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

Background-The long-term efficacy of beta-blockers in patients with and without myocardial infarction (MI) is controversial. Methods and Results-This is post hoc analysis from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial of 4772 patients with prior MI, 7804 patients with known atherothrombosis, and 2101 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 2 groups based on baseline beta-blocker use. 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%] versus 100 [10.2%]; hazards ratio, 0.69; 95% confidence interval, 0.50-0.94; P= 0.021), driven by a lower risk of recurrent MI (33 [3.4%] versus 48 [4.9%]; hazards ratio, 0.62; 95% confidence interval, 0.39-1.00; P= 0.049) with no difference in mortality (52 [5.3%] versus 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% versus 1.5%; hazards ratio, 2.13; 95% confidence interval, 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 (hazards ratio, 2.69; 95% confidence interval, 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 risk of 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.