Lack of difference between nebivolol/hydrochlorothiazide and metoprolol/hydrochlorothiazide on aortic wave augmentation and central blood pressure Differential Effects of Nebivolol and Metoprolol on Central Aortic Pressure and Left Ventricular Wall Thickness Effect of different antihypertensive drug classes on central aortic pressure. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Initial blood pressure as a predictor of the response to antihypertensive therapy. Changes in aortic pulse wave velocity in hypertensive postmenopausal women: comparison between a calcium channel blocker vs angiotensin receptor blocker regimen. A comparison of atenolol and nebivolol in isolated systolic hypertension Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients. Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness. South African hypertension guideline 2011. Dementia risk with antihypertensive use and blood pressure variability The efficacy and tolerability of nebivolol in hypertensive African American patients. Antihypertensive medication use and risk of cognitive impairment Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication Efficacy of Combination Antihypertensive Therapy with Low-Dose Indapamide: Assessment by Blood Pressure Self-Monitoring at Home Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice Different drug classes have variable effects on blood pressure depending on the time of day. Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Effects of β blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke Efficacy of losartan and carvedilol on central hemodynamics in hypertensives: a prospective, randomized, open, blinded end point, multicenter study QUALITY OF LIFE BEFORE AND DURING ANTIHYPERTENSIVE TREATMENT: A COMPARATIVE STUDY OF CELIPROLOL AND ATENOLOL Assessment of blood pressure during naproxen therapy in hypertensive patients treated with nicardipine. A new approach to assessing antihypertensive therapy: effect of treatment on pulse pressure. Candesartan cilexetil in Hypertension Ambulatory Measurement of Blood Pressure (CHAMP) Study Investigators. Influence of dietary modifications on the blood pressure response to antihypertensive medication. Hemodynamic and central blood pressure differences between carvedilol and valsartan added to lisinopril at rest and during exercise stress. Effects of azilsartan compared to other angiotensin receptor blockers on left ventricular hypertrophy and the sympathetic nervous system in hemodialysis patients. Partial regression of vascular structural alterations in hypertensive patients treated with alpha-beta-blocker, labetalol. Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Effect of Carvedilol on Ambulatory Blood Pressure, Renal Hemodynamics, and Cardiac Function in Essential Hypertension
Background : The vasodilating beta-blocker nebivolol is thought to be superior in lowering wave reflection and central blood pressure ( BP ) compared to nonvasodilating beta-blockers . The results from studies comparing nebivolol with either metoprolol or atenolol , with or without hydrochlorothiazide ( HCTZ ) , are not unequivocal . Methods : We examined the effects of nebivolol 5 mg and metoprolol 100 mg with HCTZ 12.5 mg on aortic wave augmentation , central BP and hemodynamics using a r and omized , double-blind , crossover design . We included 22 patients ( 17 men , age 59.9 ± 6.4 years ) with office SBP of 155 ± 16 mmHg and DBP of 93 ± 10 mmHg .  Radial applanation tonometry and noninvasive , continuous finger arterial BP measurement was performed at baseline and after 4 weeks of treatment with either drug regimen , separated by a 4-week washout period . Results : Neither treatment affected aortic wave augmentation significantly . Augmentation index increased 1.0 ± 7.8 % ( P = 0.5 ) for nebivolol/HCTZ and 2.4 ± 6.6 % ( P = 0.07 ) for metoprolol/HCTZ . Nebivolol/HCTZ lowered central SBP by 15.8 ± 14.9 mmHg and DBP 10.5 ± 8.4 mmHg , and with metoprolol/HCTZ by 13.5 ± 12.3 mmHg for SBP and 9.5 ± 6.8 mmHg for DBP ( all P < 0.001 ) . Heart rate was lowered 8.1 ± 5.4 beats/min by nebivolol/HCTZ and 8.6 ± 4.9 beats/min by metoprolol/HCTZ . Peripheral BP was reduced to a similar extent as central BP . Peripheral BP decreased by 16.3 ± 14.9 mmHg systolic and 10.1 ± 8.2 mmHg diastolic with nebivolol/HCTZ , and by 15.2 ± 13.0 mmHg systolic and 9.1 ± 6.9 mmHg diastolic with metoprolol/HCTZ . Both treatment modalities had a similar effect on stroke volume , cardiac output , left-ventricular contractility and peripheral resistance . Conclusion : Nebivolol was not superior to metoprolol in reducing aortic wave augmentation or central BP when combined with HCTZ The aim of this study was to investigate the effects of the vasodilating & bgr;-blocker nebivolol and the cardioselective & bgr;-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness . We conducted a r and omized , double-blind study on 80 hypertensive patients . The patients received either 5 mg of nebivolol or 50 to 100 mg of metoprolol succinate daily for 1 year . Their heart rate , central and brachial blood pressures , mean arterial pressure , augmentation index , carotid-femoral pulse wave velocity , and left ventricular wall thickness were measured at baseline and at the end of the study . Nebivolol and metoprolol significantly reduced heart rate , brachial blood pressure , and mean arterial pressure to the same degree . However , reductions in central systolic and diastolic blood pressures , central pulse pressure , and left ventricular wall thickness were significant only in the nebivolol group . The change in left ventricular septal wall thickness was significantly correlated with central systolic blood pressure change ( r=0.41 ; P=0.001 ) and with central pulse pressure change ( r=0.32 ; P=0.01 ) . No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group . This proof-of-principle study provides evidence to suggest that & bgr;-blockers with vasodilating properties may offer advantages over conventional & bgr;-blockers in antihypertensive therapy ; however , this remains to be tested in a larger trial Central aortic systolic blood pressure ( BP ) is an important determinant of cardiac workload and cardiac hypertrophy . The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels . It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner . In a double-blind crossover study , we measured the effects of the four major drug classes compared with placebo on central aortic pressure . Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus . The study was undertaken in patients aged 65 to 85 years with systolic BP > 150 mm Hg at study entry . Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods .  Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme ( ACE ) inhibitors or beta-blocking drugs . On placebo , central aorta augmentation pressure and index were 23 mm Hg and 33.3 % ; on ACE inhibitors the values were 18 mm Hg and 30 % ; on beta-blockers , 26 mm Hg and 38.5 % ; on calcium channel blockers , 16 mm Hg and 28 % ; and on diuretics , 17 mm Hg and 28.8 % . The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes ( P < .05 ) , and augmentation pressures on ACE inhibitors , calcium channel blockers , and diuretics were less than on placebo ( P < .05 ) . The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics . Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs . The clinical importance of this discrepancy needs to be evaluated 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 1 . The relationship between fall in systolic blood pressure and initial systolic blood pressure has been investigated in 255 mixed normotensive and hypertensive subjects given placebo or one of five types of antihypertensive drug ( ACE inhibitors , calcium antagonists , direct vasodilators , alpha-adrenoceptor blocker , beta-adrenoceptor blocker ) .  2 . In all cases there was a significant correlation between the change in blood pressure and initial blood pressure . When Oldham 's transformation was used ( replacing the initial blood pressure by the mean of the initial and minimum pressures ) the correlation coefficients were all reduced , although five out of six were still statistically significant . 3 . In a subset of 43 hypertensive subjects given four antihypertensive agents , concentration-effect analysis was carried out . For three of the agents a linear model was used to relate effect to concentration ; for the remaining agent a Langmuir type model was used . 4 . For all four sets of data for which concentration-effect analysis was carried out , there was a significant correlation between the sensitivity of response and the initial blood pressure . 5 . The observed relationships between initial blood pressure , change in blood pressure and sensitivity of response can be qualitatively explained by postulating a general form of dose-response relationship for all antihypertensive agents Postmenopausal women are at greater risk for hypertension-related cardiovascular disease .  Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension . This r and omized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness . Overall , 125 postmenopausal hypertensive women ( age , 61.4 ± 6 years ; systolic blood pressure/diastolic blood pressure [ SBP/DBP ] , 158 ± 11/92 ± 9 mm Hg ) were r and omized  to valsartan 320 mg ± hydrochlorothiazide ( HCTZ ) ( n = 63 ) or amlodipine 10 mg ± HCTZ ( n = 62 ) . The primary outcome was carotid-to-femoral pulse wave velocity ( PWV ) changes after 38 weeks of treatment . Both treatments lowered peripheral blood pressure ( BP ) ( -22.9/-10.9 mm Hg for valsartan and -25.2/-11.7 mm Hg for amlodipine , P = not significant ) and central BP ( -15.7/-7.6 mm Hg for valsartan and -19.2/-10.3 mm Hg for amlodipine , P<.05 for central DBP ) . Both treatments similarly reduced the carotid-femoral PWV ( -1.9 vs -1.7 m/s ; P = not significant ) . Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group ( 77 % vs 14 % , P<.001 ) . BP lowering in postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement . Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering , suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects Objectives Some β-blockers are less effective in reducing central blood pressure than other antihypertensive drugs , which may explain the higher rate of events in subjects r and omized to atenolol in recent trials . We hypothesized that nebivolol , a mixed β-blocker/nitro-vasodilator , would be more effective than atenolol in reducing central blood pressure and augmentation index ( AIx ) . The aim of the present study was to test this in a double-blind , r and omized , cross-over study , in a cohort of subjects with isolated systolic hypertension . Methods Following a 2-week placebo run-in , 16 never-treated hypertensive subjects received atenolol ( 50 mg ) , nebivolol ( 5 mg ) and placebo , each for 5 weeks , in a r and om order . Seated brachial blood pressure and heart rate were measured . Aortic blood pressure , AIx and pulse wave velocity ( PWV ) were assessed non-invasively . Results The placebo-corrected fall in brachial pressure was similar between nebivolol and atenolol , as was the reduction in PWV ( mean change ± SEM : −1.0 ± 0.3 and −1.2 ± 0.2 m/s ; P = 0.2 ) . However , there was less reduction in heart rate ( −19 ± 2 versus −23 ± 2 beats/min ; P < 0.01 ) and increase in AIx ( + 6 ± 1 versus + 10 ± 1 % ; P = 0.04 ) , following nebivolol . Aortic pulse pressure was significantly lower ( 50 ± 2 versus 54 ± 2 mmHg ; P = 0.02 ) after nebivolol . N-terminal pro-B-type natriuretic peptide ( proBNP ) rose on both drugs ( 100 ± 33 versus 75 ± 80 pg/ml ; P < 0.01 for both , NS for comparison ) . Conclusions Nebivolol and atenolol have similar effects on brachial blood pressure and aortic stiffness . However , nebivolol reduces aortic pulse pressure more than atenolol , which may be related to a less pronounced rise in AIx and bradycardia . Whether this will translate into differences in clinical outcome requires further investigation When observed in elderly hypertensive patients , increased pulse pressure ( PP ) and arterial stiffness are known to be independent risk factors for cardiovascular diseases . Increased systolic blood pressure ( SBP ) leads to left ventricular hypertrophy , while decreased diastolic blood pressure ( DBP ) results in decreased coronary circulation . It is known that increased arterial stiffness is the major cause of increased PP . Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness , and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives . In this study , we compared the effects of an angiotensin-receptor blocker ( ARB : valsartan ) , an angiotensin-converting enzyme inhibitor ( ACE-I : temocapril ) , and long-acting Ca antagonists ( L- and N-type Ca channel blocker : cilnidipine ; and L-type Ca channel blocker : nifedipine CR ) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months . The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity ( baPWV ) , followed by the ACE-I and L- and N-type Ca channel blocker , while the L-type Ca channel blocker yielded no improvement . The effects on arterial stiffness and PP thus varied among the drug characteristics . Although ARB achieved the largest reduction in baPWV , this decrease was not associated with any reductions in PP , SBP , DBP , or mean blood pressure , as were the baPWV-decreases achieved by the other drugs , suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect 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 Antihypertensive agents may , even within the same class , exert variable effects on arterial stiffness variables .  Nebivolol could have a better impact than atenolol on arterial stiffness , by increasing the bioavailability of endothelium-derived nitric oxide . Angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) increase plasma renin activity ( enhancing the production of angiotensin II via non-ACE-related pathways ) whereas aliskiren does not , potentially affecting central hemodynamics differently . We compared the effects of two renin-angiotensin-aldosterone system ( RAAS ) inhibitors ( quinapril and aliskiren ) and 2 beta-blockers ( atenolol and nebivolol ) on arterial stiffness variables . Treatment-naïve patients ( n = 72 ; 68.1 % males ; age , 47.6 ± 10.6 years ) with uncomplicated stage I-II essential hypertension were r and omly assigned to quinapril , aliskiren , atenolol , or nebivolol for 10 weeks . Central systolic and diastolic blood pressure ( BP ) , central pulse pressure ( PP ) , augmentation index ( AIx ) , and pulse wave velocity ( PWV ) were measured at baseline , 2 , and 10 weeks . The same measurements were performed in 20 normotensive subjects ( 65.0 % males ; age , 40.0 ± 8.9 years ) . Peripheral and central systolic and diastolic BP , peripheral PP , and PWV were significantly and similarly reduced by all agents . However , PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol  . Central PP and AIx decreased in patients on quinapril , aliskiren , and nebivolol but did not change in those taking atenolol . The decrease in central PP and AIx did not differ between patients on quinapril , aliskiren , and nebivolol . Despite similar reductions in peripheral BP , atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics . Aliskiren exerts similar effects on markers of arterial stiffness  as quinapril . The clinical relevance of these differences remains to be established 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 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 Hypertensive African Americans often respond poorly to beta-blocker monotherapy , compared with whites . There is evidence , however , that suggests that this response may be different if beta-blockers with vasodilating effects are used . This 12-week , multi-center , double-blind , r and omized placebo-controlled study assessed the antihypertensive efficacy and safety of nebivolol , a cardioselective , vasodilating beta1-blocker , at doses of 2.5 , 5 , 10 , 20 , or 40 mg once daily in 300 African American patients with stage I or II hypertension ( mean sitting diastolic blood pressure [ SiDBP ] > or = 95 mm Hg and < or = 109 mm Hg ) . The primary efficacy end point was the baseline-adjusted change in trough mean SiDBP . After 12 weeks , nebivolol significantly reduced least squares mean SiDBP ( P < or = .004 ) at all doses of 5 mg and higher and sitting systolic blood pressure ( P < or = .044 ) at all doses 10 mg and higher , compared with placebo . The drug was safe and well-tolerated , with no significant difference in the incidence of adverse events compared with placebo . Nebivolol monotherapy provides antihypertensive efficacy , with few significant adverse effects , in hypertensive African Americans Objective : To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment  among elderly hypertensive men . Methods : The Honolulu-Asia Aging Study is a prospect i ve , community-based cohort study of Japanese American men conducted in Honolulu , Hawaii . We examined 2,197 participants ( mean age 77 years at cohort entry , 1991–1993 , followed through September 2010 ) with hypertension and without dementia or cognitive impairment at baseline , who provided information on medication use .  Cognitive function was assessed at 7 st and ardized examinations using the Cognitive Abilities Screening Instrument ( CASI ) . Cognitive impairment was defined as a CASI score < 74 . Results : A total of 854 men developed cognitive impairment  ( median follow-up , 5.8 years ) . β-Blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment ( incidence rate ratio [ IRR ] 0.69 ; 95 % confidence interval [ CI ] 0.50–0.94 ) , as compared with men not taking any antihypertensive medications , adjusting for multiple potential confounders . The use of diuretics , calcium channel blockers , angiotensin-converting enzyme inhibitors , or vasodilators alone was not significantly associated with cognitive impairment . Results were similar excluding those with cardiovascular disease or < 1 year of follow-up , and additionally adjusting for pulse pressure , heart rate , baseline and midlife systolic blood pressure , and midlife antihypertensive treatment ( IRR 0.65 ; 95 % CI 0.45–0.94 ) . The association between β-blocker use and cognitive impairment was stronger among men with diabetes , men aged > 75 years , and those with pulse pressure ≥70 mm Hg . Conclusions : β-blocker use is associated with a lower risk of developing cognitive impairment in elderly Japanese American men In the EMPA-REG BP trial , empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin , blood pressure ( BP ) , and weight versus placebo in patients with type 2 diabetes mellitus and hypertension . Patients  received placebo ( n=271 ) , empagliflozin  10 mg ( n=276 ) , or empagliflozin 25 mg ( n=276 ) for 12 weeks ( n = full analysis set ) . This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP ( SBP ) and diastolic BP ( DBP ) in patients receiving 0 , 1 , or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers . Compared with placebo , empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 ( 10 mg : −3.89/−2.58 mm Hg ; 25 mg : −3.77/−2.45 mm Hg ) , 1 ( 10 mg : −4.74/−1.97 mm Hg ; 25 mg : −4.27/−1.81 mm Hg ) , or ≥2 ( 10 mg : −2.36/−0.68 mm Hg ; 25 mg : −4.17/−1.54 mm Hg ) antihypertensives . The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP ( interaction P value 0.448 ) or DBP ( interaction P value 0.498 ) . Empagliflozin  reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use , with no significant difference between subgroups by use/no use of diuretics ( interaction P values 0.380 [ systolic ] ; 0.240 [ diastolic ] ) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers ( interaction P values 0.900 [ systolic ] ; 0.359 [ diastolic ] ) . In conclusion , in patients with type 2 diabetes mellitus and hypertension  , empagliflozin for 12 weeks reduced SBP and DBP  versus placebo , irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers . Clinical Trial Registration —URL : https:// clinical trials.gov . Unique identifier : NCT01370005 We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes , as well as its duration of action , using blood pressure ( BP ) self-monitoring at home . Seventy-six patients undergoing monotherapy with a calcium channel blocker ( CCB ) , angiotensin converting-enzyme inhibitor ( ACEI ) , or angiotensin AT1-receptor blocker ( ARB ) , but had an average morning home systolic BP ( SBP ) ≥ 135 mmHg or diastolic BP ( DBP ) ≥ 85 mmHg , were studied .  Indapamide ( 1 mg ) was added to their existing treatment once daily for 4 weeks . The additional hypotensive effects  of indapamide were evaluated by casual and home BPs , and the results were compared among the three groups of subjects classified according to their initial drug treatment classes . The morning/evening ( M/E ) ratio of BP reduction was calculated to assess the duration of the effect . Overall , indapamide significantly ( P < 0.001 ) lowered morning home BP ( 147 ± 12/87 ± 9 mmHg to 135 ± 12/81 ± 9 mmHg ) , evening home BP ( 138 ± 15/79 ± 10 mmHg to 126 ± 12/73 ± 9 mmHg ) , and casual BP ( 145 ± 21/86 ± 14 mmHg to 136 ± 17/81 ± 13 mmHg ) . All groupsshowed significant indapamide-induced home SBP/DBP decreases , whereas only the ACEI and ARB groups , but not the CCB group , showed a home pulse pressure ( PP ) reduction . Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group . The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP . Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs OBJECTIVES The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril ( Per ) and the diuretic indapamide ( Ind ) reduces central ( thoracic aorta , carotid artery ) as well as brachial systolic blood pressure ( SBP ) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP : pulse wave velocity ( PWV ) and pattern of wave reflections . BACKGROUND In high cardiovascular risk population s , angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure ( DBP ) . Whether central SBP , which is physiologically lower than brachial SBP , is significantly reduced has never been investigated . METHODS This study was a double-blind r and omized trial for one year in patients with essential hypertension . RESULTS For a similar DBP reduction , Per/Ind decreased SBP significantly more than atenolol , with a more pronounced reduction for central than for brachial SBP . After one year , the difference between brachial and central SBP was maintained by Per/Ind ( 8.28 + /- 1.53 mm Hg ) and significantly attenuated by atenolol ( 0.29 + /- 1.61 mm Hg ) . Under atenolol , the principal factor modulating SBP reduction was mean blood pressure . Under Per/Ind , this parameter played a minor role , and the central SBP reduction implied a major role for disturbed PWV and wave reflections . CONCLUSIONS Under Per/Ind , but not atenolol , normalization of brachial SBP is achieved with a significantly greater reduction of central SBP . This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory , where Per/Ind , but not atenolol , is known to improve vessel wall structure BACKGROUND Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics , beta-blockers , angiotensin-converting enzyme inhibitors , central alpha-agonists , and other vasodilators . Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal . METHODS A three-phase , r and omized , double-blind , placebo-controlled  multicenter study included 162 patients aged 18 to 75 years with essential hypertension . After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride , patients received ibuprofen , naproxen , or placebo matching capsules for 3 weeks , and blood pressure , heart rate , weight , and adverse effects were evaluated . A general linear model with 95 % confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group . RESULTS No significant differences in sitting , st and ing , or supine blood pressure were noted with naproxen or ibuprofen compared with placebo . The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar . Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies . Changes in pulse rate were not significant . The incidence of adverse effects was similar across all three treatment groups . CONCLUSIONS The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure .  Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy Objective Hypertension guidelines recommend initial treatment with a β-blocker or diuretic and adding the other drug where blood pressure is not controlled . We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient 's response , and suggest a more rational approach to choosing best treatment . Design Thirty-four young hypertensives ( age 28–55 , median 47 ) rotated in a double-blind , Latin-square , crossover fashion through 6 weeks of treatment each with amlodipine , doxazosin , lisinopril , bisoprolol , bendrofluazide and placebo . Blood pressure was measured at each visit . ‘ Best ’ drug , defined by efficacy and tolerability , was repeated at the end . Results Rotation doubled the number of patients reaching target blood pressure ( systolic < 140 mmHg ) on one drug ( P = 0.03 ) . All five drugs were represented among the ‘ best ’ drugs . In six patients , the blood pressure on ‘ best ’ drug was at least 10 mmHg lower than on any other . Response to the ‘ best ’ drug was highly correlated ( r = 0.79 ) with its previous administration . By contrast , there were only weak correlations between responses to pairs of drugs , except for angiotensin-converting enzyme ( ACE ) inhibitor ( A ) with β-blocker ( B ) , and calcium blocker ( C ) with diuretic ( D ) – each r = 0.71 , P < 0.005 ) . In these young patients , the majority of patients ( 23/34 ) responded best to a drug suppressing the renin system ( A and B ) . Conclusions Patients vary reproducibly in their response to initial treatment , and switching among drugs can increase the efficacy of monotherapy . The results support an AB/CD scheme for choosing therapy , in which the first drug is taken from one of these pairs , and uncontrolled patients switch to one of the other pair 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 The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by  24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP < 90 and < 85 mmHg . Control rates for SBP < 140 and < 130 mmHg were also calculated . