β-Blockers and Progression of Coronary Atherosclerosis: Pooled Analysis of 4 Intravascular Ultrasonography Trials

BACKGROUND: In patients with myocardial infarction, beta-adrenergic blockers reduce recurrent myocardial infarction and total mortality rates. However, whether a direct influence of beta-blockers on coronary atherosclerosis contributes to reduced recurrent myocardial infarction and total mortality rates is not known. OBJECTIVE: To assess whether beta-blocker therapy is associated with reduced atheroma progression in adults with known coronary artery disease. DESIGN: Post hoc, pooled analysis of individual patient data from 4 intravascular ultrasonography (IVUS) trials. SETTING: Four IVUS trials conducted in the United States, Europe, and Australia. PATIENTS: 1515 patients with coronary artery disease. INTERVENTION: The original trials used 3 different statins, a calcium-channel blocker, an angiotensin-converting enzyme inhibitor, or an acyl coenzyme A-cholesterol acyltransferase inhibitor. MEASUREMENTS: Changes in atheroma volume, as determined by IVUS after adjustment for possible confounders by using linear mixed-effects models, were compared in patients who did and did not receive concomitant beta-blocker treatment. RESULTS: Patients who received beta-blockers (n = 1154) were more likely to have histories of myocardial infarction, angina, and hypertension than were patients who did not receive beta-blockers (n = 361). The estimated annual change in atheroma volume was statistically significantly less in patients who received beta-blockers. This was true for univariate and multivariable analyses that controlled for history of myocardial infarction, angina, and hypertension (mean [+/-SE] atheroma volume, -2.4 +/- 0.5 mm3/y in treated patients vs. -0.4 +/- 0.8 mm3/y in untreated patients; P = 0.034). Accordingly, atheroma volume statistically significantly decreased at follow-up IVUS in patients who received beta-blockers (P < 0.001) and did not change in patients who did not receive beta-blockers (P = 0.86). Additional adjustments for low-density lipoprotein cholesterol level, concomitant medications, and clinical trial did not change the results. LIMITATIONS: Patients were not randomly assigned to beta-blocker therapy, and interventions other than beta-blocker therapy could have influenced the changes in atheroma volume. Whether progression rate of atherosclerosis as detected by IVUS predicts cardiovascular outcomes is unknown. CONCLUSIONS: The analysis demonstrates that beta-blockers can slow progression of coronary atherosclerosis. The findings provide additional support for the current clinical guidelines advocating long-term use of beta-blockers to treat most forms of coronary artery disease.