 and 500 micrograms cyclopenthiazide when compared with those taking placebo . The decrement in serum potassium concentration ( 0.6 mmol/l ) and increase in serum urate concentration 0.06 mmol/l ) were greatest with the 500 micrograms dose , the increase in serum urate concentration alone being significant . No change in serum magnesium concentration or 24 hour urinary sodium excretion was noted with any dose of cyclopenthiazide . Only the 500 micrograms dose of cyclopenthiazide significantly increased the mean plasma renin activity ( 1.8 ( 95 % confidence interval 0.2 to 3.4)-5.4 ( 3.9 to 6.8 ) nmol angiotensin I/l/h ) ; the other doses like the placebo had no effect . Cyclopenthiazide 125 micrograms , a dose lower than is currently marketed , produced a similar hypotensive response to 500 micrograms of the drug without up setting the biochemical profile 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 The study was undertaken to investigate the effect of sesame oil in hypertensive patients who were on antihypertensive therapy either with diuretics ( hydrochlorothiazide ) or ß-blockers ( atenolol ) . Thirty-two male and 18 female patients aged 35 to 60 years old were supplied sesame oil ( Idhayam gingelly oil ) and instructed to use it as the only edible oil for 45 days . Blood pressure , anthropometry , lipid profile , lipid peroxidation , and enzymic and non-enzymic antioxidants were measured at baseline and after 45 days of sesame oil substitution . Substitution of sesame oil brought down systolic and diastolic blood pressure to normal . The same patients were asked to withdraw sesame oil consumption for another 45 days , and the measurements were repeated at the end of withdrawal period . Withdrawal of sesame oil substitution brought back the initial blood pressure values . A significant reduction was noted in body weight and body mass index ( BMI ) upon sesame oil substitution . No significant alterations were observed in lipid profile except triglycerides . Plasma levels of sodium reduced while potassium elevated upon the substitution of sesame oil .  Lipid peroxidation ( thiobarbituric acid reactive substances [ TBARS ] ) decreased while the activities of superoxide dismutase ( SOD ) , catalase ( CAT ) , and the levels of vitamin C , vitamin E , ß-carotene , and reduced glutathione ( GSH ) were increased . The results suggested that sesame oil as edible oil lowered blood pressure , decreased lipid peroxidation , and increased antioxidant status in hypertensive patients Objectives The International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment ( INSIGHT ) showed , by means of office blood pressure measurements , that long-term treatment with nifedipine GITS is as effective as diuretics in preventing cardiovascular and cerebrovascular complications . However , since office blood pressure measurements reflect to a limited extent blood pressure outside the office , a side-arm INSIGHT study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring was also performed . Design and methods The study had a r and omized , double-blind , parallel group design . After 4 weeks of placebo , mild-to-moderate essential hypertensive patients were r and omized to nifedipine GITS 30 mg or amiloride 2.5 + hydrochlorothiazide  5 mg for 3.1 years . Dose titration was performed by dose doubling and addition of atenolol 25–50 mg or enalapril 5–10 mg , or other drugs when needed . Analysis was carried out by intention-to-treat and included computation of 24 h , day and night ambulatory blood pressure and heart rate values . Additional analyses included computation of the trough-to-peak ratio and the smoothness index ( the ratio between the average of the 24-hourly blood pressure reductions after treatment and its st and ard deviation ) . Results A total of 151 patients were recruited and 149 were valid for analysis : 78 patients had 24 h ambulatory recordings both at baseline and during treatment and 134 during treatment . Office , 24 h and day and night blood pressures were all significantly and similarly reduced by both treatments . Office and ambulatory heart rate was left unchanged by diuretics , while it was slightly reduced by nifedipine . Median trough-to-peak ratios were always > 0.5 and superimposable between the two treatment groups . Similarly , smoothness indices of systolic and diastolic blood pressures were comparably high for nifedipine and diuretics , thus demonstrating a similar well-balanced antihypertensive response to both drugs . No significant differences were observed between the two treatment groups in the number of cardiovascular events ( 17 in the nifedipine-based and 26 in the diuretics-based treatment group ) . Conclusions In the INSIGHT study , the long-term antihypertensive effect on 24 h blood pressure and the cardiovascular protection of nifedipine was similar to that of diuretics CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P<.001 ) groups compared with chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P<.001 ) . For amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy 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
We found no clinical ly meaningful blood pressure-lowering differences between different drugs within the loop diuretic class .
BACKGROUND Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity .
Loop diuretics are indicated and used to treat hypertension , but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from r and omized controlled trial ( RCT ) evidence has not been conducted .
OBJECTIVES To determine the dose-related decrease in systolic or diastolic blood pressure , or both , as well as adverse events leading to participant withdrawal and adverse biochemical effects ( serum potassium , uric acid , creatinine , glucose and lipids profile ) due to loop diuretics versus placebo control in the treatment of people with primary hypertension .