Beta blockers after heart attack even with preserved LV function: still unclear

For many years, beta-blocker treatment after myocardial infarction has routinely been initiated in almost all patients despite the lack of evidence supporting its use in the context of contemporary treatment of myocardial infarction. While this evidence is now available for patients with impaired LV function, the data for patients with a left ventricular ejection fraction (LVEF) of ≥40% was sparse: Previously conducted trials such as CAPITAL RCT and REDUCE-AMI were not able to demonstrate any outcome benefit of beta-blocker therapy for these patients.

The results of two large randomized studies and a parallel meta-analysis were recently presented at the ESC congress, which attempted to answer the question whether beta-blocker therapy is beneficial in patients with an myocardial infarction and preserved/moderately reduced ejection fraction.

In the BETAMI-DANBLOCK study, 5,574 patients after acute myocardial infarction with an LVEF ≥ 40% were randomized to beta-blocker therapy (95% metoprolol) or no beta-blocker therapy. Beta-blocker therapy had to be started no later than 14 days after the acute event. After a median follow-up of 3.5 years, the primary endpoint consisting of death, recurrent myocardial infarction, unplanned revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias occurred in 14.2 % of the treatment group and 16.3% of the control group (HR 0.85; 95% CI [0.75; 0.98], p=0.03). No significant differences were found between the groups with regard to the individual components of the primary endpoint.

The REBOOT-CNIC study randomized 8,505 patients after acute myocardial infarction with an LVEF >40% and selected a composite endpoint consisting of death, myocardial infarction, and heart failure as the primary endpoint. After a follow-up period of approximately 4 years, there was no difference in the primary endpoint between the groups (beta blocker: 22.5 events/1000 patient-years vs. no beta blocker: 21.7 events/1000 patient-years; HR 1.04, 95% CI [0.89; 1.22], p=0.63).

The combined results of these studies suggest that not all post-infarction patients benefit from beta-blocker therapy, but that those with mildly reduced LVEF may derive a protective effect. This finding is supported by a subsequent meta-analysis of the named studies: in n=1,885 patients with an LVEF of 40% to <50% from the BETAMI-DANBLOCK, REBOOT-CNIC, and CAPITAL trials, a beneficial effect of a beta-blocker therapy on the composite endpoint of death, myocardial infarction, and heart failure (32.6 events/1000 patient-years vs. 43.0 events per 1000 patient-years, HR 0.75; 95% CI (0.58; 0.97), p=0.031) was noted.

In summary, current evidence suggests that routine beta-blocker therapy might not be indicated for all post-infarction patient with an LVEF of >40%, as the majority of available RCTs fail to demonstrate a meaningful outcome benefit in these individuals. The sole trial reporting a positive effect, BETAMI-DANBLOCK, demonstrated only a modest absolute difference between treatment groups and was based on a relatively soft composite endpoint. However, subgroup analyses and a supporting meta-analysis indicate that patients with moderately impaired LV function may still benefit from beta-blocker therapy. This subgroup warrants separate evaluation in future studies until more definitive conclusions can be drawn.

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