Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial

• Published in: The American heart journal Vol. 170; no. 6; pp. 1061 - 1069
• Main Authors: Nicholls, Stephen J., MBBS, PhD, Lincoff, A. Michael, MD, Barter, Philip J., MBBS, PhD, Brewer, H. Bryan, MD, Fox, Keith A.A., MBChB, F MedSci, Gibson, C. Michael, MD, Grainger, Christopher, MD, Menon, Venugopal, MD, Montalescot, Gilles, MD, Rader, Daniel, MD, Tall, Alan R., MBBS, McErlean, Ellen, MSN, Riesmeyer, Jeffrey, MD, Vangerow, Burkhard, MD, Ruotolo, Giacomo, MD, PhD, Weerakkody, Govinda J., PhD, Nissen, Steven E., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2015; Elsevier Limited
• Subjects: Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - adverse effects; Atherosclerosis; Benzodiazepines - administration & dosage; Benzodiazepines - adverse effects; Blood pressure; Cardiovascular; Cardiovascular disease; Cerebrovascular Disorders - diagnosis; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - prevention & control; Cholesterol; Cholesterol Ester Transfer Proteins - antagonists & inhibitors; Cholesterol Ester Transfer Proteins - metabolism; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Coronary Artery Disease - diagnosis; Coronary Artery Disease - metabolism; Coronary Artery Disease - prevention & control; Double-Blind Method; Drug Monitoring; Family medical history; Female; Heart attacks; Humans; Lipids; Lipoproteins; Male; Medical imaging; Middle Aged; Mortality; Outcome Assessment (Health Care); Peripheral Vascular Diseases - diagnosis; Peripheral Vascular Diseases - metabolism; Peripheral Vascular Diseases - prevention & control; Research centers; Risk Assessment; Stroke; Studies; Triglycerides; Ultrasonic imaging
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2015.09.007

Background Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. Study Design ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. Conclusions ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.