β-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction

Background For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. Objectives The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Methods This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Results Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Conclusions Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)

H istorically, b-blockers have been the standard of care for patients with acute myocardial infarction (AMI). However, clinical uncertainty exists regarding their effectiveness in reducing mortality among patients with AMI who do not have heart failure (HF) or left ventricular systolic dysfunction (LVSD). For example, although there is sufficient evidence to support the use of b-blockers in patients with AMI and HF (1,2), as well as in hospitalized patients who are hemodynamically stable (3,4), there are no contemporary randomized data for survivors of AMI without HF or LVSD in relation to the use of b-blockers. As such, international guidelines differ in their recommendation regarding the use of b-blockers after AMI (5)(6)(7)(8).
Results from recent observational studies suggest no significant association between the use of b-blockers among patients with AMI who do not have HF or LVSD and clinical outcomes. A meta-analysis comprising 16,645 patients with preserved left ventricular ejection fraction and who received percutaneous coronary intervention (PCI) for AMI found that the use of b-blockers was not associated with improved survival (9). However, recent data for 2,679 patients with AMI without HF or LVSD recorded in the FAST-MI (French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction) study found that early b-blocker use was associated with reduced 30-day mortality, but their discontinuation at 1 year was not associated with higher 5-year mortality (10).
To the best of our knowledge, to date, there are no analyses of large-scale datasets that have investigated the impact of b-blockers on survival after AMI among patients without HF or LVSD. On one hand, discontinuing b-blockers in survivors of AMI who do not have HF may prevent unnecessary overtreatment and costs, and improve adherence to other medications. On the other hand, randomized evidence to date suggests that use of b-blockers after AMI reduces clinical events (3,11). The goal of the present study, therefore, was to use the United Kingdom national heart attack register, known as MINAP   For the present study, HF was defined as a history of HF, use of a loop diuretic on or during hospitalization, and/or a left ventricular ejection fraction <30% as recorded in the hospital. b-blocker use was determined according to whether eligible patients had received b-blockers at discharge from the hospital.
The primary outcome was all-cause mortality at 1 year after hospitalization. STATISTICAL ANALYSIS. Baseline characteristics according to treatment with b-blockers were described by using number and percentage for categorical data and mean AE SD or median and interquartile range for normally and non-normally distributed continuous data, respectively. Differences in characteristics were assessed by using chi-square tests, 2-sample Student t tests, and, for non-normally distributed data, the Mann-Whitney U test. Adjusted Kaplan-Meier curves were used to assess survival differences between patients who received b-blockers and those who did not.
Survival time inverse probability weighting propensity score analysis (13,14) was used to evaluate the association between b-blocker use and mortality by estimating the average treatment effects (ATEs) and ATEs on the treated. Briefly, the method incorporated 2 models, the first of which was a treatment assignment model that estimated the propensity for b-blocker treatment assignment and was used to derive inverse probability weights.     There was also no significant treatment effect for the use of b-blockers at 1 month, 6 months, and 1 year for STEMI and NSTEMI.     (19).
A meta-analysis of 10 observational studies across >40,000 patients suggested a lack of evidence to support the routine use of b-blockers in all patients with AMI who received PCI, but the effect was restricted to those with a reduced ejection fraction, NSTEMI, and those with low use of secondary prevention medications (9). Moreover, while b-blockers have been shown to be beneficial if given early after STEMI in patients who are hemodynamically stable, this effect is largely driven by a reduction in ventricular arrhythmias and reinfarction, and it was not known if there was a mortality advantage after 1 month of use among patients with STEMI or NSTEMI and who did not have HF or a preserved ejection fraction (4).
No randomized trials have tested the efficacy of b-blockers on long-term mortality among patients with AMI without HF or LVSD. Until now, the largest study, which comprised 6,758 propensity scorematched patients with AMI, found no reduction in mortality according to use of b-blockers (20). Notably, this study censored data in 2009 and did not investigate the impact of b-blockers on mortality among patients without HF or according to diagnosis of STEMI and NSTEMI. A smaller, but more recent study found that the discontinuation of b-blockers at 1 year was not associated with higher 5-year mortality (10). This finding is important because guidelines recommend that b-blockers be prescribed long term for patients after AMI who have HF, and it is uncertain as to whether b-blockers are beneficial for patients without HF but who have presented to the hospital with STEMI or NSTEMI.
In an era of coronary revascularization for AMI, whether it is primary PCI for acute STEMI or a risk-dependent early invasive strategy for NSTEMI, the likelihood of preserving more viable and therefore less arrhythmogenic myocardium is potentially greater than that of the noninterventional era.   (16,17). In such circumstances, there is good evidence that b-blockers are beneficial and associated with lower mortality rates and better cardiovascular outcomes (22).
In addition, there was no information in the present study about rates of discontinuation, new prescriptions, or doses of b-blockers after hospital discharge. It is possible that nonpersistence with (ATET) represent the absolute difference in survival time between b-blocker treatment versus no b-blocker treatment estimated only among those who were treated (comparing survival times for all b-blocker patients versus the potential survival time in the scenario that the treated patients did not receive b-blockers).
AMI ¼ acute myocardial infarction; CI ¼ confidence interval; other abbreviations as in Table 1. Abbreviations as in Tables 1 and 2. In this study, patients experiencing an acute myocardial infarction (AMI) without heart failure (HF) or left ventricular systolic dysfunction were commonly prescribed b-blockers at hospital discharge (94.8%). However, in this nationwide observational study using propensity score analysis (1-year follow-up), the use of b-blockers was not associated with a significant difference in survival times after AMI.