The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Relative value of beta blockers and thiazides for initiating antihypertensive therapy. Beta blockers or thiazides in hypertension. [Atenolol and bisoprolol in the treatment of mild and moderately severe hypertension]. Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group. Beneficial effects of switching from beta-blockers to nebivolol on the erectile function of hypertensive patients. South African hypertension guideline 2011. Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Role of High-Dose Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction and Elevated Heart Rate. Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) analyses performed up to 1992. The risk of myocardial infarction associated with antihypertensive drug therapies. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 PLACEBO-CONTROLLED TRIAL OF ATENOLOL IN TREATMENT OF PREGNANCY-ASSOCIATED HYPERTENSION The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients. Improving hypertension care in a large group-model MCO. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Initial blood pressure as a predictor of the response to antihypertensive therapy. Inpatient initiation of beta-blockade plus nurse management in vulnerable heart failure patients: a randomized study. Long-term survival and use of antihypertensive medications in older persons. Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study. A prospective, randomized, open-label, active-controlled, clinical trial to assess central haemodynamic effects of bisoprolol and atenolol in hypertensive patients Efficacy of losartan and carvedilol on central hemodynamics in hypertensives: a prospective, randomized, open, blinded end point, multicenter study
OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually Fifty-five patients with mild to moderate , renal or essential hypertension were admitted to a double blind cross-over trial of 18 weeks , involving treatment periods with placebo , the thiazide bendrofluazide ( 15 mg daily ) and the beta blocker atenolol ( 600 mg daily ) . Compared to the placebo period ( 190/117 mm Hg ) the hypotensive effect of atenolol ( -24/16 mm Hg ) was more pronounced than the hypotensive effect of bendrofluazide ( -17/6 mm Hg ) . Arguments in favor of initiating antihypertensive drug therapy with beta blocker were its more powerful hypotensive effect , the quicker onset of its action , less metabolic disturbance , decreased frequency of complaints and patient 's preference . On thiazides body weight and the frequency of swollen ankles decreased . Plasma renin concentration was not found to have a strong predicting power for the hypotensive effect of atenolol or bendrofluazide but low renin patients showed a more pronounced blood pressure decrease on bendrofluazide and high renin patients , especially essential hypertensives , on atenolol . While these points can be a guide to therapy today , the preference of one drug over the other must eventually be based on their relative efficacy in decreasing morbidity and mortality from the hypertensive disease Atenolol and bisoprolol , two beta-1-selective blockers , were compared in patients with mild and medium severe hypertension . Forty patients with a diastolic blood pressure of 95 - 115 mm Hg were two weeks after discontinuation of treatment divided at r and om into two groups treated with 50 mg atenolol and 5 mg bisoprolol . If the blood pressure was not affected by this dosage , the dose was raised to 100 mg atenolol and 10 mg bisoprolol . The blood pressure readings , heart rate , side effects of the drugs , laboratory and echocardiographic values were followed up for a period of three months . The authors recorded a marked decline of pressure and heart rate after the first week of therapy , the pressure readings in an upright position did not differ statistically from values in a sitting position , orthostatic hypotension was not recorded . The rate of success of bisoprolol was 85 % , of atenolol 75 % . During treatment no serious side-effects were observed . The biochemical parameters and echocardiographic values were not altered significantly by treatment . Atenolol and bisoprolol are two effective beta-1-selective blockers with a comparable effect in the treatment of mild and medium severe hypertension . They are useful in monotherapy as well as in combination with other antihypertensive drugs . In hypertension associated with diabetes mellitus , incipient bronchopulmonary disease and pregnancy they are also indicated . They are well tolerated also by elderly patients , an advantage of bisoprolol may be that it has a smaller impact on pressure and heart rate during the night OBJECTIVES Congestive heart failure ( CHF ) is characterized by an initial compensatory , but subsequently deleterious , activation of both the renin-angiotensin ( RAS ) and the sympathetic nervous system ( SNS ) . Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF . Carvedilol , a mixed alpha and beta-blocker with antioxidant properties , and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF . However , beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma . The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings . The aims of the present study were to examine and compare the cardiovascular , autonomic , and clinical effects of additional alpha-1 , or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF . METHODS Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics , were r and omized to 3 groups of similar demographics according to a single blind , parallel group design . The patients were aged 53 + /- 6 years , and comprised 14 men and 14 women , with a mean cardiothoracic ratio of 0.66 + /- 0.03 , and ejection fraction of 0.38 + /- 0.10 , 60 % hypertensive etiology . Group 1 patients received 5 mg enalapril alone , group 2 received 5 mg enalapril + 1 mg prazosin , and group 3 received 5 mg enalapril + 50 mg atenolol . All medication was taken daily for 4 weeks . Blood pressure , heart rate , pressure rate product , 6-minute walk test , NYHA class , and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment . Two-way repeated measures ANOVA , and a one-way ANOVA were used in data analysis . RESULTS The 3 treatments caused significant ( P<.001 ANOVA ) and similar improvements for the NYHA class ( -1.0 to -1.6 ) , and increased the 6-minute distance covered ( + 130 m to + 205 m ) . Although no treatment differences were observed , a trend suggesting a greater improvement with  enalapril + atenolol  became apparent . By the fourth week , the sympathoplegic treatments , enalapril + atenolol , and enalapril + prazosin , caused significant reductions in the pressure rate product ( -3726 + /- 1885 mm Hg x beats/min ; -3498 + /- 396 mm Hg beats/min , respectively ) , ( compared to enalapril alone ( -1349 + /- 894 mm Hg x beats/min ) ( P<.001 ANOVA ) . During the Valsalva maneuver , the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol ( 944 + /- 66 msec ) or with enalapril + prazosin ( 825 + /- 48 msec ) , compared to enalapril alone ( 760 + /- 45 msec ) ( P<.001 ANOVA ) . The phase II Valsalva tachycardia were similar between treatments . The respiratory sinus arrhythmia ratio increased significantly ( P<.005 ANOVA ) and equally on all treatments . However , the pressor and chronotropic responses to forearm isometric h and grip increased significantly on the enalapril + prazosin combination ( P<.02 ) , compared to the other treatments . CONCLUSIONS Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF , but also the result ant improvement in exercise tolerance and NYHA class . Compared to using ACE inhibition alone , the combined therapies caused a marked reduction in the pressure rate product , an index of myocardial oxygen consumption , and a greater enhancement of cardiac parasympathetic activity . Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade . Conversely , the pressor and chronotropic abnormalities during forearm isometric h and grip in CHF , were normalized by alpha-1 , but not beta-1 , blockade . Thus , the combined reflex cardiac vagal augmentation following selective beta-1 blockade , and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition , may be of major therapeutic and prognostic benefit in Blacks with non-ischemic ( hypertensive ) CHF stabilized on digoxin and diuretics The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized AIM To investigate the effect of substituting beta-blockers with nebivolol on the  erectile function of patients suffering from essential hypertension . METHODS Forty-four young and middle-aged men ( 31 - 65 years ) with essential hypertension visited our outpatient clinic and took beta-blocker treatment  ( atenolol , metoprolol or bisoprolol )  for more than 6 months . All the patients completed a question naire regarding erectile function ( International Index for Erectile Function ) . Patients were then switched to an equipotent dose of nebivolol for 3 months and , at the end of this time period , filled out the same question naire . RESULTS Twenty-nine out of the 44 ( 65.9 % ) patients who took beta-blockers ( atenolol , metoprolol or bisoprolol ) had exhibited erectile dysfunction ( ED ) . Their systolic and diastolic blood pressure did not change significantly with the treatment switch . In 20 out of these 29 ( 69 % ) patients , a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration , and in 11 of these 20 patients , erectile function was normalized . CONCLUSION Nebivolol seems to have a beneficial effect on ED ( possibly due to increased nitric oxide availability ) ; however , further prospect i ve , r and omized , placebo-controlled studies are needed to confirm the beneficial effects of nebivolol 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 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 BACKGROUND Beta-blockers in high target doses are recommended for heart failure with reduced ejection fraction ( HFrEF ) but not for preserved ejection fraction ( HFpEF ) . Treatment benefits are often more pronounced in high-risk subgroups , and patients with HFpEF with heart rate ≥70 beats per minute have emerged as such a high-risk subgroup . We examined the associations of high-dose beta-blocker use with outcomes in these patients . METHODS Of the 8462 hospitalized patients with heart failure with ejection fraction ≥50 % in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure ( OPTIMIZE-HF ) registry , 5422 had a discharge heart rate ≥70 beats per minute . Of these , 4537 had