Results From a Carotid Intima-Media Thickness Trial as a Decision Tool for Launching a Large-Scale Morbidity and Mortality Trial

Background-Trials with carotid intima-media thickness (CIMT) as primary end point may improve the efficiency of the evaluation of new therapies targeting atherosclerosis considerably, and the results of CIMT trials may be used as a decision tool to help in the choice to launch or not to launch a large-scale morbidity and mortality (M&M) trial. We evaluated the literature to provide evidence to support or refute this proposition.

Methods and Results-PubMed Medline was systematically searched on May 1, 2012, for randomized double-blind controlled CIMT trials. The agreement between the results from CIMT and M&M trials was assessed, and positive and negative predictive values were calculated. Forty-eight CIMT trials were included. CIMT trials (n=20) on lipid-level modifying therapies are all, except one, in agreement with the M&M trial findings. For blood pressure-lowering trials (n=13), 3 were not congruent with the M&M trial. The positive and negative predictive value (95% confidence interval) of a CIMT trial to predict the outcome of a M&M trial are 96% (80-99%) and 83% (64-93%), respectively. The predictive values are higher for lipid-level modifying therapies than for other therapies.

Conclusions-A CIMT trial positioned before an M&M trial may considerably improve the efficiency of the evaluation of new drug therapies on atherosclerosis and cardiovascular disease risk. Hence, the results of a CIMT trial should be seen as a decision tool to support or refute the start of a large-scale M&M trial on drugs targeting atherosclerosis.