ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives Effect of different antihypertensive drug classes on central aortic pressure. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study South African hypertension guideline 2011. Beta-blockers versus saluretics in hypertension. Comparison of total mortality, myocardial infarction, and sudden death: study design and early results on blood pressure reduction. Adjusted Drug Treatment Is Superior to Renal Sympathetic Denervation in Patients With True Treatment-Resistant Hypertension Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial. Influence of diabetes and type of hypertension on response to antihypertensive treatment. Ambulatory Blood Pressure and Left Ventricular Changes During Antihypertensive Treatment: Perindopril Versus Isradipine Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group. Crossover design to test antihypertensive drugs with self-recorded blood pressure. Differential effects of beta-adrenoreceptor antagonists on central and peripheral blood pressure at rest and during exercise. The role of diastolic blood pressure when treating isolated systolic hypertension.
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 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 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 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 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 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 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 Abstract Beta-blocking drugs may be more effective than saluretic diuretics in reducing the total mortality and incidence of myocardial infa rct ion , sudden death and stroke in middle-aged men with mild to moderate hypertension . To test this hypothesis , an international multicenter , r and omized study is in progress , and its design and some early results are presented here . It is probable that 4,000–5,000 men will need to be enrolled for five years to show a statistically significant difference between treatments . Identical control of blood pressure in the two treatment groups is m and atory , and has been achieved using a fixed therapeutic schedule . The ongoing study will be completed during 1985–1990 & NA ; We aim ed to investigate for the first time the blood pressure (BP)–lowering effect of renal sympathetic denervation ( RDN ) versus clinical ly adjusted drug treatment in true treatment-resistant hypertension ( TRH ) after excluding patients with confounding poor drug adherence . Patients with apparent TRH ( n=65 ) were referred for RDN , and those with secondary and spurious hypertension ( n=26 ) were excluded . TRH was defined as office systolic BP ( SBP ) > 140 mm Hg , despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic . In addition , ambulatory daytime SBP > 135 mm Hg after witnessed intake of antihypertensive drugs was required , after which 20 patients had normalized BP and were excluded . Patients with true TRH were r and omized and underwent RDN ( n=9 ) performed with Symplicity Catheter System versus clinical ly adjusted drug treatment ( n=10 ) . The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect . Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg ( ±SD ) at baseline to 132±10/77±8 mm Hg at 6 months ( P<0.0005 and P=0.02 , SBP and diastolic BP , respectively ) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg ( P=0.42 and P=0.48 , SBP and diastolic BP , respectively ) . SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months ( P=0.002 and P=0.004 , respectively ) , and absolute changes in SBP were larger in the drug-adjusted group ( P=0.008 ) . Ambulatory BPs changed in parallel to office BPs . Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : Dihydropyridine and nondihydropyridine calcium channel blockers ( CCB ) differ in pharmacologic characteristics . Few clinical studies distinguish effects of CCB as monotherapy . We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension . Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were r and omly assigned to either nifedipine-GITS or verapamil-SR . Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks . Clinic blood pressure ( BP ) , 24-h ambulatory BP , exercise BP , left ventricular mass , systolic and diastolic function by echocardiography , and coronary flow reserve by split-dose thallium-201 imaging  with adenosine were assessed at baseline , end of titration , 3 months and 6 months of treatment . Plasma renin activity , atrial natriuretic peptide , norepinephrine , and epinephrine were assayed . Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index . Compared to nifedipine-GITS , verapamil-SR produced a significantly lower resting and peak exercise heart rate .  Nifedipine-GITS elicited a lower peak exercise systolic BP . At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels , no longer apparent by 6 months . Plasma norepinephrine was lower with verapamil-SR , also at end titration and at 3 months , but not at 6 months . Plasma epinephrine and plasma renin activity were unchanged by either drug . There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments . Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension . Differences in their hemodynamic profiles and neurohormonal responses are consistent with pre clinical pharmacologic characteristics . The clinical implication s of their similarities and differences remain to be fully evaluated in outcome studies Antihypertensive medications are used extensively in children despite a paucity of r and omized , placebo-controlled trials . This study was among the first r and omized , controlled pediatric antihypertensive medication trials , in which the combination drug bisoprolol fumarate/hydrochlorothiazide ( B/HT ) was compared with placebo . The study comprised a 2-week single-blind placebo screening period , a 6-week double-blind dose titration period , a 4-week double-blind dose maintenance period , and a 2-week double-blind dose-tapering period . One hundred and forty subjects were enrolled to achieve 94 r and omized subjects treated either with B/HT ( n=62 ) or placebo ( n=32 ) . B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure ( SiSBP ) ( 9.3 vs. 4.9 mmHg , P<0.05 ) and sitting diastolic blood pressure ( SiDBP ) ( 7.2 vs. 2.7 mmHg , P<0.05 ) . The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension . The percentage of subjects with BP less than the 90th percentile at study completion was 45 % for B/HT and 34 % for placebo ( P = NS ) . Although the study demonstrated that B/HT  reduced BP safely compared with placebo , the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension , particularly in adolescents with mild-to-moderate BP elevation The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension ( diastolic or isolated systolic ) influences blood pressure ( BP ) response to treatment . The International Nifedipine GITS Study : Intervention as a Goal in Hypertension Treatment ( INSIGHT ) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years . Dynamic r and omization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors . Patients with isolated systolic hypertension were also separately r and omized . Atenolol or enalapril was the m and atory second-line drug . In 5669 patients who completed the 18-week titration , BP fell from 172+/-15/99+/-9 mm Hg ( mean+/-SD ) while receiving placebo to 139+/-12/82+/-7 mm Hg . Twenty-six percent of patients required 2 drugs , and 4 % required 3 drugs . Patients with diabetes were the most resistant to treatment , requiring second and third drugs 40 % and 100 % more frequently than patients without diabetes and achieving marginally the highest final BP , for any risk group , of 141+/-13/82+/-8 mm Hg . Age , smoking , gender , hypercholesterolemia , left ventricular hypertrophy , and existing atherosclerosis had little ( < 1 mm Hg ) or no influence on BP at the end of titration , but all except smoking slightly reduced the initial response of either systolic or diastolic BP . Patients with isolated systolic hypertension were slightly more responsive than average to treatment . Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension , the risk factors themselves do not prevent the recommended BP targets from being achieved Using digitized M-mode echocardiograms and 24-h ambulatory blood pressure ( BP ) monitoring , we compared the effects on left ventricle ( LV ) and BP of 6-month treatment with a calcium antagonist or an angiotensin-converting enzyme ( ACE ) inhibitor in 36 hypertensive patients with LV hypertrophy ( group 1 , 18 subjects treated with sustained-release isradipine ; group 2 , 18 subjects treated with perindopril ) . At the basal evaluation , the two groups had comparable BP and LV parameters . After treatment , both groups showed a similar and significant reduction in 24-h , day- and night-systolic and diastolic BP ( SBP , DBP ) . The reduction in LV mass index was greater ( p < 0.01 ) in group 2 . In group 1 , percentage of decrease of LV mass correlated significantly with percentage of decrease in 24-h and daytime BP ; this was not true of group 2 . Together with the reduction in LV hypertrophy , there was a significant increase of peak lengthening rate of LV diameter that was greater ( p < 0.01 ) in group 1 . Both drugs can reduce LV hypertrophy and improve diastolic function . The reduction of hypertrophy induced by perindopril appears to be partly independent of BP decrease and therefore partly related to a direct action of perindopril on the myocardium Myocardial infa rct ion , sudden cardiac death , cerebrovascular accidents , blood pressure control and treatment tolerability were studied in a r and omized double-blind trial conducted in 6357 men and women aged 40 - 64 years with uncomplicated essential hypertension ( diastolic blood pressures 100 - 125 mmHg ) . At the start of the trial 3185 patients received treatment based on a beta-blocker ( oxprenolol )  , while in the remaining 3172 placebo replaced oxprenolol .  Supplementary drugs , excluding beta-blockers , were used as necessary in both treatment groups , with the aim of reducing diastolic pressure to 95 mmHg or less . Patients were followed for 3 - 5 years , a total of 25 651 patient years at risk . In most respects the two groups fared equally well ; sudden death ( relative risk [ RR ] 1.08 ; 95 % confidence interval [ Cl ] 0.68 and 1.72 ) , myocardial infa rct ion ( RR 0.83 ; Cl 0.59 and 1.16 ) and cerebrovascular accident ( RR 0.97 ; Cl 0.64 and 1.47 ) rates were similar . Beta-blocker based therapy was associated with significantly lower average blood pressures , earlier ECG normalization , less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension . Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability . In smokers the cardiac event rate was doubled . We propose that beta-blocker treatment effects depend on smoking status , with a significant interaction benefiting non-smoking men . Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events . Proportional hazards analysis also underlines the importance of other cardiovascular risk factors . The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients In a double-blind , within-patient study , blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient . Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone ( 25 mg ) and triamterene ( 50 mg ) and the beta-blocker oxprenolol ( 160 mg ) and the greater efficacy of the combination of the two therapies . During placebo , as well as during active treatment , blood pressure values were higher at the clinic than at home , except when the patients were taking the beta-blocker , which minimized the arousal response during blood pressure measurements in the clinic . With 2-week treatment periods , separated by 2 weeks of placebo administration , blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5 % level . This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home , at the usual statistical risks ( alpha = 5 % , beta = 10 % ) , a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo . Moreover , at the end of this 3-month follow-up , each patient could continue to receive the treatment that was the most effective and the best tolerated . In conclusion , the use of a within-patient trial design , with a 15-day washout period between active treatments and careful recording of blood pressure values , can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment BACKGROUND Differential effects of beta-adrenoreceptor antagonists ( beta-ARB ) on central and peripheral blood pressure may relate to change in heart rate and /or vasodilator tone and thus be exaggerated during exercise . AIMS To examine acute effects of selective and nonselective beta-ARB on central and peripheral blood pressure , cardiac output and peripheral vascular resistance during exercise . METHODS Healthy volunteers ( n= 20 , 18 men , 19 - 54 years ) received propranolol 80 mg , bisoprolol 20 mg , and placebo 1 h before bicycle ergometry ( 50 , 75 and 100 W each for 3 min ) in a r and omized , cross-over study . Cardiac output was determined by pulmonary uptake of soluble and inert gas tracers ( InnoCor , Innovision ) . Central systolic blood pressure ( SBP ) was determined from the late systolic shoulder of the digital artery pressure waveform ( Finometer , Finopres ) . RESULTS At rest , both beta-ARB reduced brachial but not central SBP ( compared with placebo ) . During exercise , beta-ARB reduced brachial SBP ( reductions of 19.9 + /- 4.3 mmHg and 23.2 + /- 2.7 mmHg for propranolol and bisoprolol , respectively , at 100 W , each P < 0.0001 ) but not central SBP . The difference between peripheral and central SBP was reduced , relative to that during placebo , by 21.5 mmHg ( 95 % confidence interval 8.8 , 34.1 ) and 26.4 mmHg ( 18.1 , 34.8 ) for propranolol and bisoprolol , respectively , at 100 W ( each P < 0.01 ) . There was no significant effect of beta-ARB on diastolic blood pressure or peripheral vascular resistance . CONCLUSIONS Despite reducing brachial blood pressure , acute beta-adrenoreceptor blockade in man at rest and during exercise does not reduce central blood pressure OBJECTIVE To assess the role of treated diastolic blood pressure ( DBP ) level in stroke , coronary heart disease ( CHD ) , and cardiovascular disease ( CVD ) in patients with isolated systolic hypertension ( ISH ) . DESIGN An analysis of the 4736 participants in the Systolic Hypertension in the Elderly Program ( SHEP ) was undertaken . The SHEP was a r and omized multicenter double-blind outpatient clinical trial of the impact of treating ISH in men and women aged 60 years and older . MAIN OUTCOME MEASURES Cox proportional hazards regression analysis , with DBP and systolic blood pressure ( SBP ) as time-dependent covariables . RESULTS After adjustment for the baseline risk factors of race ( black vs other ) , sex , use of antihypertensive medication before the study , a composite variable ( diabetes , previous heart attack , or stroke ) , age , and smoking history ( ever vs never ) and adjustment for the SBP as a time-dependent variable , we found , for the active treatment group only , that a decrease of 5 mm Hg in DBP increased the risk for stroke ( relative risk , [ RR ] , 1.14 ; 95 % confidence interval [ CI ] , 1.05 - 1.22 ) , for CHD ( RR , 1.08 ; 95 % CI , 1.00 - 1.16 ) , and for CVD ( RR , 1.11 ; 95 % CI , 1.05 - 1.16 ) . CONCLUSIONS Some patients with ISH may be treated to a level that uncovers sub clinical disease , and some may be overtreated . Further studies need to determine whether excessively low DBP can be prevented by more careful titration of antihypertensive therapy while maintaining SBP control . It is reassuring that patients receiving treatment for ISH never perform worse than patients receiving placebo in terms of CVD events
When the blood pressure lowering effect of beta-blockers from this review was compared to that of thiazide diuretics from our previous review ( Chen 2009 ) , second-line beta-blockers reduce systolic BP to the same extent as second-line thiazide diuretics , but reduce diastolic BP to a greater degree .
The different effect on diastolic BP means that beta-blockers have little or no effect on pulse pressure whereas thiazides cause a significant dose-related decrease in pulse pressure .
This difference in the pattern of BP lowering with beta-blockers as compared to thiazides might be the explanation for the fact that beta-blockers appear to be less effective at reducing adverse cardiovascular outcomes than thiazide diuretics , particularly in older individuals
BACKGROUND Beta-blockers are one of the more commonly prescribed classes of anti-hypertensive drugs , both as first-line and second-line .
OBJECTIVES To quantify the effect on systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , heart rate and withdrawals due to adverse effects of beta-blocker therapy when given as a second-line drug in adult patients with primary hypertension .