no contraindications to beta-blocker use , of which 2797 ( 2592 with dose data ) received prescriptions  for beta-blockers . Of the 2592 , 730 received high-dose beta-blockers , defined as atenolol ≥100 mg/day , carvedilol ≥50 mg/day , metoprolol tartrate or succinate ≥200 mg/day , or bisoprolol ≥10 mg/day , and 1740 received no beta-blockers . Using propensity scores for the receipt of high-dose beta-blockers , we assembled a matched cohort of 1280 patients , balanced on 58 characteristics . RESULTS All-cause mortality occurred in 63 % and 68 % of matched patients receiving high-dose beta-blocker vs no beta-blocker , respectively , during 6 years ( median , 2.8 ) of follow-up ( hazard ratio , 0.86 ; 95 % confidence interval , 0.75 - 0.98 ; P = .027 ) . The hazard ratios ( 95 % confidence intervals ) for all-cause readmission and the combined endpoint of all-cause readmission or all-cause mortality associated with high-dose beta-blocker use were 0.90 ( 0.81 - 1.02 ) and 0.89 ( 0.80 - 1.00 ) , respectively . CONCLUSIONS In patients with HFpEF and heart rate ≥70 beats per minute , high-dose beta-blocker use was associated with a significantly lower risk of death . Future r and omized controlled trials are needed to examine this association Hypertension is increasingly common with advancing age and a risk factor for all kinds of cardiovascular complications . Moreover , cardiovascular disease is a major cause of morbidity and mortality in the elderly . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was set up by the Swedish Hypertension Society to investigate the value of antihypertensive treatment in the elderly . In this placebo controlled r and omised prospect i ve study 1,627 men and women aged 70 - 84 years with a supine blood pressure > or = 180/105 mmHg ( and /or ) but not isolated systolic hypertension participated . Three beta-blockers and one diuretic were used as blood pressure lowering agents and the average follow-up in the study was 25 months ( 3,390 patient-years ) . Administration of active antihypertensive therapy , reduced supine blood pressure from 195/102 mmHg to 167/87 mmHg at longest follow-up in comparison with placebo . A majority of the patients needed combined treatment to reach the goal blood pressure ( 160/95 mmHg ) . Associated with a fall in blood pressure were significant reductions in all cardiovascular primary endpoints ( -40 % , p = 0.0031 ) , in fatal and non-fatal stroke ( -47 % , p = 0.0081 ) and in total mortality ( -43 % , p = 0.0079 ) . In addition to the substantial effects on primary endpoints active treatment also showed clinical ly relevant effects on secondary endpoints ( e.g. heart failure ) . The impact on cardiovascular morbidity and mortality with antihypertensive treatment in this elderly cohort was greater than previously seen in middle-aged hypertensive patients , with maintained tolerability and a favourable cost-effectiveness ratio . Finally , women benefited from treatment at least as much as men OBJECTIVE To assess the association between  first myocardial infa rct ion and the use of antihypertensive agents .  DESIGN AND SETTING We conducted a population -based case-control study among enrollees of the Group Health Cooperative of Puget Sound ( GHC ) . PATIENTS AND METHODS Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infa rct ion from 1986 through 1993 among women and from 1989 through 1993 among men . Controls were a stratified r and om sample of hypertensive GHC enrollees , frequency matched to the cases on age , sex , and calendar year . All 623 cases and 2032 controls had pharmacologically treated hypertension . Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors . Antihypertensive therapy was assessed using the GHC 's computerized pharmacy data base . RESULTS The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease . Compared with users of diuretics alone , the adjusted risk ratio of myocardial infa rct ion was increased by about 60 % among users of calcium channel blockers with or without diuretic ( risk ratio = 1.62 % ; 95 % confidence interval [ Cl ] , 1.11 to 2.34 ; P = .01 ) . The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker .  Among these subjects , the use of calcium channel blockers compared with beta-blockers was associated with about a 60 % increase in the adjusted risk of myocardial infa rct ion ( risk ratio = 1.57 ; 95 % Cl , 1.21 to 2.04 ; P < .001 ) . While high doses of beta-blockers were associated with a decreased risk of myocardial infa rct ion ( trend P = .04 ) , high doses of calcium channel blockers were associated with an increased risk ( trend P < .01 ) . CONCLUSIONS In this study of hypertensive patients , the use of short-acting calcium channel blockers , especially in high doses , was associated with an increased risk of myocardial infa rct ion . Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies , including calcium channel blockers , on several important cardiovascular end points . Until these results are available , the findings of this study support the current guidelines from the Joint National Committee on the Detection , Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated , unacceptable , or not tolerated Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension Atenolol was compared with placebo in a r and omised and double-blind prospect i ve study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest .  