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Am Heart J. 2009 Oct;158(4):513-519.e3. doi: 10.1016/j.ahj.2009.07.028.

Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib.

Collaborators (160)

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 A, Kanakaridisz N, Márk L, Péterfai E, 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, Hoyos SJ, Araniya RC, C AG, Morales CA, Watanabe L, Arutyunov GP, Blokhin AB, Bubnova MG, Marcevich SY, Sánchez CA, Walther LA, Extremera BG, Jimenez FP, Parreño LL, 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, Barter PJ, Cannon CP, Brinton E, Davidson M, Gotto AM Jr, Hermanowski-Vosatka A, Binkowitz BS, Wittes J, Verter J, Wohlford N, Granger CB, Gersh BJ, Hasselblad V, Tonkin A.

Author information

  • 1TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. cpcannon@partners.org

Abstract

BACKGROUND:

Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date.

METHODS:

Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study.

RESULTS:

A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010.

PMID:
19781408
[PubMed - indexed for MEDLINE]
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