Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Trix, a novel Rac guanine-nucleotide exchange factor from Dictyostelium discoideum is an actin-binding protein and accumulates at endosomes.

Small Rho family GTPases are involved in regulation of actin cytoskeleton dynamics. These molecular switches are themselves mainly controlled by specific GTPase-activating proteins (GAPs) and guanine-nucleotide exchange factors (GEFs). We have cloned and initially characterized a novel putative RhoGEF from Dictyostelium discoideum. The predicted 135-kDa protein displays a unique domain organization in its N-terminus by harboring two type3 calponin homology (CH) domains followed by a single type1 CH domain. The C-terminal region encompasses a diffuse B-cell lymphoma homology/pleckstrin homology tandem domain that is typically found in RhoGEFs. We therefore refer to this protein as Trix (triple CH-domain array exchange factor). A recombinant N-terminal region of Trix carrying all three CH domains binds to F-actin and bundles actin filaments. Trix-null mutants are viable and display only subtle defects when compared to wild-type cells with the exception of a substantial decrease in exocytosis of a fluid-phase marker. GFP fusions with the full-length protein or the N-terminal part containing all three CH domains revealed that Trix localizes to the cortical region and strongly accumulates on late endosomes. Our results suggest that Trix is specifically involved in a Rho GTPase-signaling pathway that is required for regulation of the actin cytoskeleton during exocytosis.