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

Higher 30-day readmission rate for suspicion of ACS : effect of kidney function

Background: Current evidence suggests prolonged hospitalization for Acute Coronary Syndrome (ACS) in the setting of chronic kidney disease (CKD). What remains unclear is the impact of CKD on 30-day readmission rate for suspected ACS. Methods: All patients who came to the emergency department (ED) from 2004 to 2010 and had cardiac Troponin measurement were included. Poisson regression was used to compare 30-day readmission rates between CKD stages after adjusting for age, gender, race, myocardial infarction, diabetes, hypertension and congestive heart failure at !rst admission. Results: Of 85,055 patients studied, 51.2% were admitted as In-patient, 13.3% as Observation and 35.5% were discharged directly from the ED (not admitted). Overall 6.2% were readmitted for suspected ACS within 30 days. The crude 30-day readmission rate was 51.6 per 1,000 person-days for GFR"60 mL/min/1.73 m2, 96.2 for GFR 30-59, 140.2 for GFR 15-29 and 160.0 for GFR<15. The readmission rates followed the same pattern whether patients were In-patient, Observation or discharged directly from the ED (Figure1). The adjusted 30-day readmission rate for patients with GFR<15 was almost twice as high as the rate for patients with GFR"60 [incidence rate ratio (IRR):1.9, 95% CI=1.6- 2.2]. The IRRs for patients with GFR 15-29 and 30-59 were respectively 1.6 (1.4- 1.8) and 1.2 (1.2- 1.3). Conclusion: Readmission for suspected ACS occurs more often in patients with CKD. Close monitoring may provide opportunities to reduce cost and improve outcomes

CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia (CERTAINTY)

International audienceBetter models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor . The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation