Abstract 4140452: Impact of Beta-Blocker Dosage on All-Cause Mortality Post-Myocardial Infarction in Patients with Ejection Fraction ≥50%

Background: The recent REDUCE-AMI trial showed no benefit to beta-blockers (BB) for patients post-myocardial infarction (MI) with preserved ejection fraction (EF≥50%). Target doses were metoprolol 100 mg and bisoprolol 5 mg daily (50% of the target doses used in the initial randomized clinical trials [RCTs] of BB post-MI). Research question: Do lower BB doses improve survival in post-MI patients with EF≥50%? Aims: To compare the effect of BB dose on all-cause mortality post-MI in patients with EF≥50%. Methods: This is a sub-study from the OBTAIN prospective multi-center registry. Of 7057 patients enrolled with acute MI, 3402 with EF≥50% were discharged alive (age:62.5±13.4 years, 67% male, 28% diabetics, length of stay 6.1±6.0 days). Discharge BB dose was indexed to the target daily BB dose used in RCTs, reported as %. Dosage groups were >0-12.5%, >12.5-25%, >25-50%, and >50% of the target dose. Follow-up vital status was obtained by chart review, Social Security Death Index, or direct contact up to 3 years post-MI. Kaplan-Meier (KM) method was used to calculate three-year survival. Cox proportional hazard regression model was used to identify significant predictors and conduct univariate and multivariate analysis. Results: The KM 3 year survival estimates were 89.0% and 84.3% for patients on and off BB, respectively (unadjusted hazard ratio (HR)=0.66, p=0.012; adjusted HR=0.52, p=0.18). The KM 3 year survival estimates(figure) were 89.8%, 91.0%, 87.9%, and 83.1% for patients on >0-12.5%, >12.5-25%, >25- 50%, and >50% of the BB target dose (unadjusted HR of 0.58, p=0.007; 0.58, p=0.003; 0.70; p=0.066; and 0.98, p=0.93), respectively, compared to no BB. After multivariate analysis, BB target dose showed similar trend, but not statistically significant (adjusted HR=0.65, p=0.46; 0.42, p=0.13; 0.53, p=0.31; 1.01, p=0.92). Conclusion: In OBTAIN, patients treated with low dose BB (≤25% of the target dose) had improved survival post-MI. As this dose was not studied in REDUCE-AMI, these findings are complementary and confirm only that high dose BB therapy provides no benefit post-MI in patients with preserved EF. RCTs to assess the benefit of low dose BB therapy post-MI with preserved EF are needed.