Phase 4 beta-blocker trial does not meet primary endpoint in post-MI patients with preserved LVEF
ACC.24 - In the REDUCE-AMI trial, long-term beta-blocker treatment did not lower the risk of all-cause mortality or new MI in patients with acute MI and LVEF ≥50% compared with no beta-blocker therapy.
This summary is based on the presentation of Troels Yndigegn, MD (Lund, Sweden) at the ACC.24 Scientific Session - Long-term Beta-blocker Treatment After Acute Myocardial Infarction And Preserved Left Ventricular Ejection Fraction – The REDUCE-AMI Trial.
Introduction and methods
Most trials showing benefit of beta-blocker treatment after MI included patients with large MIs and LV systolic dysfunction. In addition, these trials were primarily conducted in the 1980s, when there were no modern biomarker-based MI diagnostic options or reperfusion treatments. Contemporary clinical trials on the effect of long-term beta-blocker therapy in patients with an acute MI and preserved LVEF are lacking.
The REDUCE-AMI (Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction) trial was an international, multicenter, registry-based, parallel-group, open-label, event-driven, phase 4 RCT in which 5020 patients with an acute MI and LVEF ≥50% who had undergone coronary angiography were randomized to long-term treatment with an oral beta-blocker (metoprolol (first choice) or bisoprolol (alternative)) or no beta-blocker therapy, in addition to standard care. Median follow-up time was 3.5 years (IQR: 2.2–4.7).
The primary endpoint was a composite outcome of all-cause mortality or new nonfatal MI. Secondary endpoints included all-cause mortality, CV death, new MI, and hospitalization for HF or AF. Safety endpoints were hospitalization for bradycardia, AV block II–III, hypotension, syncope, or implantation of a pacemaker; hospitalization for asthma or COPD; and hospitalization for stroke.
Main results
- There was no difference in the incidence rate of the primary endpoint between patients treated with beta-blockers (n=2508) and those not receiving beta-blockers (n=2512) (7.9% vs. 8.3%; HR: 0.96; 95%CI: 0.79–1.16; P=0.64).
- With regard to the secondary endpoints, beta-blocker treatment did not reduce the cumulative incidence of all-cause mortality (3.9% vs. 4.1%; HR: 0.94; 95%CI: 0.71–1.24), CV death (1.5% vs. 1.3%; HR: 1.15; 95%CI: 0.72–1.84), MI (4.5% vs. 4.7%; HR: 0.96; 95%CI: 0.74–1.24), hospitalization for AF (1.1% vs. 1.4%; HR: 0.79; 95%CI: 0.48–1.31), and hospitalization for HF (0.8% vs. 0.9%; HR: 0.91; 95%CI: 0.50–1.66) compared with no beta-blocker therapy.
- The incidence rates of the safety endpoints also did not differ between the beta-blocker and no–betablocker groups (HR for hospitalization for bradycardia, AV block II–III, hypotension, syncope, or implantation of a pacemaker: 1.08; 95%CI: 0.79–1.46; HR for asthma or COPD: 0.94; 95%CI: 0.46–1.89; HR for hospitalization for stroke: 6.80; 95%CI: –7.11 to 20.72).
Conclusion
In the phase 4 REDUCE-AMI trial, long-term beta-blocker treatment did not lower the risk of the composite primary endpoint of all-cause mortality or new MI in patients with acute MI who underwent early coronary angiography and had a preserved LVEF, compared with no beta-blocker therapy. Beta-blocker therapy also did not appear to have an effect on any of the secondary endpoints, including CV death and hospitalization for HF or AF, and safety endpoints.
Dr. Yndigegn remarked that the event rate was very low, meaning that the study population was a low-risk group. Still, “in light of these findings, the REDUCE-AMI challenges the routine prescription of beta-blockers for MI patients with preserved ejection fraction, [which provides] an opportunity to tailor treatment to individual patient profiles.”
- Our reporting is based on the information provided at the ACC.24 Scientific Session -