Zlatko Fras* and Dimitri P. Mikhailidis Pages 451 - 468 ( 18 )
IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized clinical trial (including 18,144 patients) that evaluated the efficacy of the combination of ezetimibe with simvastatin vs. simvastatin monotherapy in patients with acute coronary syndrome (ACS) and moderately increased low-density lipoprotein cholesterol (LDL-C) levels (of up to 2.6-3.2 mmol/L; 100-120 mg/dL). After 7 years of follow-up, combination therapy resulted in an additional LDL-C decrease [to 1.8 mmol/L, or 70 mg/dL, within the simvastatin (40 mg/day) monotherapy arm and to 1.4 mmol/L, or 53 mg/dL for simvastatin (40 mg/day) + ezetimibe (10 mg/day)] and showed an incremental clinical benefit [composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke; hazard ratio (HR) of 0.936, and 95% CI 0.887-0.996, p=0.016]. Therefore, for very high cardiovascular risk patients “even lower is even better” regarding LDL-C, independently of the LDL-C reducing strategy. These findings confirm ezetimibe as an option to treat very-high-risk patients who cannot achieve LDL-C targets with statin monotherapy. Additional analyses of the IMPROVE-IT (both prespecified and post-hoc) include specific very-high-risk subgroups of patients (those with previous acute events and/or coronary revascularization, older than 75 years, as well as patients with diabetes mellitus, chronic kidney disease or non-alcoholic fatty liver disease). The data from IMPROVE-IT also provide reassurance regarding longer-term safety and efficacy of the intensification of lipid-lowering therapy in very-high-risk patients resulting in very low LDL-C levels. We comment on the results of several (sub) analyses of IMPROVE-IT.
Acute coronary syndrome, secondary prevention, low-density lipoprotein cholesterol-lowering, ezetimibe, simvastatin, combination therapy, IMPROVE-IT Trial.
Centre for Preventive Cardiology, Department of Vascular Medicine, Division of Medicine, University Medical Centre, Ljubljana, Department of Clinical Biochemistry, Royal Free Hospital Campus, University College Medical School, University College London, London