Bivalirudin for Patients with Acute Coronary Syndromes
Topic: Anticoagulation in acute coronary syndrome (direct thrombin inhibitors)
Aim:
- Evaluate the role of bivalirudin in moderate to high risk ACS treated with early invasive strategy and optimal antiplatelet therapy.
Design:
- Prospective, multi-centered, open labeled, randomized clinical trial
Treatment 1:
- Bivalirudin (IV bolus of 0.1 mg/kg plus infusion of 0.25 mg/kg/hr) plus a glycoprotein IIb/IIIa inhibitor.
Treatment 2:
- Bivalirudin (IV bolus of 0.1 mg/kg plus infusion of 0.25 mg/kg/hr) alone.
Control:
- Unfractionated heparin (ACT guided 60 U/kg bolus plus 12 U/kg/hr) or enoxaparin (1mg/kg SQ twice daily prior to angiography) plus a glycoprotein IIb/IIIa inhibitor.
Cohort:
- 13,819 patients
Inclusion criteria:
- >18 years old with unstable angina symptoms lasting at least 10 minutes occurring within 24 hours before enrollment
- At least 1 of the following: new ST-segment depression or transient elevation of at least 1 mm, troponin or creatinine kinase elevation, known CAD, high TIMI risk score for unstable angina
Exclusion criteria:
- STEMI or cardiogenic shock
- Major bleed within 2 weeks prior to angina
- Thrombocytopenia
- Creatinine clearance <30 mL/min
- Recent anticoagulation use
Follow up:
- 30 days
Primary endpoint:
- Composite ischemia end point (death from any cause, myocardial infarction, or unplanned revascularization for ischemia), major bleeding (not related to CABG; e.g. CNS bleed, access site hemorrhage, >5 cm hematoma, 4 g drop in hemoglobin, reoperation for bleeding, transfusion of blood product), and a net clinical outcome end point (defined as the occurrence of the composite ischemia end point or major bleeding).
Secondary endpoint:
- None reported.
Main results:
- Mean age 63, 70% were men.
- 99% received angiography at median 19.6 hours, 56% of which underwent PCI, 11% underwent CABG, and 33% were treated medically.
- Bivalirudin plus glycoprotein IIb/IIIa inhibitors, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%; P=0.39; RR, 1.07; CI 0.92-1.23), major bleeding (5.3% and 5.7%; P=0.38; RR 0.93; CI 0.78 to 1.10), and the net clinical outcome end point (11.8% and 11.7%; P=0.93; RR 1.01; CI 0.90-1.12).
- Bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; RR 1.08; CI 0.93-1.24), a significantly reduced rate of major bleeding (3.0% and 5.7%; P<0.001; RR 0.53; CI 0.43-0.65), and a reduced rate of the net clinical outcome end point (10.1% and 11.7%; P=0.02; RR 0.86; CI 0.77-0.97).
- Bivalirudin monotherapy also decreased the rates of bleeding from any cause (including bleeding related to CABG), minor bleeding, major and minor bleeding according to the TIMI scale, and blood transfusion.
TAKE AWAY: In NSTEMI or UA treated with early invasive strategy, rates of ischemic events and bleeding were similar with use of bivalirudin or heparin when combined with planned use of glycoprotein IIb/IIIa inhibitor. Bivalirudin alone had significantly less bleeding, and may be optimized further when clopidogrel is administered prior to angiography.
