Beta-Blockers After Acute MI

Study Questions:

What is the association of beta-blocker dose with survival after acute myocardial infarction (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:

0f 6,682 with follow-up (median 2.1 years), 91.5% were discharged on beta-blocker (mean dose 38.1%). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios (HRs) for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI], 0.677-1.098), 0.799 (95% CI, 0.635-1.005), and 0.963 (95% CI, 0.765-1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose, 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:

The authors concluded that data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in prior randomized clinical trials compared with lower doses.

Perspective:

This registry study reports no improvement in outcomes with higher-dose beta-blocker therapy, more specifically the target beta-blocker doses used in prior randomized clinical trials. While baseline differences in the treatment groups prevent a definitive determination of the dose-response relationship between beta-blocker dose and mortality post-MI, the lowest observed mortality was at 25% of the target dose used in randomized trials (i.e., metoprolol 50 mg/day). These findings suggest the need to re-engage in research to establish appropriate beta-blocker dosing following MI to derive optimal benefit.

Clinical Topics: Acute Coronary Syndromes, Prevention

Keywords: Acute Coronary Syndrome, Adrenergic beta-Antagonists, Metoprolol, Myocardial Infarction, Primary Prevention, Survival


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