The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial

Aims: To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS). Methods and results: In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0mg/dL with simvastatin/ezetimibe vs. 69.9mg/dL with simvastatin/placebo in patients with prior CABG (P < 0.001), and it was 53.6mg/dL vs. 69.5 mg/dL, respectively, in patients without prior CABG (P < 0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction - 0.02). There were no between-group significant differences in safety endpoints. Conclusion: The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS.