***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT R and omized trials provide robust evidence for the impact of pharmacological and interventional treatments in patients with ST-segment elevation and non-ST-segment elevation acute coronary syndromes ( NSTE ACS ) , but whether this translates to changes in clinical practice is unknown . OBJECTIVE To determine whether changes in hospital management of patients with ST-segment elevation myocardial infa rct ion ( STEMI ) and NSTE ACS are associated with improvements in clinical outcome . DESIGN , SETTING , AND PATIENTS In the Global Registry of Acute Coronary Events ( GRACE ) , a multinational cohort study , 44 372 patients with an ACS were enrolled and followed up in 113 hospitals in 14 countries between July 1 , 1999 , and December 31 , 2006 . MAIN OUTCOME MEASURES Temporal trends in the use of evidence -based pharmacological and interventional therapies ; patient outcomes ( death , congestive heart failure , pulmonary edema , cardiogenic shock , stroke , myocardial infa rct ion ) . RESULTS Use of pharmacological medications increased over the study period ( beta-blockers , statins , angiotensin-converting enzyme inhibitors , thienopyridines with or without percutaneous coronary intervention [ PCI ] , glycoprotein IIb/IIIa inhibitors , low-molecular-weight heparin ; all P<.001 ) . Pharmacological reperfusion declined in patients with STEMI by -22 percentage points ( 95 % confidence interval [ CI ] , -27 to -17 ) , whereas primary PCI increased by 37 percentage points ( 95 % CI , 33 - 41 ) . In patients with non-STEMI , rates of PCI increased markedly by 18 percentage points ( 95 % CI , 15 - 20 ) . Rates of congestive heart failure and pulmonary edema declined in both population s : STEMI , -9 percentage points ( 95 % CI , -12 to -6 ) and NSTE ACS , -6.9 percentage points ( 95 % CI , -8.4 to -4.7 ) . In patients with STEMI , hospital deaths decreased by 18 percentage points ( 95 % CI , -5.3 to -1.9 ) and cardiogenic shock by -24 percentage points ( 95 % CI , -4.3 to -0.5 ) . Risk-adjusted hospital deaths declined -0.7 percentage points ( 95 % CI , -1.7 to 0.3 ) in NSTE ACS patients . Six-month follow-up rates declined among STEMI patients : stroke by -0.8 percentage points ( 95 % CI , -1.7 to 0.1 ) and myocardial infa rct ion by -2.8 percentage points ( 95 % CI , -6.4 to 0.9 ) . In NSTE ACS , 6-month death declined -1.6 percentage points ( 95 % CI , -3.0 to -0.1 ) and stroke by 0.7 percentage points ( 95 % CI , -1.4 to 0.1 ) . CONCLUSIONS In this multinational observational study , improvements in the management of patients with ACS were associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and mycoardial infa rct ion at 6 months The beta-Blocker Heart Attack Trial ( BHAT ) was a National Heart , Lung , and Blood Institute-sponsored , multicenter , r and omized , double-blind , and placebo-controlled trial design ed to test whether the regular administration of propranolol hydrochloride to men and women who had experienced at least one myocardial infa rct ion would result in a significant reduction in total mortality during a two- to four-year period . During a 27-month interval , 3,837 persons between the ages of 30 and 69 years were r and omized to either propranolol ( 1,916 persons ) or placebo ( 1,912 persons ) , five to 21 days after the infa rct ion . Depending on serum drug levels , the prescribed maintenance dose of propranolol hydrochloride was either 180 or 240 mg/day . The trial was stopped nine months ahead of schedule . Total mortality during the average 24-month follow-up period was 7.2 % in the propranolol group and 9.8 % in the placebo group . Arteriosclerotic heart disease ( ASHD ) mortality was 6.2 % in the propranolol group and 8.5 % in the placebo group . Sudden cardiac death , a subset of ASHD mortality , was 3.3 % among the propranolol patients and 4.6 % among the placebo patients . Serious side effects were uncommon . Hypotension , gastrointestinal problems , tiredness , bronchospasm , and cold h and s and feet occurred more frequently in the propranolol group . Based on the BHAT results , the use of propranolol in patients with no contraindications to beta-blockade who have had a recent myocardial infa rct ion is recommended for at least three years A multicenter double-blind r and omized study was carried out to compare the effect of timolol ( 10 mg twice daily ) with that of placebo in patients surviving acute myocardial infa rct ion . Treatment was started seven to 28 days after infa rct ion in 1884 patients ( 945 taking timolol , and 939 placebo ) , who represented 52 per cent of those evaluated for entry ; the patients were followed for 12 to 33 months ( mean , 17 ) . There were 152 deaths in the placebo group and 98 in the timolol group . When deaths that occurred during treatment or within 28 days of withdrawal were considered , the cumulated sudden-death rate over 33 months was 13.9 per cent in the placebo group and 7.7 per cent in the timolol group -- a reduction of 44.6 per cent ( P = 0.0001 ) . The cumulated reinfa rct ion rate was 20.1 per cent in the placebo group and 14.4 per cent in the timolol group ( P = 0.0006 ) . We conclude that long-term treatment with timolol in patients surviving acute myocardial infa rct ion reduces mortality and the rate of reinfa rct ion 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 ) 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 BACKGROUND Despite previous r and omised trials of early beta-blocker therapy in the emergency treatment of myocardial infa rct ion ( MI ) , uncertainty has persisted about the value of adding it to current st and ard interventions ( eg , aspirin and fibrinolytic therapy ) , and the balance of potential benefits and hazards is still unclear in high-risk patients . METHODS 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were r and omly allocated metoprolol  ( up to 15 mg intravenous then 200 mg oral daily ; n=22,929 ) or matching placebo ( n=22,923 ) . 93 % had ST-segment elevation or bundle branch block , and 7 % had ST-segment depression . Treatment was to continue until discharge or up to 4 weeks in hospital ( mean 15 days in survivors ) and 89 % completed it . The two prespecified co- primary outcomes were : ( 1 ) composite of death , reinfa rct ion , or cardiac arrest ; and ( 2 ) death from any cause during the scheduled treatment period . Comparisons were by intention to treat , and used the log-rank method . This study is registered with Clinical Trials.gov , number NCT 00222573 . FINDINGS Neither of the co- primary outcomes was significantly reduced by allocation to metoprolol . For death , reinfa rct ion , or cardiac arrest , 2166 ( 9.4 % ) patients allocated metoprolol had at least one such event compared with 2261 ( 9.9 % ) allocated placebo ( odds ratio [ OR ] 0.96 , 95 % CI 0.90 - 1.01 ; p=0.1 ) . For death alone , there were 1774 ( 7.7 % ) deaths in the metoprolol group versus 1797 ( 7.8 % ) in the placebo group ( OR 0.99 , 0.92 - 1.05 ; p=0.69 ) . Allocation to metoprolol was associated with five fewer people having reinfa rct ion ( 464 [ 2.0 % ] metoprolol vs 568 [ 2.5 % ] placebo ; OR 0.82 , 0.72 - 0.92 ; p=0.001 ) and five fewer having ventricular fibrillation ( 581 [ 2.5 % ] vs 698 [ 3.0 % ] ; OR 0.83 , 0.75 - 0.93 ; p=0.001 ) per 1000 treated . Overall , these reductions were 
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Also , small study effect was demonstrated by a cumulative meta- analysis starting with the largest study showing no effect , with increasing effect as the smaller studies were accumulated .
Conclusion Evidence from this study suggests that there is no association  between β-blockers and all-cause mortality .