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of < 130 mmHg and the DBP goal of < 85 mmHg . Both drugs were well tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg Persistence on treatment affects the efficacy of antihypertensive treatment . We prospect ively investigated the persistence on therapy and the extent of  blood pressure ( BP ) control  in 347 hypertensive patients ( age 59.4 ± 6 years ) r and omly allocated to a first-line treatment with : angiotensin-converting enzyme ( ACE ) inhibitors , calcium-channel blockers ( CCBs ) , ß-blockers , angiotensin-II receptor blockers ( ARBs ) , or diuretics and followed-up for 24-months . Persistence on treatment was higher in patients treated with ARBs ( 68.5 % ) and ACE inhibitors ( 64.5 % ) vs CCBs ( 51.6 % ; p < 0.05 ) , β-blockers ( 44.8 % , p < 0.05 ) , and diuretics ( 34.4 % , p < 0.01 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class . The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs ( 59.3 % vs 46.6 % , p < 0.05 ) . Systolic and diastolic BP was decreased more successfully in patients treated with ARBs ( −11.2/−5.8 mmHg ) , ACE inhibitors ( −10.5/−5.1 mmHg ) , and CCBs ( −8.5/−4.6 mmHg ) compared with ß-blockers ( −4.0/−2.3 mmHg p < 0.05 ) and diuretics ( −2.3/−2.1 mmHg , p < 0.05 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class . A trend toward a better BP control was observed in response to lercanidipine vs other CCBs ( p = 0.059 ) . The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice BACKGROUND Blood pressure ( BP ) is controlled by a variety of systems , the activities of which vary throughout the day . As drugs are developed that selectively block these systems , the fall in BP may not be consistent over 24 h. METHODS A total of 24 patients ( aged > 65 years ) with systolic BP ( SBP ; > 150 mm Hg ) that had not been treated entered a sub study of a larger study performed in 74 patients . In a double blind , crossover study with a balanced design , they received placebo , atenolol 50 mg , perindopril 8 mg , felodipine 10 mg , or hydrochlorothiazide 50 mg . The study periods were 2 months . Ambulatory BP monitoring was performed at the end of each period , and was divided into awake periods ( 9:00 AM to 10:00 PM ) , sleep periods ( 12:00 AM to 6:00 AM ) , and morning periods ( 6:00 AM to 9:00 AM ) . Medication was taken at 9:00 AM . RESULTS The four drug classes lowered 24-h mean SBP ( P < .05 ) , but the fall with atenolol was less than with the other drugs . The fall in awake BP with perindopril was less than with felodipine or hydrochlorothiazide . Atenolol caused no significant fall in sleep or morning SBP , and the falls with the other three drugs were significant and were greater than the fall with atenolol . The fall in sleep BP with perindopril was greater than with the other drug classes . The awake-sleep difference in SBP increased with perindopril , stayed the same with felodipine and hydrochlorothiazide , and was reduced by atenolol . CONCLUSIONS In this study , the response to the different drug classes differed . The response to drugs that work relatively nonspecifically ( diuretics , calcium blockers ) was relatively consistent over 24 h. The response to beta blockers and to angiotensin converting enzyme inhibitors reflected the activity of control systems . This finding supports the concept of multiple drug therapy that may need to be tailored to the time of day BACKGROUND Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension . METHODS In 569 patients with mild-to-moderate hypertension , blood pressure ( BP ) , plasma renin activity ( PRA ) and plasma renin concentration ( PRC ) were measured before and after 8 weeks of double-blind treatment with once-daily oral doses of aliskiren ( 150 , 300 or 600 mg ) , irbesartan 150 mg or placebo . RESULTS Aliskiren 150 , 300 and 600 mg and irbesartan 150 mg significantly reduced mean cuff sitting systolic BP ( SBP ) from baseline ( p < 0.001 vs. placebo ) . Aliskiren 150 , 300 and 600 mg significantly reduced geometric mean PRA by 69 % , 71 % and 75 % from baseline respectively ( p < 0.05 vs. placebo ) . Irbesartan 150 mg significantly increased PRA by 109 % ( p < 0.05 vs. placebo ) . Aliskiren dose-dependently increased PRC from baseline by 157 % , 246 % and 497 % , at 150 , 300 and 600 mg respectively , compared with a 9 % decrease with placebo ( p < 0.05 ) . PRC increased significantly more with aliskiren 300 and 600 mg compared with irbesartan 150 mg ( 105 % ; p < 0.05 ) . Regression analysis showed no significant correlations between baseline PRA and changes in SBP in any of the treatment groups , but interestingly , the slopes of the regression lines between changes in SBP and log-transformed baseline PRA were + 2.0 for placebo and -1.5 , -1.8 and -2.3 for aliskiren 150 , 300 and 600 mg respectively . The slope for irbesartan 150 mg ( -1.4 ) was similar to that for aliskiren 150 mg . CONCLUSIONS Aliskiren reduces SBP and PRA and increases PRC dose-dependently . In contrast , irbesartan reduces SBP but increases both PRC and PRA . As PRA is a measurement of angiotensin I-generating capacity , PRA can be used for measuring the ability of an antihypertensive agent to prevent the generation or action of Ang II , either directly ( renin inhibitors , beta-blockers , central alpha(2)-agonists ) or indirectly ( AT(1)-receptor blockers , ACE inhibitors ) A large-scale , 8-week , open-label , clinical experience trial evaluated the efficacy of the angiotensin II receptor ( AT1 subtype ) blocker c and esartan cilexetil ( 16 to 32 mg once daily ) either alone or as add-on therapy in 6465 hypertensive patients . The study population was 52 % female and 16 % African American with a mean age of 58 years . It included 5,446 patients who had essential hypertension ( HBP ) and 1,014 patients who had isolated systolic hypertension ( ISH ) . These patients had either untreated or uncontrolled hypertension ( systolic blood pressure [ SBP ] 140 to 179 mm Hg or diastolic blood pressure [ DBP ] 90 to 109 mm Hg inclusive at baseline ) despite a variety of antihypertensive medications including diuretics , calcium antagonists , angiotensin converting enzyme ( ACE ) inhibitors , and alpha- or beta-blockers , either singly or in combination . The mean baseline blood pressure for the HBP group was 156/97 mm Hg . C and esartan cilexetil as monotherapy ( in 51 % of HBP patients ) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg . As add-on therapy ( in 49 % of HBP patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.8/11.3 mm Hg ) , calcium antagonists ( 16.6/11.2 mm Hg ) , beta-blockers ( 16.5/ 10.4 mm Hg ) , ACE inhibitors ( 15.3/10.0 mm Hg ) , alpha-blockers ( 16.4/10.4 mm Hg ) . The mean baseline blood pressure for the ISH group was 158/81 mm Hg . C and esartan cilexetil , as monotherapy ( in 34 % of ISH patients ) , reduced SBP/DBP by 17.0/4.4 mm Hg . As add-on therapy ( in 66 % of ISH patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.4/5.1 mm Hg ) , calcium antagonists ( 15.6/3.6 mm Hg ) , beta-blockers ( 14.0/4.8 mm Hg ) , ACE inhibitors ( 13.4/4.3 mm Hg ) , and alpha-blockers ( 11.6/4.5 mm Hg ) . The further blood pressure lowering effects of c and esartan cilexetil as add-on therapy were seen regardless of age , sex , and race . Overall , 6.8 % of the 6465 patients withdrew because of adverse events , most commonly headache ( 6.3 % ) and dizziness ( 5.0 % ) . Orthostatic hypotension was infrequent ; 0.2 % with c and esartan cilexetil alone , and 0.8 % with c and esartan cilexetil as add-on therapy . Thus , c and esartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice setting BACKGROUND Analyses of some r and omised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that beta blockers are less effective than expected . We aim ed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk . METHODS The Anglo-Sc and inavian Cardiac Outcomes Trial Blood Pressure Lowering Arm ( ASCOT-BPLA ) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council ( MRC ) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65 - 74 years . We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as st and ard deviation ( SD ) and as transformations uncorrelated with mean blood pressure . For ASCOT-BPLA , we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring ( ABPM ) . RESULTS In ASCOT-BPLA , group systolic blood pressure ( SBP ) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits ( p<0.0001 ) , mainly because of lower within-individual visit-to-visit variability . Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group ( all p<0.0001 ) . Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group . The lower risk of stroke in the amlodipine group ( hazard ratio 0.78 , 95 % CI 0.67 - 0.90 ) was partly attenuated by adjusting for mean SBP during follow-up ( 0.84 , 0.72 - 0.98 ) , but was abolished by also adjusting for within-individual SD of clinic SBP ( 0.99 , 0.85 - 1.16 ) . Findings were similar for coronary events . In the ABPM sub study , reduced variability in daytime SBP in the amlodipine group ( p<0.0001 ) partly accounted for the reduced risk of vascular events , but reduced visit-to-visit variability in clinic SBP had a greater effect . In the MRC trial , group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up ( all p<0.0001 ) . Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk . INTERPRETATION The opposite effects of calcium-channel blockers and beta blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure . To prevent stroke most effectively , blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability ; ideally they should reduce both Renin – angiotensin system ( RAS ) blockers have shown clinical outcomes superior to those of the beta (β)-blocker atenolol , despite similar reductions in the peripheral blood pressure ( BP ) , perhaps because of different impacts on central hemodynamics . However , few comparative studies of RAS blockers and newer vasodilating β-blockers have been performed . We compared the central hemodynamic effects of losartan and carvedilol in a prospect i ve , r and omized , open , blinded end point study . Of the 201 hypertensive patients enrolled , 182 ( 49.6±9.9 years , losartan group=88 and carvedilol group=94 ) were analyzed . Carotid-femoral pulse wave velocity ( cfPWV ) , aortic augmentation index ( AIx ) , AIx corrected for a heart rate ( HR ) of 75 beats per minute ( AIx@HR75 ) and central BP were measured noninvasively at baseline and after a 24-week treatment regimen with losartan or carvedilol . After 24 weeks , there were no between-group differences in the brachial BP , cfPWV , AIx@HR75 or central BP changes , except for a more favorable AIx effect with losartan . The changes in all measured metabolic and inflammatory parameters were also not significantly different between the two groups , except for uric acid . Losartan and carvedilol showed generally comparable effects on central hemodynamic indices , metabolic profile , inflammatory parameters and peripheral arterial pressure with a 24-week treatment Hypertensive patients may be adversely affected by complications and other concomitant processes such as anxiety , sedation , and drug side effects . It has been suggested that some recently developed antihypertensive agents do not affect quality of life by causing adverse effects . We compared the effects of two antihypertensive drugs on quality of life : atenolol , a st and ard cardioselective β-blocker , and celiprolol , one of a new class of selective β-blockers with vasodilatory properties . One hundred thirty-two patients with mild-to-moderate hypertension were eligible to enter a 28-week , double-blind , parallel-group study . The study protocol consisted of a 4-week period on placebo and a 24-week period of dosage-adjusted treatment with either atenolol or celiprolol . We assessed both systolic and diastolic blood pressure and quality of life perception by a selected test battery that included the Bulpitt and Fletcher Quality of Life Question naire . Supine blood pressure fell from 167/101 ( range 120/95 to 200/116 ) to 150/92 mm Hg ( p < 0.0001 ) during celiprolol treatment . This antihypertensive effect was at least as good with celiprolol as with atenolol  . Quality of life perception was comparable for the two drugs although adverse effects were seen more frequently with atenolol than with celiprolol , particularly after prolonged treatment . Patient compliance was better for celiprolol than for atenolol . Our results show that the selective β-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it is more advantageous in terms of