The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. The risk of myocardial infarction associated with antihypertensive drug therapies. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Effect of beta-blockers on the mortality of Japanese patients with myocardial infarction. Mortality benefit of beta-blockade after successful elective percutaneous coronary intervention. Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction Beta-adrenergic blockade after stroke. A preliminary closed cohort study. Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Management of essential hypertension in patients with different degrees of left ventricular hypertrophy. Multicenter trial. Impact of nonfatal myocardial infarction on outcomes in patients with advanced heart failure and the effect of bucindolol therapy. Effects of propranolol on recovery of heart rate variability following acute myocardial infarction and relation to outcome in the Beta-Blocker Heart Attack Trial. Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction. Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction. Should nephrologists use beta-blockers? A perspective. STOP-Hypertension--preliminary communication from the pilot study of the Swedish Trial in Old Patients with Hypertension. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group. Are beta-blockers effective in elderly patients who undergo coronary revascularization after acute myocardial infarction?
OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually OBJECTIVE To assess the association between  first myocardial infa rct ion and the use of antihypertensive agents .  DESIGN AND SETTING We conducted a population -based case-control study among enrollees of the Group Health Cooperative of Puget Sound ( GHC ) . PATIENTS AND METHODS Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infa rct ion from 1986 through 1993 among women and from 1989 through 1993 among men . Controls were a stratified r and om sample of hypertensive GHC enrollees , frequency matched to the cases on age , sex , and calendar year . All 623 cases and 2032 controls had pharmacologically treated hypertension . Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors . Antihypertensive therapy was assessed using the GHC 's computerized pharmacy data base . RESULTS The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease . Compared with users of diuretics alone , the adjusted risk ratio of myocardial infa rct ion was increased by about 60 % among users of calcium channel blockers with or without diuretic ( risk ratio = 1.62 % ; 95 % confidence interval [ Cl ] , 1.11 to 2.34 ; P = .01 ) . The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker .  Among these subjects , the use of calcium channel blockers compared with beta-blockers was associated with about a 60 % increase in the adjusted risk of myocardial infa rct ion ( risk ratio = 1.57 ; 95 % Cl , 1.21 to 2.04 ; P < .001 ) . While high doses of beta-blockers were associated with a decreased risk of myocardial infa rct ion ( trend P = .04 ) , high doses of calcium channel blockers were associated with an increased risk ( trend P < .01 ) . CONCLUSIONS In this study of hypertensive patients , the use of short-acting calcium channel blockers , especially in high doses , was associated with an increased risk of myocardial infa rct ion . Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies , including calcium channel blockers , on several important cardiovascular end points . Until these results are available , the findings of this study support the current guidelines from the Joint National Committee on the Detection , Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated , unacceptable , or not tolerated BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death OBJECTIVE The Captopril Prevention Project ( CAPPP ) evaluated the effects of an ACE inhibitor-based therapeutic regimen on  cardiovascular mortality and morbidity in hypertension .  One planned sub analysis of the CAPPP was to evaluate the outcome in the diabetic patient group . RESEARCH DESIGN AND METHODS In the CAPPP , 572 ( 4.9 % of 10,985 hypertensive patients ) had diabetes at baseline and were studied according to a prospect i ve , r and omized , open , blinded , end point trial design . Patients aged 25 - 66 years with diastolic blood pressure > or = 100 mmHg were included and r and omized to receive either captopril or conventional antihypertensive treatment ( diuretics and /or beta-blockers ) . RESULTS The primary end point , fatal and nonfatal myocardial infa rct ion and stroke as well as other cardiovascular deaths , was markedly lower in the captopril than in the conventional therapy group ( relative risk [ RR ] = 0.59 ; P = 0.018 ) . Specifically , cardiovascular mortality , defined as fatal stroke and myocardial infa rct ion , sudden death , and other cardiovascular death , tended to be lower in the captopril group ( RR = 0.48 ; P = 0.084 ) , and no difference was observed between the study groups for stroke ( RR = 1.02 ; P = 0.96 ) . Myocardial infa rct ions were less frequent in the captopril group than in the conventional therapy group ( RR = 0.34 ; P = 0.002 ) . Furthermore , total mortality was lower in the captopril as compared with the conventional therapy group ( RR = 0.54 ; P = 0.034 ) . Patients with impaired metabolic control seemed to benefit the most from ACE inhibitor-based therapy . CONCLUSIONS Captopril is superior to a diuretic/beta-blocker antihypertensive treatment regimen in preventing cardiovascular events in hypertensive diabetic patients , especially in those with metabolic decompensation BACKGROUND After a myocardial infa rct ion , a higher prevalence of coronary vasospastic response has been reported in the Japanese population than in the Caucasian population . Beta-blockers may exacerbate coronary vasospasm . However , beta-blockers are given to Japanese patients after an acute myocardial infa rct ion , though the mortality benefit is unknown . Thus , we investigated the mortality benefit of beta-blockers given to Japanese patients after an acute myocardial infa rct ion . METHODS We prospect ively studied consecutive patients with a first myocardial infa rct ion admitted to the coronary care unit of Kansai Medical University Hospital , Osaka , Japan from May 1994 through the end of 2001 . Patients who died during hospitalization or who were referred for coronary artery bypass graft surgery were excluded . The association of beta-blocker use with mortality after discharge was assessed by a proportional hazards regression analysis . RESULTS There were 546 patients and 400 ( 73.3 % ) patients were treated with beta-blockers  at the time of discharge from hospital . During a mean follow-up of 2 years , 46 ( 8.4 % ) patients died . Beta-blocker therapy was associated with a reduced mortality after adjustment for age , gender , Q wave myocardial infa rct ion , reperfusion therapy during acute phase , Killip functional class , serum creatinine level , cardiovascular risk factors , and medications ( hazard ratio=0.51 , 95 % confidence interval=0.27 to 0.95 ) . CONCLUSIONS Contrary to the concern that beta-blocker therapy might induce coronary vasospasm and reduce survival , beta-blocker therapy improved survival after discharge in Japanese patients with a first myocardial infa rct ion OBJECTIVES The goal of this study was to evaluate the mortality benefit of beta-blockers  after successful percutaneous coronary intervention ( PCI ) . BACKGROUND Beta-blockers reduce mortality after myocardial infa rct ion ( MI ) , though limited data are available regarding their role after successful PCI . METHODS Each year from 1993 through 1999 , the first 1,000 consecutive patients undergoing PCI  were systematic ally followed up . Patients presenting with acute or recent MI , shock , or unsuccessful revascularization procedures were excluded from the analysis . Clinical , procedural , and follow-up data of beta-blocker-treated and non-beta-blocker-treated patients were compared . A multivariate survival analysis model using propensity analysis was used to adjust for heterogeneity between the two groups . RESULTS Of the 4,553 patients , 2,056 ( 45 % ) were treated with beta-blockers at the time of the procedure . Beta-blocker therapy was associated with a mortality reduction from 1.3 % to 0.8 % at 30 days ( p = 0.13 ) and a reduction from 6.0 % to 3.9 % at one year ( p = 0.0014 ) . This survival benefit of beta-blockers was independent of left ventricular function , diabetic status , history of hypertension , or history of MI . Using propensity analysis , beta-blocker therapy remained an independent predictor for one-year survival after PCI ( hazard ratio , 0.63 ; 95 % confidence interval , 0.46 to 0.87 ; p = 0.0054 ) . CONCLUSIONS Within this large prospect i ve registry , beta-blocker use was associated with a marked long-term survival benefit among patients undergoing successful elective percutaneous coronary revascularization A multicenter , r and omized , controlled , double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone , for the long-term management of middle-aged adults with " mild " hypertension . Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population ; mild hypertension 's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall ; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy , and other trials that failed to demonstrate beneficial impact on morbidity and mortality , possibly due to residual questions concerning aspects of benefit to risk ratios with these medications ; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means ; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors , angiotensin converting enzyme inhibitors and calcium channel blockers ; paucity of data from trials on long-term combined effects of diet and drug therapy , and of diet alone , for people with mild hypertension . During the next few years , phase 1 of the trial will study 6 groups of drugs . The step-1 drugs are angiotensin converting enzyme inhibitor ( enalapril ) , alpha 1 inhibitor ( doxazosin ) , beta blocker ( acebutolol ) , calcium channel blocker ( amlodipine ) , diuretic ( chlorthalidone ) and placebo . All participants are to receive vigorous sustained nutritional counseling to reduce obesity , moderate sodium intake and avoid heavy use of alcohol . Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension , side effects ( i.e. , clinical and biochemical ) and consequent need to discontinue drug and quality of life . Phase-1 data are to be used to complete the phase-2 design , with the ultimate aim to assess effects on morbidity and mortality The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infa rct ion ( AMI ) .  Primary percutaneous coronary intervention ( PCI ) , which has become the mainstay of treatment for AMI , is associated with a lower mortality than fibrinolysis . The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear . We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure . The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infa rct ion ( ALPS-AMI ) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infa rct ion . We prospect ively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients ( median age 66 years ; 18.2 % women ) who had Killip class 1 on admission and were discharged alive . The primary endpoint was all-cause mortality . The 3-year follow-up was completed in 413 patients ( 93.0 % ) . During this follow-up , 21 patients ( 4.7 % ) died . In Kaplan – Meier analysis , patients on beta-blockers had a significantly lower incidence of all-cause mortality ( 2.7 vs. 7.3 % , log-rank p = 0.025 ) . After adjusting for the calculated propensity score for using beta-blockers , their use remained an independent predictor of all-cause mortality ( hazard ratio 0.309 ; 95 % confidence interval 0.116–0.824 ; p = 0.019 ) . In the statin era , the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission To collect background data for a prospect i ve clinical trial of beta-blocking agents in the prevention of deaths after stroke , the long-term prognosis in 60 patients discharged from a stroke unit on beta-blocker therapy  was compared with the outcome in 60 matched patients with stroke but without beta-blockers .  Matching included sex , age , type of stroke , and presence or absence of hypertension and cardiac failure . Thirteen patients ( 22 % ) in the beta-blocker group died during a median followup of 41 months . Of the 60 patients not on beta-blockade at discharge , 21 ( 35 % ) died during a median followup of 36 months . By life-table technique and log-rank test , the relative risk for death was 0.60:1.00 ( p = 0.14 ) . During followup , 12 recurrent strokes were observed in patients on beta-blockers and 19 in patients without beta-blockers ( relative risk 0.57:1.00 ; p = 0.12 ) . It appeared that the reduction in mortality could only marginally be ascribed to fewer deaths from myocardial infa rct ion ; other causes of death were also less frequent in beta-blocker-treated patients . The results emphasize that supplementary information on the effect of beta-blocking agents on mortality after stroke is needed before a larger trial of beta-blocker therapy in patients with manifest cerebrovascular