How well do drugs reverse atherosclerosis?

May 21, 2007

Three trials at this year's ACC meeting in New Orleans focused on pharmacotherapy effects on cardiovascular disease, one with a strong showing for medical therapy alone versus mechanical intervention.

Key Points

Adding a percutaneous coronary intervention (PCI), usually stenting, to optimal medical therapy (OMT) in patients with stable coronary artery disease (CAD) did not reduce the risk of death, myocardial infarction (MI), or other major cardiovascular events in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial. William E. Boden, M.D., professor of medicine and public health at the University at Buffalo School of Medicine and Biomedical Sciences, noted that among the more than one million PCIs performed annually in the country, the great majority are electively performed in patients with stable CAD. While it might be expected that successful PCI would reduce death, MI, or hospitalizations in these acute coronary syndrome (ACS) patients, research has confirmed only decreases in angina frequency and short-term exercise performance.

COURAGE was conducted at 50 North American hospitals among 2,287 patients randomized to PCI+OMT or OMT alone. Intensive, guideline-driven OMT and lifestyle intervention were given in both groups. Risk factor reduction goals focused on smoking, dietary fat, dietary and serum cholesterol, physical activity, body mass index, blood pressure, and diabetes. Follow-up was two and a half to seven years. The primary outcome was death or nonfatal MI.

William S. Weintraub, M.D., Emory University, who conducted COURAGE health status and economic substudies, said PCI+OMT incrementally improved angina compared with OMT alone. "But failing to reduce death or MI, PCI plus OMT as a first choice for stable CAD is expensive," he said. Investigators noted that these findings do not impact PCI use in unstable ACS patients.

METEOR trial

In the METEOR (Measuring Effects on Intima Media Thickness: An Evaluation of Rosuvastatin) trial in low-risk asymptomatic CAD subjects with early signs of atherosclerosis, rosuvastatin slowed and virtually halted progression of carotid plaques during two years of treatment. Professor of medicine John R. Crouse III, M.D., Wake Forest University School of Medicine, noted that carotid artery intima media thickness (CIMT) is a reliable marker of atherosclerotic burden and predictor of future cardiovascular events. METEOR tested whether greater LDL-cholesterol (LDL-C) reductions with more intensive statin therapy would pro-duce greater effects. The trial asked whether rosuvastatin (Crestor, AstraZeneca) therapy could slow progression of CIMT compared with placebo and/or induce regression of CIMT in all sites of the carotid artery.

METEOR randomized subjects from 61 U.S. and European centers to rosuvastatin 40 mg or placebo, assessing CIMT with ultrasound. Included individuals had LDL-C ≥120 to <190 mg/dl with no coronary heart disease risk factor other than age, or LDL-C ≥ 120 to <160 mg/dl with more than one risk factor, triglycerides <500 mg/ dl, and maximum CIMT of at least 1.2 mm at any site and less than 3.5 mm in all sites. This low-risk population was chosen in order to allow a placebo comparison, Crouse said. The primary endpoint was rate of change (mm/yr) in maximum CIMT based on all carotid measurements.