some quality of life variables Nonsteroidal antiinflammatory drugs ( NSAIDs ) are known to attenuate the antihypertensive effects of a variety of antihypertensive agents including diuretics , beta-blockers , and vasodilators . Because of their unique mechanisms of actions , calcium channel blockers may not be subject to this interaction . This multicenter , double-blind , r and omized , placebo-controlled study was design ed to assess the effect of NSAID therapy on blood pressure control in stable hypertensive patients treated with a calcium channel blocker . One hundred patients with stable blood pressure control on 30 mg nicardipine three times a day were treated with 375 mg naproxen twice a day or placebo for 4 weeks . The mean diastolic blood pressures and estimated mean arterial pressures in both groups changed < 1 mm Hg during the 4 weeks of study drug treatment . None of the changes was significantly different from baseline and the two treatment groups were not significantly different from each other . Body weight in the placebo-treated patients did not change significantly whereas body weight in the naproxen-treated patients increased significantly , from 90.3 + /- 3.2 kg to 91.0 + /- 3.2 kg ( mean = 0.7 , P = .0003 ) . At 4 weeks there was a mean loss of 0.1 kg in the placebo group and a mean gain of 0.4 kg in the naproxen group compared to baseline weights , neither of which was statistically significant ( P = .60 and P = .071 , respectively ) . These results indicate that despite a significant increase in body weight , the antihypertensive action of the calcium channel blocker nicardipine is not significantly affected by cotreatment with naproxen BACKGROUND A high pulse pressure is an independent cardiovascular risk factor . It has therefore been suggested that antihypertensive treatment should not only reduce systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) , but should also decrease pulse pressure ( SBP minus DBP ) . In a previous analysis , we showed that two angiotensin II type 1 (AT1)-receptor blockers , c and esartan cilexetil and losartan , differed in their effects in reducing SBP and DBP . OBJECTIVE To compare the efficacy of c and esartan cilexetil and losartan according to a new approach -- their effect on pulse pressure-- and to describe the dose-effect relationship for SBP , DBP and pulse pressure , in a placebo-controlled study . METHODS After a 4-week placebo run-in period , 268 patients with mild-to-moderate hypertension were allocated r and omly to groups to receive placebo , c and esartan cilexetil ( 8 mg once daily ) or losartan ( 50 mg once daily ) , for 4 weeks . The doses were then doubled to 16 and 100 mg , respectively , for the final 4 weeks of the study . Clinic blood pressure was measured 24 and 48 h after each dose of drug or placebo , and ambulatory blood pressure was monitored from 0 to 36 h after each dose , at baseline and after 4 and 8 weeks of treatment . RESULTS C and esartan cilexetil decreased ambulatory pulse pressure significantly ( P < 0.05 ) more than did losartan during both daytime and night-time , and over the 24 h period after the previous dose . A different dose-effect relationship on SBP , DBP and pulse pressure was observed . The duration of action of c and esartan cilexetil was greater than that of losartan . After a missed dose ( i.e. approximately 24 - 36 h after the previous dose ) , mean ambulatory pulse pressure values after 4 and 8 weeks of treatment with c and esartan cilexetil were lower than those observed with losartan ( P < 0.005 ) . Clinic pulse pressure measurements were consistent with these ambulatory measurements . CONCLUSIONS AT1 -receptor blockers differ both in their ability to reduce pulse pressure and in their duration of effect , c and esartan cilexetil having a greater and more sustained effect than losartan . Different dose-effect relationships on SBP , DBP or pulse pressure were observed . Further prospect i ve studies based on pulse pressure are needed to analyse the mechanism of reduction of pulse pressure and to determine its prognostic value Identifying dietary modifications that potentiate the blood pressure (BP)-lowering effects of antihypertensive medications and that are practical for free-living people may assist in achieving BP reduction goals . We assessed whether two dietary patterns were effective in lowering BP in persons on antihypertensive therapy and in those not on therapy . Ninety-four participants ( 38/56 females/males ) , aged 55·6 ( SD 9·9 ) years , consumed two 4-week dietary regimens in r and om order ( Dietary Approaches to Stop Hypertension (DASH)-type diet and low- Na high-K ( LNAHK ) diet ) with a control diet before each phase . Seated home BP was measured daily for the last 2 weeks in each phase . Participants were grouped based on antihypertensive drug therapy . The LNAHK diet produced a greater fall in systolic BP ( SBP ) in those on antihypertensive therapy ( -6·2 ( SD 6·0 ) mmHg ) than in those not on antihypertensive therapy ( -2·8 ( SD 4·0 ) mmHg ) ( P = 0·036 ) , and this was greatest for those on renin-angiotensin system ( RAS ) blocker therapy ( -9·5 ( SD 6·4 ) mmHg ) ( interaction P = 0·007 ) . The fall in SBP on the DASH-type diet , in those on therapy ( overall -1·1 ( SD 6·2 ) mmHg ; renin-angiotensin blocker therapy -4·2 ( SD 4·7 ) mmHg ) , was not as marked as that observed on the LNAHK diet . Dietary modifications are an important part of all hypertension management regimens , and a low-Na and high-K diet enhances the BP-lowering effect of antihypertensive medications , particularly those targeting the RAS There is little information about the hemodynamic and exercise-response implication s of renin-angiotensin system blocker combinations . After a 3-week lisinopril ( L ; 40 mg/day ) run-in , carvedilol ( C ; 20 then 40 mg/day ) or valsartan ( V ; 160 then 320 mg/day ) was added to L for 4 weeks each in a forced-titration , r and om order-entry crossover study in 30 subjects .  