Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction

Abstract

Background: Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized 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 randomized 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 randomized 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 Infarction [OBTAIN]: NCT00430612).

Keywords: adrenergic beta-antagonists; follow-up studies; registries; survival analysis.

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Adjusted Hazard Ratios for 3-Year Survival With Multivariable Analyses and Propensity Score Analysis Relative to the >12.5–25% of Target Dose Group

Adjusted hazard ratios for 3-year survival with multivariable analysis incorporating the pre-specified variable set, multivariable analysis incorporating the expanded variable set, and propensity score analysis comparing mortality with each beta-blocker dose to the mortality observed in the >12.5% to 25% of the target dose group.* p

Central Illustration. Beta-blockers After MI: Unadjusted Kaplan-Meier Survival Curves for the 5 Discharge Doses Analyzed and Low and High Dose Beta-Blocker Therapy

Kaplan-Meier survival curves for (A) the primary (unadjusted) analysis comparing the 5 discharge doses (no beta-blocker [BB] and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the target dose) of beta-blockers and (B) the secondary (unadjusted) analysis comparing low-dose (≤25% of the target dose) to high-dose (≥50% of the target dose) beta-blocker therapy.