Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial

Brinton, Eliot A.; Kher, Uma; Shah, Sukrut; Cannon, Christopher P.; Davidson, Michael; Gotto, Antonio M.; Ashraf, Tanya B.; McCrary Sisk, Christine; Dansky, Hayes; Mitchel, Yale; Barter, Philip; Gerstman, M.; Howes, L.; Kostner, K.; Nestel, P.; Sullivan, D.; Brath, H.; Patsch, J.; Paulweber, B.; Toplak, H.; Constance, C.M.; Howlett, E.; Mymin, D.; Pliamm, L.; Saunders, K.K.; Tardif, J.-C.; Tytus, R.; Aschner, P.; Keinänen-Klukaanniemi, S.; Strandberg, T.; Taskinen, M.-R.; Luc, G.; Richter, D.; Schlienger, J.L.; Zaïr, Y.; Appel, K.-F.; Baar, M.; Luley, C.; Overhoff, U.; Pomykaj, T.; Schaefer, T.; Lau, S.T.; Lee, K.L.F.; Tan, K.; Tomlinson, B.; Tsang, M.W.; 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.; Bin Abdul Ghapar, A.K.; Chee, K.H.; Ismail, S.B.; Ling, K.H.; Ramanathan, G.R.L.; Sim, K.H.; Alvarado, R.; Benavides, M.; Cardona, G.E.; Gonzalez, G.; Verdejo, J.; Basart, D.C.G.; Imholz, B.P.M.; Jonker, J.J.C.; Nierop, P.R.; Posma, J.L.; Twickler, Th. B.; Barrington-Ward, E.; Cutfield, R.; Friedlander, D.H.; Scott, R.S.; Istad, H.; Langslet, G.; Skjelvan, G.K.; Campodónico Hoyos, S.J.; Coloma Araniya, R.; Gallegos C., A.; Pino Morales, C.A.; Watanabe, L.; Arutyunov, G.P.; Blokhin, A.B.; Bubnova, M.G.; Marcevich, S.Y.; Álvarez Sánchez, C.; Álvarez-Sala Walther, L.A.; Gil Extremera, B.; Perez Jimenez, F.; de Teresa Parreño, L.; Anderberg, C.-P.

doi:10.1016/J.JACL.2014.10.005

Publication

Title

Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial

Author

Brinton, Eliot A.

Kher, Uma

Shah, Sukrut

Cannon, Christopher P.

Davidson, Michael

Gotto, Antonio M.

Ashraf, Tanya B.

McCrary Sisk, Christine

Dansky, Hayes

Mitchel, Yale

Barter, Philip

Gerstman, M.

Howes, L.

Kostner, K.

Nestel, P.

Sullivan, D.

Brath, H.

Patsch, J.

Paulweber, B.

Toplak, H.

More...

Institution/Organisation

DEFINE Investigators

Abstract

Background In the Determining the Efficacy and Tolerability of cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib (DEFINE) trial, anacetrapib added to statin produced robust low-density lipoprotein cholesterol (LDL-C)-lowering and high-density lipoprotein cholesterol (HDL-C)-raising vs placebo in patients with coronary heart disease (CHD). Predictors of the degree of LDL-C and HDL-C responses to anacetrapib, however, are poorly understood. Objective Lipid effects of anacetrapib in patient subgroups within the DEFINE trial (clinicaltrials.gov: NCT00685776) are reported. Methods The percent of placebo-corrected changes from baseline for LDL-C (estimated by Friedewald calculation [Fc-LDL-C]) and HDL-C after 24 weeks of anacetrapib 100 mg/day were compared among patients by age, gender, race, diabetes status, type of concomitant statin with or without other lipid therapies, and baseline HDL-C, Fc-LDL-C, and triglyceride (TG) levels. Results Percent decreases in Fc-LDL-C and increases in HDL-C with anacetrapib were similar (magnitude of difference generally <1/5 of the overall treatment effect) across subgroups by age, gender, diabetes status, lipid-modifying regimen, and baseline Fc-LDL-C, HDL-C, or TG. On the other hand, anacetrapib effects on Fc-LDL-C (−24% vs −41%) and HDL-C (+75% vs +139%) appeared to be less in black vs white patients, respectively. Conclusion Effects of anacetrapib on Fc-LDL-C and HDL-C were generally comparable across subgroups, including being relatively independent of baseline Fc-LDL-C, HDL-C, or TG levels. The clinical impact of the lipid-modifying effects of anacetrapib is being evaluated in the cardiovascular disease outcomes trial, Randomized EValuation of the Effects of Anacetrapib though Lipid-modification (REVEAL).

Language

English

Source (journal)

Journal of clinical lipidology

Publication

2015

ISSN

1933-2874

DOI

10.1016/J.JACL.2014.10.005

Volume/pages

9 :1 (2015) , p. 65-71