disease can be initiated This retrospective , nonr and omized analysis evaluated the effect of initiating statin or beta-blocker treatment early in the course of heart failure developed during acute myocardial infa rct ion compared with the effect of neither or both treatments . Early initiation of statins or beta blockers alone was associated with improved event-free survival , and the benefits of the combined treatment were additive OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually Three hundred and four hypertensive patients with different degrees of left ventricular hypertrophy ( LVH ) were recruited and followed for 4 years . The patients were r and omized into two groups : Group I ( 150 patients ) was treated with a combination of hypotensive drugs including beta-blockers , and group II ( 154 patients ) was treated with the same combination of drugs including diuretics instead of beta-blockers . By the end of the fourth year , 60 endpoints were recorded : 17 strokes , 13 myocardial infa rct ions , and 30 cases of chronic coronary insufficiency . Mortality was statistically higher in group II ( 7 of 154 or 5 % v 1 of 150 or 1 % ) ( P less than .035 ) , but there was no difference between the groups in the incidence of nonfatal endpoints . These data confirm that beta-blockers can reduce mortality associated with the complications presented in hypertensive patients . Increased left ventricular myocardial mass ( greater than 200 g , according to Teichholz ' formula ) was shown to have prognostic value for the development of complications . In patients with LVMM greater than 200 g , the probability of fatal complications was higher ( P less than .007 ) , as was the probability of nonfatal myocardial infa rct ion ( P less than .01 ) , development of coronary artery disease ( P less than .02 ) , and all complications ( P less than .0003 ) . Regression of LVH to less than 200 g ( according to Teichholz ' formula ) improved prognosis We sought to identify the clinical characteristics and outcomes of patients who had advanced heart failure and nonfatal myocardial infa rct ion ( MI ) in the beta-Blocker Evaluation of Survival Trial ( BEST ) and to investigate whether bucindolol alters the risk of developing nonfatal MI . Of the 2,708 patients enrolled in the study , 142 had suspected MI and 69 had confirmed MI ; there were 860 deaths overall . The rate of nonfatal MI in the BEST was low over the 4.1 years of follow-up ( 4.8 % had suspected events and 2.4 % had adjudicated events ) and was similar to that in high-risk population s. Cox 's proportional hazard model with 23 prespecified c and i date variables associated advanced age , heart failure symptoms , male gender , ischemic etiology , diabetes , and hypertension with nonfatal MI or cardiovascular death . The 2-year mortality rate was 56 % for the cohort that had suspected nonfatal MI versus 30 % for the cohort that did not ( p = 0.01 ) . Likewise , the risk of hospitalization for congestive heart failure was twofold greater . Beta-blocker therapy with bucindolol result ed in a 52 % decrease in suspected nonfatal MI ( 2.9 % vs 5.5 % , p = 0.001 ) . In conclusion , nonfatal MI occurs at low rates but increases the risks for mortality and hospitalization in patients who have advanced heart failure . Beta-blocker therapy with bucindolol appears to attenuate the risk of nonfatal MI in this population This study evaluated the effects of propranolol on recovery of heart rate variability ( HRV )  after acute myocardial infa rct ion and its relation to outcome in the Beta-blocker Heart Attack Trial ( BHAT ) . Beta blockers improve mortality after acute myocardial infa rct ion , but through an unknown mechanism . Depressed HRV , a measure of autonomic tone , predicts mortality after acute myocardial infa rct ion . Whether beta blockers influence recovery of HRV after acute myocardial infa rct ion , and thereby improve outcome , is unknown . We compared 24-hour HRV parameters at 1 week after acute myocardial infa rct ion and after 6 weeks of treatment with  propanolol ( n = 88 ) or placebo ( n = 96 ) . The relation between 25-month outcome ( death/acute myocardial infa rct ion/congestive heart failure ) , propranolol treatment , and HRV was further analyzed . After 6 weeks , high-frequency ( HF ) power ( log-normalized ) , an index of vagal tone , increased more in propranolol-treated  patients ( 4.28 + /- 0.1 to 