Format

Send to:

Choose Destination
See comment in PubMed Commons below
N Engl J Med. 2010 Dec 16;363(25):2406-15. doi: 10.1056/NEJMoa1009744. Epub 2010 Nov 17.

Safety of anacetrapib in patients with or at high risk for coronary heart disease.

Collaborators (166)

Barter PJ, Cannon CP, Brinton E, Davidson M, Gotto AM Jr, Mitchel Y, Dansky HM, Binkowitz B, Chaitman B, Dreifus L, Vetrovec G, Adams H, Mohr JP, Zivin J, Granger CB, Gersh BJ, Hasselblad V, Tonkin A, Verter J, Wohlford N, Gerstman M, Howes L, Kostner K, Nestel P, Sullivan D, Brath H, Patsch J, Paulweber B, Toplak H, Constance CM, Howlett E, Mymin D, Pliamm L, Saunders KK, Tardif JC, Tytus R, Aschner P, Keinänen-Klukaanniemi S, Strandberg T, Taskinen MR, Luc G, Richter D, Schlienger JL, Zaïr Y, Appel KF, Baar M, Luley C, Overhoff U, Pomykaj T, Schaefer T, Lau ST, Lee KL, Tan K, Tomlinson B, Tsang MW, Badacsonyi K, Kalina Á, Kanakaridisz N, Márk L, Péterfai É, Regos L, Reiber I, Takács J, Vértes A, Elis A, Gavish D, Harats D, Hussein O, Hayek T, Leitersdorf E, Ghapar AK, Chee KH, Ismail SB, Ling KH, Ramanathan GR, Sim KH, Alvarado R, Benavides M, Cardona GE, Gonzalez G, Verdejo J, Basart DC, Imholz BP, Jonker JJ, Nierop PR, Posma JL, Twickler TB, Barrington-Ward E, Cutfield R, Friedlander DH, Scott RS, Istad H, Langslet G, Skjelvan GK, Campodónico Hoyos SJ, Coloma Araniya R, Gallegos C A, Pino Morales CA, Watanabe L, Arutyunov GP, Blokhin AB, Bubnova MG, Marcevich SY, Álvarez Sánchez C, Álvarez-Sala Walther LA, Gil Extremera B, Perez Jimenez F, de Teresa Parreño L, Anderberg CP, Hedin U, Hellberg A, Höök P, Kjellström T, Nilsson P, Olsson AG, Rosenqvist U, Tolagen K, Wolff T, Baskin A, Bays HE, Bernstein RI, Bittar N, Brinton EA, Chee LH, Cottiero RA, D'Agostino RD, Davidson MH, Denker PS, Garcia RK, Hippert RK, Isakov T, Kaster SR, Kerzner B, Klein EJ, Koren MJ, Kutner ME, Liljenquist D, Lorch DG Jr, Lorraine R, Lubin BC, Lunde NM, Majchrzak TJ, McKenney JM, Mukherjee S, Muse DD, Otruba MS, Pappas JE, Patrick K, Powell SJ, Riffer E, Rink LD, Rohlf JL, Rosen JB, Rosenbilt PD, Roth EM, Rubenstein CJ, Rubino J, Rudolph LA, Schneider A, Short WG, Silverfield JC, Suresh DP, Tarshis GA, Toth PD, Townsend RW, Wahl TO.

Abstract

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.).

PMID:
21082868
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Write to the Help Desk