4 research outputs found
Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial
IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: 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). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas 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. RESULTS: 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). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved
Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome - Results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study
Background: Angiotensin-converting enzyme inhibitors
reduce mortality and remodeling after myocardial
infarction in patients with left ventricular dysfunction.
Methods: Perindopril and Remodeling in Elderly With
Acute Myocardial Infarction (PREAMI), a doubleblind,
randomized, parallel-group, multicenter, placebocontrolled
study, determined whether similar benefits occur
in elderly postinfarction patients with preserved left
ventricular function. A total of 1252 patients 65 years or
older with a left ventricular ejection fraction of 40% or
higher and recent acute myocardial infarction were randomized
to receive perindopril erbumine or placebo (8
mg/d) for 12 months. The combined primary end point
was death, hospitalization for heart failure, or left ventricular
remodeling. Secondary end points included cardiovascular
death, hospitalization for reinfarction or angina,
and revascularization.
Results: The primary end point occurred in 181 patients
(35%) taking perindopril and 290 patients (57%)
taking placebo, with a significant absolute risk reduction
of 0.22 (95% confidence interval, 0.16 to 0.28;
P.001). A total of 126 patients (28%) and 226 patients
(51%) in the perindopril and placebo groups, respectively,
experienced remodeling. The mean increase in left
ventricle end-diastolic volume was 0.7 mL with perindopril
compared with 4.0 mL with placebo (P.001). In
the perindopril group, 40 deaths (6%) and 22 hospitalizations
(4%) for heart failure occurred, whereas 37 deaths
(6%) and 30 hospitalizations (5%) occurred in the placebo
group. Treatment did not affect death, whereas the
hospitalization rate for heart failure was slightly reduced
(absolute risk reduction, 0.01; 95% confidence interval,
−0.01 to 0.02). No treatment effect on other secondary
end points was detected.
Conclusion:Wefound that 1-year treatment with 8mg/d
of perindopril reduces progressive left ventricular remodeling
that can occur even in the presence of small
infarct size, but it was not associated with better clinical
outcomes