5.17 + /- 0.09 ms(2 ) ) than in placebo-treated patients ( 4.26 + /- 0.09 to 4.77 + /- 0.1 ms(2 ) , p < 0.05 ) . Sympathovagal balance measured by the low-frequency ( LF ) to HF ratio increased in placebo-treated patients ( 3.55 + /- 0.24 to 3.86 + /- 0.24 ) but decreased in those treated with propranolol ( 3.76 + /- 0.29 to 3.17 + /- 0.23 , p < 0.01 ) . Other frequency-domain parameters increased over time but were not affected by propranolol . Propranolol blunted the morning increase in the LF/HF ratio . Recovery of HF , the strongest HRV predictor of outcome , and propranolol therapy independently predicted outcome . In summary , after acute myocardial infa rct ion , propranolol therapy improves recovery of parasympathetic tone , which correlates with improved outcome , and decreases morning sympathetic predominance . These findings may eluci date the mechanisms by which beta blockers decrease mortality and reduce the early morning risk of sudden death after acute myocardial infa rct ion OBJECTIVES To study determinants and adverse outcomes ( mortality and rehospitalization ) of beta-blocker underuse in elderly patients with myocardial infa rct ion ; and whether the relative risks ( RRs ) of survival associated with beta-blocker use were comparable to those reported in the large r and omized controlled trials ( RCTs ) . SETTING New Jersey Medicare population . DESIGN Retrospective cohort design using linked Medicare and drug cl aims data from 1987 to 1992 . PATIENTS Statewide cohort of 5332 elderly 30-day acute myocardial infa rct ion ( AMI ) survivors with prescription drug coverage , of whom 3737 were eligible for beta-blockers .  MAIN OUTCOME MEASURES beta-Blocker and calcium channel blocker use in the first 90 days after discharge and mortality rates and cardiac hospital readmissions over the 2-year period after discharge , controlling for sociodemographic and baseline risk variables . RESULTS Only 21 % of eligible patients received beta-blocker therapy ; this rate remained unchanged from 1987 to 1991 . Patients were almost 3 times more likely to receive a new prescription for a calcium channel blocker than for a new beta-blocker after their AMIs . Advanced age and calcium channel blocker use predicted underuse of beta-blockers . Controlling for other predictors of survival , the mortality rate among beta-blocker recipients was 43 % less than that for nonrecipients ( RR=0.57 ; 95 % confidence interval [ CI ] , 0.47 - 0.69 ) . Effects on mortality were substantial in all age strata ( 65 - 74 years , 75 - 84 years , and > or = 85 years ) and consistent with the results for elderly subgroups of 2 large RCTs . beta-Blocker recipients were rehospitalized 22 % less often than nonrecipients ( RR=0.78 ; 95 % CI , 0.67 - 0.90 ) . Use of a calcium channel blocker instead of a beta-blocker was associated with a doubled risk of death ( RR= 1.98 ; 95 % CI , 1.44 - 2.72 ) , not because calcium channel blockers had a demonstrable adverse effect , but because they were substitutes for beta-blockers . CONCLUSIONS beta-Blockers are underused in elderly AMI survivors , leading to measurable adverse outcomes . These data suggest that the survival benefits of beta-blockade after an AMI may extend to eligible patients older than 75 years , a group that has been excluded from RCTs BACKGROUND Beta-blocker therapy after acute myocardial infa rct ion ( MI ) improves survival .  Beta-blocker doses used in clinical practice are often substantially lower than those used in the r and omized trials establishing their efficacy . OBJECTIVES This study evaluated the association of beta-blocker dose with survival after acute MI , hypothesizing that higher dose beta-blocker therapy will be associated with increased survival . METHODS A multicenter registry enrolled 7,057 consecutive patients with acute MI . Discharge beta-blocker dose was indexed to the target beta-blocker doses used in r and omized clinical trials , grouped as > 0 % to 12.5 % , > 12.5 % to 25 % , > 25 % to 50 % , and > 50 % of target dose . Follow-up vital status was assessed , with the primary endpoint of time-to-death right-censored at 2 years . Multivariable and propensity score analyses were used to account for group differences . RESULTS Of 6,682 patients with follow-up ( median 2.1 years ) , 91.5 % were discharged on a beta-blocker ( mean dose 38.1 % of the target dose ) . Lower mortality was observed with all beta-blocker doses ( p < 0.0002 ) versus no beta-blocker therapy . After multivariable adjustment , hazard ratios for 2-year mortality compared with the > 50 % dose were 0.862 ( 95 % confidence interval [ CI ] : 0.677 to 1.098 ) , 0.799 ( 95 % CI : 0.635 to 1.005 ) , and 0.963 ( 95 % CI : 0.765 to 1.213 ) for the > 0 % to 12.5 % , > 12.5 % to 25 % , and > 25 % to 50 % of target dose groups , respectively . Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome . CONCLUSIONS These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous r and omized clinical trials compared with lower doses . These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy . ( The PACE-MI Registry Study - Outcomes of Beta-blocker Therapy After Myocardial Infa rct ion [ OBTAIN ] : NCT00430612 ) Given the high prevalence of cardiovascular disease in people with chronic kidney disease ( CKD ) and the clear benefits of mortality reduction observed for most β−blockers in clinical trials , they are relatively underused in CKD patients [ 1,2 ] . The rationale for use of β-blockers in patients with CKD is review ed in detail elsewhere [ 2,3 ] but is summarized in this editorial . Alterations in β- and α-receptor responsiveness are associated with sympathetic over-activity in CKD . This increased sympathetic activity is involved in the genesis of hypertension , and contributes to cardiac complications seen in CKD [ 2,3 ] . The contribution of the sympathetic nervous system to nephropathy progression is documented in sub-totally nephrectomized rats where non-hypotensive doses of β-blockers ameliorate development of glomerulosclerosis and cardiac injury [ 4 ] . In men ,  sympathetic over-activity  , as assessed by sural nerve microneurography , was present in patients on haemodialysis [ 5 ] , stage 4 nephropathy [ 6 ] and in early stage 2 nephropathy among patients with polycystic kidney disease [ 7 ] . The role of the damaged kidney in causing sympathetic over-activity is illustrated by normalization of sympathetic over-activity in haemodialysis patients following bilateral nephrectomy [ 5 ] and in renal allograft recipients when their shrunken native kidneys are removed [ 8 ] . The most common cause of death in stage 3 and higher CKD results from complications of cardiovascular disease . This may be due , in part , to inadequate treatment of blood pressure , where blood pressure goals were not attained and agents known to reduce mortality secondary to cardiovascular causes , i.e. aspirin , ACE inhibitors and β-blockers were not used [ 9 ] . In a separate study , β-blockers were used in fewer than 30 % of haemodialysis patients [ 10 ] . This is surprising , since β-blockers are well-established , evidence -based therapy for reducing cardiovascular risk in hypertension associated with diabetes and after myocardial infa rct ion [ 11,12 ] . Observational studies support definite survival benefits derived from β-blocker use in patients with advanced CKD [ 13,14 ] . Furthermore , a prospect i ve The Swedish trial in old patients with hypertension ( STOP-Hypertension ) is a multicentre , r and omized , double-blind study of beta-blockers/diuretics versus placebo in old hypertensives . Primary end-points are stroke and myocardial infa rct ion ( fatal and non-fatal ) as well as other cardiovascular mortality . To evaluate the logistics of STOP-Hypertension , a pilot study was carried out . All patients aged 70 - 84 years in 31 centres were consecutively registered in a log-book . Altogether 4668 patients were screened : 41.5 % had previously been treated for hypertension and 13.5 % had blood pressures greater than or equal to 180/105 mmHg . Thus , 55 % were ' hypertensive ' . In all , 465 patients ( 18 % of the ' hypertensive ' patients ) started a 3-month washout period ( previously treated , n = 396 ) or a 4-week run-in period ( previously untreated , n = 69 ) period . The most frequent reasons for not starting the run-in/washout were other indications for treatment with beta-blockers/diuretics ( 13 % ) , unwillingness to participate ( 8 % ) or isolated systolic hypertension ( 4 % ) . The pilot study was evaluated after 1 year : 89 patients ( 1.9 % ) had been r and omized , 66 patients ( 1.4 % ) were still in the run-in/washout period and the majority of the remaining patients were not r and omized because they had not reached the inclusion blood pressure ( greater than or equal to 180 mmHg systolic and /or greater than or equal to 105 mmHg diastolic ) following withdrawal of their antihypertensive medication . During the run-in/washout period there were few serious clinical events : one case of myocardial infa rct ion , three patients had strokes ( two fatal ) , 10 developed congestive heart failure , three tachyarrhythmia and two pneumonia ( one fatal ) . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension BACKGROUND The beneficial effects of beta-blockers on long-term outcome after acute myocardial infa rct ion were shown before the introduction of thrombolysis and angiotensin-converting-enzyme ( ACE ) inhibitors . Generally , the patients recruited to these trials were at low risk : few had heart failure , and none had measurements of left-ventricular function taken . We investigated the long-term efficacy of carvedilol on morbidity and mortality in patients with left-ventricular dysfunction after acute myocardial infa rct ion treated according to current evidence -based practice . METHODS In a multicentre , r and omised , placebo-controlled trial , 1959 patients with a proven acute myocardial infa rct ion and a left-ventricular ejection fraction of < /=40 % were r and omly assigned 6.25 mg carvedilol ( n=975 ) or placebo ( n=984 ) . Study medication was progressively increased to a maximum of 25 mg twice daily during the next 4 - 6 weeks , and patients were followed up until the requisite number of primary endpoints had occurred . The primary endpoint was all-cause mortality or hospital admission for cardiovascular problems . Analysis was by intention to treat . FINDINGS Although there was no difference between the carvedilol and placebo groups in the number of patients with the primary endpoint ( 340 [ 35 % ] vs 367 [ 37 % ] , hazard ratio 0.92 [ 95 % CI 0.80 - 1.07 ] ) , all-cause mortality alone was lower in the carvedilol group than in the placebo group ( 116 [ 12 % ] vs 151 [ 15 % ] , 0.77 [ 0.60 - 0.98 ] , p=0.03 ) . Cardiovascular mortality , non-fatal myocardial infa rct ions , and all-cause mortality or non-fatal myocardial infa rct ion were also lower on carvedilol than on placebo . INTERPRETATION In patients treated long-term after an acute myocardial infa rct ion complicated by left-ventricular systolic dysfunction , carvedilol reduced the frequency of all-cause and cardiovascular mortality , and recurrent , non-fatal myocardial infa rct ions . These beneficial effects are additional to those of evidence -based treatments for acute myocardial infa rct ion including ACE inhibitors BACKGROUND Previous prospect i ve outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure . AIM The primary objective is to determine whether rosuvastatin ( 10 mg ) reduces the combined endpoint of cardiovascular mortality , non-fatal myocardial infa rct ion or non-fatal stroke ( time to first event ) . The first secondary endpoint is all-cause mortality . METHODS CORONA is a r and omized , double-blind , placebo-controlled trial . Briefly , men and women , aged > or = 60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or = 0.40 ( NYHA class III and IV ) or < or = 0.35 ( NYHA class II ) were eligible if they were not using or in need of cholesterol lowering drugs .  RESULTS Mean age was 73 years ( n=5016 ; 24 % women ) , with 37 % in NYHA II and 62 % in NYHA III , ejection fraction 0.31 , total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infa rct ion , 63 % hypertension , and 30 % diabetes . Patients are well treated for heart failure with 90 % on loop or thiazide diuretics , 42 % aldosterone antagonists , 91 % ACE inhibitor or AT-I blocker , 75 % beta-blockers , and 32 % digitalis . CONCLUSION CORONA is important for three main reasons : ( 1 ) A positive result is very important because of the high risk of the population studied , the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society , and the health economic issues involved . ( 2 ) If negative , new mechanistic questions about heart failure have to be raised . ( 3 ) If neutral we can avoid unnecessary polypharmacy Myocardial infa rct ion , sudden cardiac death , cerebrovascular accidents , blood pressure control and treatment tolerability were studied in a r and omized double-blind trial conducted in 6357 men and women aged 40 - 64 years with uncomplicated essential hypertension ( diastolic blood pressures 100 - 125 mmHg ) . At the start of the trial 3185 patients received treatment based on a beta-blocker ( oxprenolol )  , while in the remaining 3172 placebo replaced oxprenolol .  