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

https://doi.org/10.1016/j.jacc.2015.07.047Get rights and content
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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)

Key Words

adrenergic beta-antagonists
follow-up studies
registries
survival analysis

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
CI
confidence interval
HR
hazard ratio
MI
myocardial infarction

Cited by (0)

This research was supported by grant 5U01HL080416 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The views expressed in this manuscript are the authors' and do not necessarily reflect those of the National Institutes of Health or the Department of Health and Human Services. Dr. Liu is a consultant to Celladon, Outcome Research Solutions, and Zensun. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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