One-Year Landmark Analysis of the Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction

Abstract

Background Although beta-blockers are recommended following myocardial infarction (MI), the benefits of long-term treatment have not been established. The study's aim was to evaluate beta-blocker efficacy by dose in 1-year post-MI survivors. Methods and Results The OBTAIN (Outcomes of Beta-Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one-year survivors. For this landmark analysis, beta-blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta-blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow-up duration was 1.05 years (interquartile range, 0.98-1.22). When analyzed dichotomously, beta-blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no-beta-blocker group (hazard ratio,1.997; 95% CI, 1.118-3.568; P<0.02), the >0% to 12.5% group (hazard ratio, 1.817; 95% CI, 1.094-3.016; P<0.02), and the >25% to 50% group (hazard ratio, 1.764; 95% CI, 1.105-2.815; P<0.02), compared with the >12.5% to 25% dose group. The mortality in the full-dose group was not significantly higher (hazard ratio, 1.196; 95% CI, 0.687-2.083). In subgroup analyses, only history of congestive heart failure demonstrated significant interaction with beta-blocker effects on survival. Conclusions This analysis suggests that patients treated with >12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta-blocker and other beta-blocker doses. A new paradigm for post-MI beta-blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose.

Keywords: beta‐blocker; landmark analysis; myocardial infarction; survival.

Figure 1. Histogram of change in beta‐blocker (BB) dosing from discharge to 1 year.

Figure 2. Kaplan‐Meier survival curves with landmark analysis from 1 year after myocardial infarction (MI) based on beta‐blocker (BB) dose at 1 year.

The top (>12.5%–25%) and bottom (>25–50%) survival curves are labeled. The legend provides the doses for the overlapping blue, red, and purple curves.

Figure 3. Hazard ratios for the multivariable and propensity score analyses for the various beta‐blocker (BB) groups relative to the >12.5% to 25% dose.

*P<0.08 versus >12.5% to 25% dose. ^† P<0.02 versus >12.5% to 25% dose.