Major bleeding is a powerful independent predictor of 30-day mortality in patients with ACS managed invasively. Several factors independently predict major bleeding, including treatment with heparin plus GPI compared with bivalirudin monotherapy. Knowledge of these findings might be useful to reduce bleeding risk and improve outcomes in ACS.

No abstract

Context Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5–7 days prior to surgery to minimize bleeding. Objective To evaluate the use of cangrelor, an intravenous, reversible P2Y12 platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG). Design, Setting, and Patients Prospective, randomized double-blind, placebo-controlled, multicenter trial, in patients (n=210) with an acute coronary syndrome (ACS) or treated with a coronary stent on a thienopyridine awaiting CABG to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n=11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients administered cangrelor or placebo for at least 48 hours, which was discontinued 1–6 hours prior to CABG. Main outcome measures The primary efficacy endpoint was platelet reactivity (measured in P2Y12 Reaction Units [PRU]), assessed daily with the VerifyNow™ P2Y12 assay. The main safety endpoint was excessive CABG-related bleeding. Results The dose of cangrelor determined in the open-label stage was 0.75 µg/kg/min. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary endpoint, PRU<240: 98.8% (83/84) vs. 19.0% (16/84); relative risk [RR]: 5.2, 95% confidence interval [CI]:3.3–8.1, p<0.001). Excessive CABG-related bleeding occurred in 11.8% (12/102) vs. 10.4% (10/96) in the cangrelor and placebo groups, respectively (RR=1.1, 95% CI: 0.5–2.5, p=0.763). There were no significant differences in major bleeding prior to CABG, although minor bleeding was numerically higher with cangrelor. Conclusions Among patients who must wait for cardiac surgery after thienopyridine discontinuation, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition.

No abstract

No abstract

No abstract

No abstract

SummaryIn clinical trials up to 30% of patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) experience bleeding complications, and even higher rates have been reported in contemporary practice. A growing body of data suggests a strong correlation between bleeding and both short-and long-term adverse outcomes, including mortality, which is independent of baseline characteristics and remains evident in most trials, despite variations in the definition of major bleeding. Although the value of antithrombin and antiplatelet therapy in reducing the risk of ischemic events is well established, the mechanisms of action that confer the benefits of these therapies have an inherent tendency to increase the risk of bleeding complications. As a result, characterization of baseline hemorrhagic risk is critical and must be accomplished before selecting an antithrombotic therapy. Risk factors for bleeding may be divided into two categories: nonmodifiable (including age, gender, race, weight, renal insufficiency, anemia, and acuity of presentation) and modifiable (including choice of antithrombotic therapy and PCI procedural characteristics). Of these predictive factors, the choice, dosage, and duration of the antithrombin and/or antiplatelet regimen are perhaps the most readily modifiable, especially in patients with an increased risk of bleeding. This review explores the nature of the association between bleeding and adverse outcomes, including mortality; evaluates risk factors for bleeding; and examines mechanisms for reducing bleeding complications through the selection of appropriate antithrombotic therapy.