Journal article
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
The New England journal of medicine, Vol.377(13), pp.1217-1227
09/28/2017
DOI: 10.1056/NEJMoa1706444
PMID: 28847206
Abstract
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).
Details
- Title: Subtitle
- Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
- Creators
- Louise Bowman - University of OxfordJemma C Hopewell - University of OxfordFang Chen - University of OxfordKarl Wallendszus - University of OxfordWilliam Stevens - University of OxfordRory Collins - Harvard UniversityStephen D Wiviott - Harvard UniversityChristopher P Cannon - Harvard UniversityEugene Braunwald - Harvard Medical SchoolEmily Sammons - University of OxfordMartin J Landray - University of OxfordHPS3/TIMI55–REVEAL Collaborative Group
- Contributors
- Jennifer G Robinson (Contributor) - University of Iowa, Fraternal Order of Eagles Diabetes Research Center
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.377(13), pp.1217-1227
- DOI
- 10.1056/NEJMoa1706444
- PMID
- 28847206
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- 18475 / Versus Arthritis MC_U137686861 / Medical Research Council MC_UU_12026/5 / Medical Research Council 18475 / Arthritis Research UK RC-PG-0407-10054 / Department of Health FS/14/55/30806 / British Heart Foundation 20639 / Versus Arthritis
- Language
- English
- Date published
- 09/28/2017
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984363625802771
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