| Safety of anacetrapib in patients with or at high risk for coronary heart disease. | |
| | |
MedLine Citation:
|
PMID: 21082868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Anacetrapib is a cholesteryl ester transfer protein inhibitor that raises high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease or at high risk for coronary heart disease. Eligible patients who were taking a statin and who had an LDL cholesterol level that was consistent with that recommended in guidelines were assigned to receive 100 mg of anacetrapib or placebo daily for 18 months. The primary end points were the percent change from baseline in LDL cholesterol at 24 weeks (HDL cholesterol level was a secondary end point) and the safety and side-effect profile of anacetrapib through 76 weeks. Cardiovascular events and deaths were prospectively adjudicated. RESULTS: A total of 1623 patients underwent randomization. By 24 weeks, the LDL cholesterol level had been reduced from 81 mg per deciliter (2.1 mmol per liter) to 45 mg per deciliter (1.2 mmol per liter) in the anacetrapib group, as compared with a reduction from 82 mg per deciliter (2.1 mmol per liter) to 77 mg per deciliter (2.0 mmol per liter) in the placebo group (P<0.001)--a 39.8% reduction with anacetrapib beyond that seen with placebo. In addition, the HDL cholesterol level increased from 41 mg per deciliter (1.0 mmol per liter) to 101 mg per deciliter (2.6 mmol per liter) in the anacetrapib group, as compared with an increase from 40 mg per deciliter (1.0 mmol per liter) to 46 mg per deciliter (1.2 mmol per liter) in the placebo group (P<0.001)--a 138.1% increase with anacetrapib beyond that seen with placebo. Through 76 weeks, no changes were noted in blood pressure or electrolyte or aldosterone levels with anacetrapib as compared with placebo. Prespecified adjudicated cardiovascular events occurred in 16 patients treated with anacetrapib (2.0%) and 21 patients receiving placebo (2.6%) (P = 0.40). The prespecified Bayesian analysis indicated that this event distribution provided a predictive probability (confidence) of 94% that anacetrapib would not be associated with a 25% increase in cardiovascular events, as seen with torcetrapib. CONCLUSIONS: Treatment with anacetrapib had robust effects on LDL and HDL cholesterol, had an acceptable side-effect profile, and, within the limits of the power of this study, did not result in the adverse cardiovascular effects observed with torcetrapib. (Funded by Merck Research Laboratories; ClinicalTrials.gov number, NCT00685776.). |
| | |
Authors:
|
Christopher P Cannon; Sukrut Shah; Hayes M Dansky; Michael Davidson; Eliot A Brinton; Antonio M Gotto; Michael Stepanavage; Sherry Xueyu Liu; Patrice Gibbons; Tanya B Ashraf; Jennifer Zafarino; Yale Mitchel; Philip Barter; |
Related Documents
:
|
11444418 - Hypocholesterolemic effect of an enteric-coated garlic supplement. 1954418 - Dietary reduction of serum cholesterol concentration: time to think again. 19017418 - Probiotics and dietary counselling contribute to glucose regulation during and after pr... 9085948 - The influence of chronic hypokalemia on myocardial adrenergic receptor densities: enhan... 3606708 - The effects of polyoxyethylated cholesterol feeding on hepatic cholesterol synthesis an... 16162528 - Welfare assessment based on metabolic and endocrine aspects in primiparous cows milked ... |
Publication Detail:
|
Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-11-17 |
Journal Detail:
|
Title: The New England journal of medicine Volume: 363 ISSN: 1533-4406 ISO Abbreviation: N. Engl. J. Med. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-12-16 Completed Date: 2010-12-21 Revised Date: 2011-01-06 |
Medline Journal Info:
|
Nlm Unique ID: 0255562 Medline TA: N Engl J Med Country: United States |
