Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events? A Meta-Analysis of 41 Randomized Trials

Objectives The purpose of this study was to verify whether intima-media thickness (IMT) regression is associated with reduced incidence of cardiovascular events. Background Carotid IMT increase is associated with a raised risk of coronary heart disease (CHD) and cerebrovascular (CBV) events. However, it is undetermined whether favorable changes of IMT reflect prognostic benefits. Methods The MEDLINE database and the Cochrane Database were searched for articles published until August 2009. All randomized trials assessing carotid IMT at baseline, at end of follow-up, and reporting clinical end points were included. A weighted random-effects meta-regression analysis was performed to test the relationship between mean and maximum IMT changes and outcomes. The influence of baseline patients' characteristics, cardiovascular risk profile, IMT at baseline, follow-up, and quality of the trials was also explored. Overall estimates of effect were calculated with a fixed-effects model, random-effects model, or Peto method. Results Forty-one trials enrolling 18,307 participants were included. Despite significant reduction in CHD, CBV events, and all-cause death induced by active treatments (for CHD events, odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.69 to 0.96, p = 0.02; for CBV events, OR: 0.71, 95% CI: 0.51 to 1.00, p = 0.05; and for all-cause death, OR: 0.71, 95% CI: 0.53 to 0.96, p = 0.03), there was no significant relationship between IMT regression and CHD events (Tau 0.91, p = 0.37), CBV events (Tau -0.32, p = 0.75), and all-cause death (Tau-0.41, p = 0.69). In addition, subjects' baseline characteristics, cardiovascular risk profile, IMT at baseline, follow-up, and quality of the trials did not significantly influence the association between IMT changes and clinical out-comes. Conclusions Regression or slowed progression of carotid IMT, induced by cardiovascular drug therapies, do not reflect reduction in cardiovascular events. (J Am Coll Cardiol 2010;56:2006-20) (C) 2010 by the American College of Cardiology Foundation