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

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Hungarian Scientific Research Fund (OTKA, PD100648 (AP)) Technology Innovation Fund, National Developmental Agency (KTIA-AIK-2012-12-1-0010). AP is the recipient of a “Lendület” grant from the Hungarian Academy of Sciences

Increased Risk of Unfavorable Metabolic Outcome during Short-Term Follow-Up in Subjects with Nonfunctioning Adrenal Adenomas

Objective: To demonstrate long-term changes in the prevalence of several types of metabolic derangements in subjects with nonfunctioning adrenal adenomas. Subjects and Methods: 273 subjects with adrenal adenomas, including 231 with nonfunctioning adenoma and 42 with subclinical Cushing's syndrome (sCS), were evaluated with respect to anthropometric and laboratory characteristics and prevalence of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, metabolic syndrome (MS), prediabetes and cardiovascular disease (CVD). Median duration was 24 months. Follow-up data of 114 participants with nonfunctioning adrenal adenomas are also presented while those of 117 were missing. Follow-up data regarding changes in anthropometric and laboratory parameters and prevalence rates of metabolic disturbances were obtained from the medical records. Results: The prevalence rates for both patients with nonfunctioning adenoma and sCS were: dyslipidemia: 161 (59%), hypertension: 147 (54%), MS: 128 (47%), prediabetes: 62 (23%), T2DM: 49 (18%), and CVD: 21 (8%). Hypertension and CVD were prevalent in subjects with sCS compared to participants with nonfunctioning adenoma. In follow-up, body mass index (p = 0.005), systolic blood pressure (p < 0.001), waist circumference (p = 0.005), homeostasis model assessment (p = 0.046), high-sensitivity C-reactive protein (p = 0.023), total cholesterol (p < 0.001) and low-density lipoprotein cholesterol (p < 0.001) and prevalence of hypertension (p < 0.001), dyslipidemia (p < 0.001), prediabetes (p < 0.001) and MS (p < 0.01) significantly increased in subjects with nonfunctioning adenoma. Conclusion: The data showed that nonfunctioning adrenal adenomas were associated with the development or deterioration of atherosclerotic risk factors. Therefore, follow-up and management strategies should be developed to decrease atherosclerotic morbidity in those individuals. Copyright (c) 2012 S. Karger AG, Base