Other Details:
|
Languages: eng Pagination: 2406-15 Citation Subset: AIM; IM |
Affiliation:
|
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. cpcannon@partners.org |
| Data Bank Information | |
Bank Name/Acc. No.:
|
ClinicalTrials.gov/NCT00685776 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Aged Anticholesteremic Agents / adverse effects, therapeutic use* Bayes Theorem Cholesterol Ester Transfer Proteins / antagonists & inhibitors* Cholesterol, HDL / blood* Cholesterol, LDL / blood* Combined Modality Therapy Coronary Disease / blood, diet therapy, drug therapy* Double-Blind Method Female Humans Male Middle Aged Oxazolidinones / adverse effects, therapeutic use* Risk Factors Young Adult |
| Chemical | |
Reg. No./Substance:
|
0/Anticholesteremic Agents; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Oxazolidinones; 0/anacetrapib |
| Investigator | |
Investigator/Affiliation:
|
Philip J Barter / ; Christopher P Cannon / ; Eliot Brinton / ; Michael Davidson / ; Antonio M Gotto / ; Yale Mitchel / ; Hayes M Dansky / ; Bruce Binkowitz / ; Bernard Chaitman / ; Leonard Dreifus / ; George Vetrovec / ; Harold Adams / ; Jay P Mohr / ; Justin Zivin / ; Christopher B Granger / ; Bernard J Gersh / ; Victor Hasselblad / ; Andrew Tonkin / ; Joel Verter / ; Neil Wohlford / ; M Gerstman / ; L Howes / ; K Kostner / ; P Nestel / ; D Sullivan / ; H Brath / ; J Patsch / ; B Paulweber / ; H Toplak / ; C M Constance / ; E Howlett / ; D Mymin / ; L Pliamm / ; K K Saunders / ; J-C Tardif / ; R Tytus / ; P Aschner / ; S Keinänen-Klukaanniemi / ; T Strandberg / ; M-R Taskinen / ; G Luc / ; D Richter / ; J L Schlienger / ; Y Zaïr / ; K-F Appel / ; M Baar / ; C Luley / ; U Overhoff / ; T Pomykaj / ; T Schaefer / ; S T Lau / ; K L F Lee / ; K Tan / ; B Tomlinson / ; M W Tsang / ; K Badacsonyi / ; Á Kalina / ; N Kanakaridisz / ; L Márk / ; É Péterfai / ; L Regos / ; I Reiber / ; J Takács / ; A Vértes / ; A Elis / ; D Gavish / ; D Harats / ; O Hussein / ; T Hayek / ; E Leitersdorf / ; A K Bin Abdul Ghapar / ; K H Chee / ; S B Ismail / ; K H Ling / ; G R L Ramanathan / ; K H Sim / ; R Alvarado / ; M Benavides / ; G E Cardona / ; G Gonzalez / ; J Verdejo / ; D C G Basart / ; B P M Imholz / ; J J C Jonker / ; P R Nierop / ; J L Posma / ; Th B Twickler / ; E Barrington-Ward / ; R Cutfield / ; D H Friedlander / ; R S Scott / ; H Istad / ; G Langslet / ; G K Skjelvan / ; S J Campodónico Hoyos / ; R Coloma Araniya / ; A Gallegos C / ; C A Pino Morales / ; L Watanabe / ; G P Arutyunov / ; A B Blokhin / ; M G Bubnova / ; S Y Marcevich / ; C Álvarez Sánchez / ; L A Álvarez-Sala Walther / ; B Gil Extremera / ; F Perez Jimenez / ; L de Teresa Parreño / ; C-P Anderberg / ; U Hedin / ; A Hellberg / ; P Höök / ; T Kjellström / ; P Nilsson / ; A G Olsson / ; U Rosenqvist / ; K Tolagen / ; T Wolff / ; A Baskin / ; H E Bays / ; R I Bernstein / ; N Bittar / ; E A Brinton / ; L H K Chee / ; R A Cottiero / ; R D D'Agostino / ; M H Davidson / ; P S Denker / ; R K Garcia / ; R K Hippert / ; T Isakov / ; S R Kaster / ; B Kerzner / ; E J Klein / ; M J Koren / ; M E Kutner / ; D Liljenquist / ; D G Lorch / ; R Lorraine / ; B C Lubin / ; N M Lunde / ; T J Majchrzak / ; J M McKenney / ; S Mukherjee / ; D D Muse / ; M S Otruba / ; J E Pappas / ; K Patrick / ; S J Powell / ; E Riffer / ; L D Rink / ; J L Rohlf / ; J B Rosen / ; P D Rosenbilt / ; E M Roth / ; C J Rubenstein / ; J Rubino / ; L A Rudolph / ; A Schneider / ; W G Short / ; J C Silverfield / ; D P Suresh / ; G A Tarshis / ; P D Toth / ; R W Townsend / ; T O Wahl / |
| Comments/Corrections | |
Comment In:
|
Nat Rev Cardiol. 2011 Jan;8(1):5 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A practical guide for estimating rates of heterolysis reactions (†).
Next Document: Stroke? Localized, otogenic meningitis!