Are changes in carotid intima-media thickness related to risk of nonfatal myocardial infarction? A critical review and meta-regression analysis

Background Carotid intima-media thickness (CIMT) is increasingly being used as a surrogate end point in randomized control trials (RCTs) of novel cardiovascular therapies. However, it remains unclear whether changes in CIMT that result from these therapies correlate with nonfatal myocardial infarction (MI). Methods We performed a literature search of RCTs from 1990-2009 that used CIMT. Eligible RCTs (1) included quantitative and sequential assessments in CIMT at least 1 year apart and (2) reported nonfatal MI. Across RCTs, random-effects metaregression was employed to correlate differences in mean change in CIMT between treatment and control groups over time with the log odds ratios of developing nonfatal MI during follow-up. Results Overall, we identified 28 RCTs with 15,598 patients. Differences in mean change in CIMT over time between treatment and control groups correlated with developing nonfatal MI during follow-up: for each 0.01 mm per year smaller rate of change in CIMT, the odds ratio for MI was 0.82 (95% CI, 0.69 to 0.96; P = .018). Results were similar in subgroups of RCTs with >1 year follow-up (P = .018) and those with at least 50 subjects in the treatment group (P = .019). However, there was no significant relationship between mean change in CIMT and nonfatal MI in RCTs evaluating statin therapy or those with high CIMTs at baseline (P > .20 in both instances). Conclusions Less progression in CIMT over time is associated with a lower likelihood of nonfatal MI in selected RCTs; however, these findings were inconsistent at times, suggesting caution in using CIMT as a surrogate end point. (Am Heart J 2010; 160: 701-14.)