Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes

BACKGROUND Vorapaxar is a new oral protease-activated receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5010 vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

A hymenopterists' guide to the Hymenoptera Anatomy Ontology: utility, clarification, and future directions

Hymenoptera exhibit an incredible diversity of phenotypes, the result of similar to 240 million years of evolution and the primary subject of more than 250 years of research. Here we describe the history, development, and utility of the Hymenoptera Anatomy Ontology (HAO) and its associated applications. These resources are designed to facilitate accessible and extensible research on hymenopteran phenotypes. Outreach with the hymenopterist community is of utmost importance to the HAO project, and this paper is a direct response to questions that arose from project workshops. In a concerted attempt to surmount barriers of understanding, especially regarding the format, utility, and development of the HAO, we discuss the roles of homology, "preferred terms", and "structural equivalency". We also outline the use of Universal Resource Identifiers (URIs) and posit that they are a key element necessary for increasing the objectivity and repeatability of science that references hymenopteran anatomy. Pragmatically, we detail a mechanism (the "URI table") by which authors can use URIs to link their published text to the HAO, and we describe an associated tool (the "Analyzer") to derive these tables. These tools, and others, are available through the HAO Portal website (http://portal.hymao.org). We conclude by discussing the future of the HAO with respect to digital publication, cross-taxon ontology alignment, the advent of semantic phenotypes, and community-based curation.