Arterial tonometry ( central pressures and time-tension index , TTI ) ; impedance cardiography ( steady-state hemodynamics ) , and ultrasound ( carotid flow )  were performed at rest and during supine bicycle exercise at 30 and 60 watts . At rest , both V and C lowered TTI similarly ( 7 % to 9 % , P = .05 compared with L , in part because they lowered blood pressure ( 3 to 7/3 to 4 mm Hg ) . V lowered central systolic pressure , augmentation pressure ( AP ) , and systemic vascular resistance ( SVR , all P < .02 ) ; C lowered heart rate but not central systolic pressure or SVR . During exercise , V persistently lowered central systolic pressure , AP , and SVR , whereas C did not . Neither drug affected exercise responses or carotid blood flow . Adding V or C to an angiotensin-converting enzyme inhibitor reduced cardiac workload by different mechanisms : vasodilation and reduced central blood pressure with V and lower heart rate with Hypertension is a major risk factor for cardiovascular and cerebrovascular events , and most patients with hypertension are administered antihypertensive drugs . However , not all patients achieve normal blood pressure levels . The new angiotensin receptor blocker azilsartan ( Takeda Pharmaceutical Company Limited , Osaka , Japan ) has been reported to have a strong hypotensive effect . Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers . This study included 17 hypertensive patients on HD , who had been administered angiotensin receptor blockers , except for azilsartan , for more than 6 months before enrolling , and after enrollment , they were switched to azilsartan .  Blood tests , Holter electrocardiogram , ambulatory blood pressure monitoring , and echocardiography  were performed at baseline and at the 6-month follow-up . The blood pressure from baseline to 6 months had significantly decreased ( 24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg , P = 0.008 ) , awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg , P = 0.01 , sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg , P = 0.005 ) . There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan ( from 550.1 ± 282.9 pg/mL , to 351.7 ± 152.3 pg/mL , P = 0.002 ; from 117.0 ± 26.4 g/m(2 ) to 111.3 ± 23.9 g/m(2 ) , P = 0.01 , respectively ) . Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers . Thus , the switch to azilsartan might improve prognosis of hemodialysis patients . We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system We studied the structural and functional characteristics of the vascular bed at calf level in 46 middle aged hypertensive patients ( 20 males and 26 females ) treated with different beta-blockers . After one week of placebo , the patients were divided into three groups : group 1 was treated with labetalol , an alpha-beta-blocker ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 3 was treated with metoprolol , a cardioselective beta-blocker without ISA ( 100 mg t.t.d . ) . Before and after placebo , and after three months of active drug treatment , we measured blood pressure , and rest and peak flow at the calf level by strain gauge plethysmography . Basal and minimal vascular resistances were calculated as the ratio between mean blood pressure and rest or peak flow , respectively . A significant decrease in blood pressure was observed in each group . However , basal and minimal vascular resistances decreased only in the labetalol-treated group . These observations indicate that antihypertensive agents that have similar effects on blood pressure , may have different effects on minimal vascular resistance . Therefore , maximum vasodilation of arterioles improves , suggesting that long term treatment with labetalol , but not with other beta-blockers is able to induce a partial regression of vascular structural alterations in hypertensive patients Objective . Angiotensin-converting enzyme ( ACE ) inhibitors have been shown to lower central augmentation index ( cAI ) , an index of arterial wave reflection , more than β-blockers . We tested whether this is also true for long-term treatment with an angiotensin receptor blocker ( ARB ) . Methods . One-hundred and fifty-six subjects with essential hypertension were r and omised to treatment with either irbesartan or atenolol .  cAI and central blood pressure ( BP ) were determined by pulse wave analysis from the radial and the carotid artery after six and after 18 months treatment . Results . Peripheral and central systolic and diastolic BP were reduced to a similar extent A in the two groups . cAI was reduced with irbesartan , but increased with atenolol ( derived from the carotid artery : -6±10 vs. -4±12 % after six months , p<0.001 ; —4±12 vs. + 1±11 % after 18 months ; p=0.011 ) . Furthermore , central to peripheral pulse pressure ( PP ) amplification was unaffected by treatment with irbesartan , but decreased with atenolol . Conclusions . Although treatment with irbesartan and atenolol  similarly decreased peripheral and central BP , only treatment with irbesartan had beneficial effects on arterial wave reflection and preserved PP amplification . These haemodynamic effects may at least partly explain the reported differential effects of ARB versus β-blocker treatment on cardiovascular mortality in patients with essential hypertension Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future Summary : A r and omized , double‐blind , placebo‐controlled study was set up to study the effects of acute and chronic administration of  carvedilol  , a vasodilatory & bgr;‐blocker in essential hypertension . Acute administration of a single dose of 50 mg of carvedilol reduced systolic and diastolic blood pressure , without inducing reflex tachycardia . Renal blood flow was preserved : accordingly renal vascular resistance was significantly reduced . A significant reduction of glomerular filtration rate and filtration fraction was observed . Plasma renin activity ( PRA ) and plasma aldosterone were not changed . Chronic carvedilol treatment produced a significant fall in systolic and diastolic office and ambulatory blood pressure , heart rate , cardiac output , PRA and plasma aldosterone . Blood pressure variability was not changed . Renal blood flow , glomerular filtration rate and filtration fraction also remained unchanged ; renal vascular resistance decreased significantly . It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties , both acutely and after chronic treatment
In conclusion , NVBBs , but not VBBs , determine a lower reduction in cSBP than in pSBP .
However , the difference in treatment-induced SBP amplification changes between NVBB and VBB is nearly abolished after accounting for differences in heart rate changes
β-Blockers are less effective than other antihypertensive drug classes in reducing central systolic blood pressure ( cSBP ) as compared with peripheral SBP ( pSBP ) .
Whether this effect is less pronounced with vasodilating β-blockers ( VBB ) when compared with nonvasodilating β-blockers ( NVBB ) remains unsettled .