Rationale and design of the EMBRACE STEMI study: a phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability and efficacy of intravenous Bendavia on reperfusion injury in patients treated with standard therapy including primary percutaneous coronary intervention and stenting for ST-segment elevation myocardial infarction.

BACKGROUND: Although significant efforts have been made to improve ST-segment elevation myocardial infarction (STEMI) outcomes by reducing symptom-onset-to-reperfusion times, strategies to decrease the clinical impact of ischemic reperfusion injury have demonstrated limited success. Bendavia, an intravenously administered mitochondrial targeting peptide, has been shown to reduce myocardial infarct size and attenuate coronary no-reflow in experimental modelswhen given before reperfusion. DESIGN: The EMBRACE STEMI study is a phase 2a, randomized, double-blind, placebo-controlled trial enrolling 300 patients with a first-time anterior STEMI and an occluded proximal or mid-left anterior descending artery undergoing primary percutaneous coronary intervention (PCI) within 4 hours of symptom onset. Patients will be randomized to receive either Bendavia at 0.05 mg/kg per hour or an identically appearing placebo administered as an intravenous infusion at 60 mL/h. The primary end point is infarct size measured by the area under the creatine kinase-MB enzyme curve calculated from measurements from the central clinical chemistry laboratory obtained over the initial 72 hours after the primary PCI procedure, and the major secondary end point is infarct size calculated by the volume of infarcted myocardium (late contrast gadolinium enhancement) on the day 4±1 cardiac magnetic resonance imaging. SUMMARY: EMBRACE-STEMI is testing the hypothesis that Bendavia, in conjunction with standard-of-care therapy, is superior to placebo for the reduction of myocardial infarction size among patients with first time, acute, anterior wall STEMI who undergo successful reperfusion with primary PCI and stenting.

Triple Antiplatelet Therapy and Combinations with Oral Anticoagulants After Stent Implantation.

Triple oral anticoagulation or triple antiplatelet therapies may be administered for various reasons. They reduce cardiac complications following percutaneous coronary intervention and stroke or other thromboembolic phenomenon in conditions such as atrial fibrillation. There is an elevated risk of severe bleeding, so it is necessary to balance risk and benefits. Newer oral anticoagulants and antiplatelet drugs may be considered; the number of options is increasing. This article examines triple therapies and the efficacy and safety of combinations of traditional anticoagulant and antiplatelet drugs, and reviews clinical trial data on novel agents. Guidelines to inform clinical decision-making are presented.