Title:Have We Learnt all from IMPROVE-IT? Part I. Core Results and Subanalyses on the Effects of Ezetimibe Added to Statin Therapy Related to Age, Gender and Selected Chronic Diseases (Kidney Disease, Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease)
Volume: 19
Issue: 5
Author(s): Zlatko Fras*Dimitri P. Mikhailidis
Affiliation:
- Centre for Preventive Cardiology, Department of Vascular Medicine, Division of Medicine, University Medical Centre, Ljubljana,Slovenia
Keywords:
Acute coronary syndrome, secondary prevention, low-density lipoprotein cholesterol-lowering, ezetimibe, simvastatin,
combination therapy, IMPROVE-IT Trial.
Abstract: 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.
