title: Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors.
abstract: BACKGROUND: Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT) of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins). METHODS AND RESULTS: We examine two separate systems of criteria that have been proposed to define surrogate endpoints, based on clinical and statistical arguments. We use published results and a formal meta-analysis to evaluate whether progression of carotid IMT meets these criteria for HMG-CoA reductase inhibitors (statins).IMT meets clinical-based criteria to serve as a surrogate endpoint for cardiovascular events in statin trials, based on relative efficiency, linkage to endpoints, and congruency of effects. Results from a meta-analysis and post-trial follow-up from a single published study suggest that IMT meets established statistical criteria by accounting for intervention effects in regression models. CONCLUSION: Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents.
authors.affiliation: Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. mespelan@wfubmc.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Espeland
authors.forename: Daniel H
authors.initials: DH
authors.lastname: O'leary
authors.forename: James G
authors.initials: JG
authors.lastname: Terry
authors.forename: Timothy
authors.initials: T
authors.lastname: Morgan
authors.forename: Greg
authors.initials: G
authors.lastname: Evans
authors.forename: Harald
authors.initials: H
authors.lastname: Mudra