β-Blockers and Cardiovascular Events in Patients With and Without Myocardial Infarction: Post Hoc Analysis From the CHARISMA Trial

Study Questions:

What is the long-term efficacy of beta-blockers in patients with and without myocardial infarction (MI)?

Methods:

A post hoc analysis was conducted in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial of 4,772 patients with prior MI, 7,804 patients with known atherothrombosis, and 2,101 patients with risk factors alone, but without heart failure. Primary outcome was a composite of nonfatal MI, stroke, or cardiovascular mortality. The cohorts were divided into two groups based on baseline beta-blocker use.

Results:

In the propensity score–matched prior MI cohort, after 28 months of follow-up, beta-blocker use was associated with a 31% lower risk of the primary outcome (70 [7.1%] vs. 100 [10.2%]; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.50-0.94; p = 0.021), driven by a lower recurrent MI (33 [3.4%] vs. 48 [4.9%]; HR, 0.62; 95% CI, 0.39-1.00; p = 0.049) with no difference in mortality (52 [5.3%] vs. 66 [6.7%]; p = 0.20). In the known atherothrombotic disease and the risk factors alone cohorts, beta-blocker use was not associated with lower ischemic outcomes, whereas a trend toward a higher risk of stroke (3.5% vs. 1.5%; HR, 2.13; 95% CI, 0.92-4.92; p = 0.079) was observed in the risk factors alone cohort. This higher stroke risk was significant in the regression model adjusted to the propensity score (HR, 2.69; 95% CI, 1.33-5.44; p = 0.006) and in the multivariable models.

Conclusions:

Beta-blocker use in patients with prior MI, but no heart failure was associated with a lower composite cardiovascular outcome driven by lower recurrent MI with no difference in mortality. However, beta-blocker use was not associated with lower cardiovascular events in those without MI, with a suggestion of inferior outcome with regard to stroke risk.

Perspective:

The same authors published a meta-analysis in 2014 (Am J Med) and found that other than short-term (30 days) reduction in angina and recurrent MI, there was no value of beta-blockers in the reperfusion era. The findings in CHARISMA are very similar to the very large REACH clinical registry. It is important that the guidelines (post-MI, acute coronary syndrome, stable coronary artery disease), and those at high risk, properly reflect the risk/benefit of beta-blockers in the modern era; particularly considering how long it takes to change clinical practice and how guideline compliance is used to rate standards of care by physicians and hospitals.

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Follow-Up Studies, Propensity Score, Adrenergic beta-Antagonists, Risk Factors, Ticlopidine


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