Atenolol given once daily significantly reduced blood-pressure , prevented proteinuria , and reduced the number of hospital admissions . Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group , whose babies had a high morbidity . Respiratory distress syndrome occurred only in the placebo group . Intrauterine growth retardation , neonatal hypoglycaemia , and hyperbilirubinaemia occurred with the same frequency in the two groups . Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups . There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy . Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually 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 The effectiveness of a quality improvement program for hypertension management practice s and patient health outcomes in a group-model managed care organization was evaluated . Health-system pharmacists analyzed medical and pharmacy cl aims data to identify hypertensive patients . Chart review was conducted on a r and om sample of these patients to vali date a hypertension diagnosis and to obtain blood pressure ( BP ) control rates and prevalence of cardiovascular risk factors and comorbid conditions . The interventions consisted of educating health care providers and recommending appropriate pharmacotherapy for compelling indications . Patient outcomes were compared with baseline hypertension data . After interventions were implemented , medical and pharmacy cl aims identified 30,721 hypertensive patients and chart review s were performed on a r and om sample of 417 patients . Pharmacy cl aims revealed a total of 193,311 antihypertensive prescriptions . Approximately 47 % of all hypertensive patients were managed with monotherapy , while 24 % received dual therapy , and 11 % were taking three or more antihypertensive medications per day . Of the patients on monotherapy , 93 % received an angiotensin-converting-enzyme inhibitor ( 27.3 % ) , diuretic ( 26.6 % ) , beta-blocker ( 23.4 % ) , or calcium channel blocker ( 15.4 % ) . The overall level of BP control significantly improved from 37.2 % at baseline to 49.2 % at follow-up ( p = 0.0007 ) . BP control in the follow-up evaluation was 22.2 % in diabetic patients . For treatment of patients with comorbid disease states , provider practice patterns were evaluated at baseline and follow-up . Improving the quality of hypertension management increased BP control from 37.2 % to 49.2 % . Continued efforts to improve hypertension management , particularly in patients with concomitant diabetes and in elderly patients with isolated systolic hypertension , are needed 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 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 BACKGROUND Predischarge beta-blocker initiation in hospitalized patients with heart failure due to reduced left ventricular ejection fraction ( LVEF ) is safe and improves adherence ; improved outcomes with this approach have not been demonstrated in a r and omized trial . This study compared 6-month rehospitalization rates among patients assigned to predischarge beta-blockade coupled with postdischarge nurse management ( intervention ) versus usual care . METHODS AND RESULTS We r and omized 64 patients with an LVEF < /=0.40 to low-dose carvedilol coupled with nurse management or usual care .  The nurse manager saw patients within 2 weeks of discharge , then biweekly until stable . Baseline characteristics reflected a vulnerable population ( 80 % uninsured , 72 % minorities , 80 % unemployed or disabled ) , as did heart failure etiology ( 28 % substance abuse , 27 % ischemic , 19 % hypertension , 17 % idiopathic ) . Mean baseline LVEF was 0.23 in both groups . Among intervention patients at 6 -months , beta-blocker utilization was higher ( 96 vs. 48 % , P < .001 ) , mean New York Heart Association class improved ( -1.44 vs. -0.77 , P = .01 ) , and total heart failure rehospitalizations were reduced by 84 % ( 3 vs. 19 , P = .02 ) . A trend toward improved LVEF was also observed ( + 16 vs. + 11 units , P = .17 ) . CONCLUSION Inpatient beta-blocker initiation coupled with nurse management improved outcomes among sociodemographically disadvantaged heart failure patients . Our results support a practice shift toward inpatient beta-blocker initiation with structured outpatient follow-up OBJECTIVE To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors  have a different risk of mortality than those using beta-blockers . DESIGN A prospect i ve cohort study continuing from 1988 through 1992 . SETTING Three communities of the Established Population s for Epidemiologic Studies of the Elderly . PARTICIPANTS Hypertensive participants aged > or = 71 years ( n = 906 ) who had no evidence of congestive heart failure and who were using either beta-blockers ( n = 515 ) , verapamil ( n = 77 ) , diltiazem ( n = 92 ) , nifedipine ( n = 74 ) , or ACE inhibitors ( n = 148 ) .  