News:Bivalirudin during primary PCI reduces major bleeding and adverse events at 30 days in the HORIZONS-AMI trial

May 22, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

Previously bivalirudin (Angiomax, the Medicines Company), a direct thrombin inhibitor during percutaneous coronary intervention (PCI) has been demonstrated to be associated with reduced bleeding when compared with glycoprotein IIb/IIIa inhibitor plus heparin combination in the setting of non ST elevation myocardial infarction and stable angina with equivalent rates of ischemic events . The use of bivalirudin in the setting of an acute ST elevation myocardial infarction during primary PCI was evaluated in the HORIZONS-AMI trial (Harmonizing Outcomes with Revascularization and Stents in Acute myocardial infarction).

This study consisted of 3602 patients with ST segment elevation myocardial infarction from 11 countries recruited between March 25, 2005 and May 7, 2007. Patients who presented 12 hours after symptom onset underwent primary percutaneous coronary intervention and were randomized to receive bivalirudin alone (n=1800) or heparin plus glycoprotein IIb/IIIa inhibitor (n=1802). Intravenous heparin was administered at a dose of 60 IU/kg of body weight to maintain an activated clotting time of 200-250 seconds during PCI. Intravenous bivalirudin was administered at a dose of 0.75mg/kg followed by an infusion of 1.75 mg/kg/hour. Heparin and bivalirudin were discontinued following angiography or PCI unless clinically indicated to continue with this treatment. Abciximab (bolus 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min) or eptifibatide (bolus 180 μg/kg followed by an infusion of 2 μg/kg/min, with a second bolus 10 minutes after the first bolus) were administered.

Dr Stone and colleagues from Columbia University Medical center report the 30 day results of this study in the latest issue of the NEJM [1]. The primary endpoints of this study consisted of major bleeding and combined adverse cardiovascular events referred to as the net adverse clinical events including major bleeding or major adverse cardiovascular events (death, reinfarction, target vessel revascularization for ischemia), and stroke.

In the bivalirudin group, 2.6% of patients received heparin therapy and during PCI 7.5% of patients received a glycoprotein IIb/IIIa inhibitor (4.3% abciximab, 3.2% eptifibatide). The investigators report that the use of bivalirudin alone compared with GPIIb/IIIa plus heparin is associated with a significant reduction in major bleeding (4.9% vs. 8.3%; RR 0.60, 95% CI 0.46 to 0.77, p<0.001) and net adverse clinical outcomes (9.2% vs. 12.1%; RR 0.76, 95% CI 0.63 to 0.92, p=0.005) at 30 days. Bivalirudin was also associated with a significant reduction in moderate (1.1% vs. 2.9%, p=0.003), severe (0.3% vs. 0.9%, p=0.02) and profound (0 vs. 0.4%, p=0.02) thrombocytopenia.

Furthermore, treatment with bivalirudin resulted in reduced death from cardiac (1.8% vs. 2.9%; RR 0.62, 95% CI 0.40 to 0.95, p=0.03) and all causes (2.1% vs. 3.1%; RR 0.66, 95% CI 0.44 to 1.00, p=0.047) at 30 days compared with GPIIb/IIIa plus heparin treatment. Interestingly, while acute stent thrombosis (≤24 hour) was more frequently observed in the bivalirudin group compared with the glycoprotein IIb/IIIa plus heparin group (1.3% vs. 0.3%, p<0.001), there was no difference in the occurrence of subacute (>24 hour-30 days) stent thrombosis (1.2% vs. 1.7%, p=0.28) between the 2 groups respectively.

The investigators conclude that treatment with bivalirudin alone when compared with glycoprotein IIb/IIIa inhibitor plus heparin during primary PCI following a ST segment elevation myocardial infarction resulted in significant reduction in 30-day major bleeding and net adverse clinical outcomes.

Source

 * 1) Stone et al. Bivalirudin during primary PCI in acute myocardial infarction. NEJM 2008;358:2218-30