ß-Blockers and Progression of Coronary Atherosclerosis

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

Ilke Sipahi, MD; E. Murat Tuzcu, MD; Katherine E. Wolski, MPH; Stephen J. Nicholls, MBBS, PhD; Paul Schoenhagen, MD; Bo Hu, PhD; Craig Balog, BS; Mehdi Shishehbor, DO; William A. Magyar, BS; Timothy D. Crowe, BS; Samir Kapadia, MD; and Steven E. Nissen, MD

3 July 2007 Volume 147 Issue 1 Pages 10-18

Background: In patients with myocardial infarction, ß-adrenergic blockers reduce recurrent myocardial infarction and total mortality rates. However, whether a direct influence of ß-blockers on coronary atherosclerosis contributes to reduced recurrent myocardial infarction and total mortality rates is not known.

Objective: To assess whether ß-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 ß-blocker treatment.

Results: Patients who received ß-blockers (n = 1154) were more likely to have histories of myocardial infarction, angina, and hypertension than were patients who did not receive ß-blockers (n = 361). The estimated annual change in atheroma volume was statistically significantly less in patients who received ß-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 ß-blockers (P < 0.001) and did not change in patients who did not receive ß-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 ß-blocker therapy, and interventions other than ß-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 ß-blockers can slow progression of coronary atherosclerosis. The findings provide additional support for the current clinical guidelines advocating long-term use of ß-blockers to treat most forms of coronary artery disease.


Editors' Notes

Context
The mechanisms by which ß-blockers prevent recurrent myocardial infarction are not clear.

Contribution
This pooled analysis of individual patient data examines changes in coronary atheroma volume as measured by serial intravascular ultrasonography in 4 randomized trials. The trials followed 1515 patients with coronary artery disease for 18 to 24 months. Atheroma volume decreased in patients who were receiving ß-blockers but stayed the same in those not receiving ß-blockers.

Cautions
The trials tested other interventions (such as statins) that could have affected atheromas. We do not know whether changes in atheroma volume predict cardiovascular outcomes.

Implication
ß-Blockers probably slow progression of coronary atherosclerosis.