Nifedipine was of the short acting variety . MEASUREMENTS The main outcome measure was all-cause mortality . Age , gender , smoking , HDL-cholesterol , blood pressure , intake of digoxin and diuretics , physical disability , self-perceived health , and comorbid conditions were examined as confounders . RESULTS During 3538 person-years of follow-up , 188 participants died ( 53 deaths per 1000 person-years ) . Compared with beta-blockers , after adjusting for age , gender , comorbid conditions and other health-related factors , the relative risks ( 95 % confidence interval ) for mortality associated with use of verapamil , diltiazem , nifedipine , and ACE inhibitors were 0.8 ( 0.4 - 1.4 ) , 1.3 ( 0.8 - 2.1 ) , 1.7 ( 1.1 - 2.7 ) , and 0.9 ( 0.6 - 1.4 ) , respectively . The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics . Higher doses of nifedipine were associated with higher mortality . CONCLUSION Compared with beta-blockers , use of short acting nifedipine was associated with decreased survival in older hypertensive persons . However , selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted , and final conclusions will depend on clinical trials In a r and omized primary prevention trial including 3,234 men with mild to moderate uncomplicated hypertension , the effect of the beta-blocker metoprolol or a thiazide diuretic as an initial antihypertensive therapy was compared regarding the risk of sudden cardiovascular death during a follow-up ranging from 2.3 to 10.8 years ( median of 4.2 years ) . Only men aged 40 to 64 years were included in the study . The r and omization of patients into the metoprolol ( n = 1,609 ) or diuretic group ( n = 1,625 ) was performed after stratification for age , smoking habits , serum cholesterol , and systolic blood pressure . At baseline the two treatment groups were well matched . Metoprolol was given in a mean dose of 174 mg daily and the mean dose of thiazide diuretic was either 46 mg hydrochlorothiazide daily or 4.4 mg bendroflumethiazide daily . Identical blood pressure control was achieved using the fixed therapeutic schedule . Total and cardiovascular mortality were significantly lower for metoprolol than for diuretics , owing to fewer deaths from coronary heart disease and stroke . Of the cardiovascular deaths , 78 % were classified as sudden cardiovascular deaths ( occurred within 24 h after the onset of symptoms ) . There were significantly fewer sudden cardiovascular deaths in the metoprolol group compared to the diuretic group ( 32 v 45 , P = .017 ) . The present results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of sudden cardiovascular deaths than initial diuretic treatment in uncomplicated hypertension Objective : The results from the ASCOT CAFÉ study demonstrated the inferiority of beta blockers in reducing central aortic blood pressure . In this study , we wanted to demonstrate whether or not second-generation beta blockers with higher beta 1 selectivity , namely bisoprolol , may counterbalance the effect of bradycardia through reduced reflection wave magnitude result ing from the relative lack of increase in peripheral vascular resistance . Method : This was a prospect i ve , r and omized , open-label , active-controlled trial in 209 hypertensive patients to evaluate the effect of bisoprolol and atenolol on aortic pulse pressure . Patients received a once-daily 5 mg dose of bisoprolol ( n = 96 ) or 50 mg dose of atenolol ( n = 95 ) at baseline with titration up to bisprolol 10 mg and atenolol 100 mg allowed at the 4th week when the brachial blood pressure was above treatment goal ( average dose : bisoprolol : 5.4 mg , atenolol : 52.8 mg ) . Central blood pressure and augmentation index were measured at baseline and 12 weeks later , by pulse wave analysis with radial artery tonometry . The primary endpoint of the study was the difference in the central pulse pressure ( CPP ) at 12 weeks . Results : The results showed a significant reduction of CPP in both groups at week 12 of administration compared with the predose level ( P < 0.05 ) ; however , there was no significant difference in terms of CPP change  [ bisoprolol ( baseline CPP 47.49 ± 11.33 , follow-up 43.09 ± 11.67 ) vs. atenolol ( baseline CPP 45.93 ± 11.62 , follow-up 42.23 ± 9.92 ) , P = 0.594 ] . Conclusion : In this study , there was no significant difference between bisoprolol and atenolol in terms of reduction of aortic pulse pressure after 12 weeks of treatment 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
SBP-lowering effects were significantly increased for bisoprolol compared with placebo .
In conclusion , current evidence does not support carvedilol or bisoprolol as first-line therapy for adult hypertension without compelling indications
Although beta blockers have been used as initial therapy for ischemic heart diseases and heart failure , the beneficial effects of beta blockers are controversial compared with other antihypertensive agents as initial therapy for hypertension without compelling indications .
Moreover , atenolol has been most commonly used with beta blockers .
The objective of the present systematic review associated with the Japanese Society of Hypertension ( JSH ) 2019 Hypertension Guideline ( Clinical Question 6 ) was to assess the outcomes ( cardiocerebrovascular mortality , total cause mortality , hypotension , bradycardia , other adverse effects , and changes in systolic blood pressure ( SBP ) ) of currently used carvedilol and bisoprolol as initial therapy for adult hypertension without compelling indications .