Supplementary drugs , excluding beta-blockers , were used as necessary in both treatment groups , with the aim of reducing diastolic pressure to 95 mmHg or less . Patients were followed for 3 - 5 years , a total of 25 651 patient years at risk . In most respects the two groups fared equally well ; sudden death ( relative risk [ RR ] 1.08 ; 95 % confidence interval [ Cl ] 0.68 and 1.72 ) , myocardial infa rct ion ( RR 0.83 ; Cl 0.59 and 1.16 ) and cerebrovascular accident ( RR 0.97 ; Cl 0.64 and 1.47 ) rates were similar . Beta-blocker based therapy was associated with significantly lower average blood pressures , earlier ECG normalization , less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension . Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability . In smokers the cardiac event rate was doubled . We propose that beta-blocker treatment effects depend on smoking status , with a significant interaction benefiting non-smoking men . Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events . Proportional hazards analysis also underlines the importance of other cardiovascular risk factors . The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients BACKGROUND Although r and omized clinical trials have demonstrated that beta-blocker therapy is effective in reducing mortality after acute myocardial infa rct ion ( AMI ) , many of these studies excluded patients who undergo coronary revascularization . However , the clinical practice guidelines established by the American College of Cardiology and the American Heart Association recommend that beta-blocker therapy be considered for patients who underwent successful revascularization after AMI . METHODS Using data from the Cooperative Cardiovascular Project , we compared the initiation of beta-blocker therapy at discharge in patients aged 65 years or older who underwent coronary artery bypass surgery ( CABG ) or percutaneous transluminal coronary angioplasty ( PTCA ) during their hospitalization for AMI with that of patients who did not undergo revascularization . We then examined whether beta-blocker therapy was associated with lower 1-year mortality between revascularized and nonrevascularized groups . RESULTS After excluding patients with contraindications to beta-blocker therapy , 84 457 patients remained in the study sample . Of these , 8482 patients underwent CABG , and 13 997 patients underwent PTCA . After adjusting for demographic and clinical factors , we found that these patients were less likely to initiate beta-blocker therapy after CABG ( odds ratio [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.41 - 0.47 ) or PTCA ( OR , 0.89 ; 95 % CI , 0.85 - 0.93 ) relative to the nonrevascularized group . After adjusting for potential confounders , beta-blockers were significantly associated with lower 1-year mortality in patients who underwent CABG ( hazard ratio [ HR ] , 0.70 ; 95 % CI , 0.55 - 0.89 ) or PTCA ( HR , 0.86 ; 95 % CI , 0.74 - 1.00 ) , similar to that of the non-revascularized group ( HR , 0.83 ; 95 % CI , 0.80 - 0.87 ) . CONCLUSIONS Therapy after AMI with beta-blockers appears to be as effective in reducing 1-year mortality for elderly patients who have undergone CABG or PTCA as for a nonrevascularized group . Our findings suggest that routine use of beta-blockers should be considered for patients who undergo revascularization after AMI
Atenolol  was the beta‐blocker most used .
Current evidence suggests that initiating treatment of hypertension with beta‐blockers leads to modest CVD reductions and little or no effects on mortality .
These beta‐blocker effects are inferior to those of other antihypertensive drugs .
Abstract Background Beta‐blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties .
They have shown long‐term beneficial effects on mortality and cardiovascular disease ( CVD ) when used in people with heart failure or acute myocardial infa rct ion .
Beta‐blockers were thought to have similar beneficial effects when used as first‐line therapy for hypertension .
However , the benefit of beta‐blockers as first‐line therapy for hypertension without compelling indications is controversial .
This review is an up date of a Cochrane Review initially published in 2007 and up date d in 2012 .
Objectives To assess the effects of beta‐blockers on morbidity and mortality endpoints in adults with hypertension .