Bivalirudin for Patients with Acute Coronary Syndromes

Abstract

Background Current guidelines for patients with moderate-or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. Methods We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. Results Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P = 0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P = 0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). Conclusions In patients with moderate-or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158.

Efficacy and Safety of Unfractionated Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Revascularization for an Acute Coronary Syndrome: A Meta‐Analysis of Randomized Trials Performed With Stents and Thienopyridines

“…The ACUITY and HORIZONS AMI trials were excluded because these open label trials included a bivalirudin-based strategy. 42,43 Lastly, several trials used a higher dose of unfractionated heparin in the control arm than the GPI arm. This difference might have diminished the relative efficacy of GPIs and masked any increased tendency toward bleeding.…”

The impact of bleeding in patients with acute coronary syndromes: How to optimize the benefits of treatment and minimize the risk

“…In a combined analysis of the PURSUIT and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON) trials (41), 30-day and six-month mortality relate to the severity of bleeding as measured by the GUSTO scale (Figure 1). In the recent ACUITY trial (42), major bleeding occurred in 5.9% of patients, and was associated with more deaths than in those who had no major bleeding (5.4% versus 0.8%), myocardial infarction (17.1% versus 5.5%) and the need for unplanned revascularization (9.3% versus 3.0%).…”

“…This was an acceptable hazard, provided that the bleeding risk was small and that the treatment reduced ischemic outcomes. Recent studies (1,2) with newer antithrombotic agents have failed to show incremental benefits, but indicate that the same benefits can be achieved as the previous standard of care with a lower risk of bleeding. In addition, it is now recognized that both bleeding and the need for blood transfusions are associated with a major risk for recurrent ischemic coronary events and death, independent of the immediate consequence of blood loss.…”

Issues in Management of Acute Coronary Syndromes: Effects of Bleeding

“…Of these, only bivalirudin is approved for use in ACS patients undergoing PCI; 21 the other agents are approved only for patients at risk for or who develop heparin-induced thrombocytopenia. 22,23 In two large trials, bivalirudin was associated with significantly less bleeding vs. combination UFH plus GP IIb/IIIa inhibitor or enoxaparin plus GP IIb/IIIa inhibitor in ACS patients 24 and vs. UFH plus planned GP IIb/IIIa inhibition in patients undergoing PCI. 25,26 The rates of transfusion also were significantly lower in bivalirudin-treated patients in these trials.…”

“…25,26 The rates of transfusion also were significantly lower in bivalirudin-treated patients in these trials. 24,25 In both of these trials, the use of heparin or enoxaparin rather than bivalirudin was an independent predictor of major bleeding, which, in turn, was an independent predictor of the 30-day 5 and 1-year mortality. 10 Thus, the use of agents associated with lower bleeding risk is likely to improve outcomes in patients with ACS and those undergoing PCI.…”