TY - JOUR
T1 - Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial
AU - Nicholls, Stephen J.
AU - Kastelein, John J. P.
AU - Schwartz, Gregory G.
AU - Bash, Dianna
AU - Rosenson, Robert S.
AU - Cavender, Matthew A.
AU - Brennan, Danielle M.
AU - Koenig, Wolfgang
AU - Jukema, J. Wouter
AU - Nambi, Vijay
AU - Wright, R. Scott
AU - Menon, Venu
AU - Lincoff, A. Michael
AU - Nissen, Steven E.
AU - AUTHOR GROUP
AU - Hennekens, Charles
AU - Brown, W. Virgil
AU - DeMets, David
AU - Pfeffer, Marc
AU - Roleau, John
AU - Abraham, JoEllyn
AU - Gebel, James
AU - Huff, Christopher
AU - Katzan, Irene
AU - Shishehbor, Medhi
AU - Rassi, Andrew
AU - Uchino, Ken
AU - Vest, Amanda
AU - Zishiri, Edwin
AU - Heckman, Mary Jo
AU - Balog, Craig
AU - Dart, Anthony
AU - Amerena, John
AU - Prasad, Challa
AU - Farshid, Ahmad
AU - Gunalingam, Brendan
AU - Thompson, Peter
AU - Collins, Nicholas
AU - Arstall, Margaret
AU - van Gaal, William
AU - Aroney, Con
AU - Mahar, Leo
AU - Youssef, George
AU - Horowitz, John
AU - Anand, Dharmesh
AU - Rodes-Cabau, Josep
AU - Polasek, Petr
AU - Lai, Christopher
AU - Huynh, Thao
AU - Hubacek, Jaroslav
AU - Trip, Mieke D.
PY - 2014
Y1 - 2014
N2 - Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. clinicaltrials.gov Identifier: NCT01130246
AB - Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. clinicaltrials.gov Identifier: NCT01130246
U2 - https://doi.org/10.1001/jama.2013.282836
DO - https://doi.org/10.1001/jama.2013.282836
M3 - Article
C2 - 24247616
SN - 0098-7484
VL - 311
SP - 252
EP - 262
JO - JAMA
JF - JAMA
IS - 3
ER -