A Comparison of Recombinant Hirudin with Heparin for the Treatment of Acute Coronary Syndromes
Topic: Anticoagulation in acute coronary syndrome (direct thrombin inhibitors)
- Direct thrombin inhibitor is superior to IV unfractionated heparin in patients with unstable angina or acute myocardial infarction.
- International, multi-centered, double blinded, randomized clinical trial
- Hirudin (0.1 mg/kg IV, followed by a continuous infusion of 0.1 mg/kg/hr) with heparin placebo for 3 to 5 days.
- Note: In patients with STEMI, the decision to pursue tPA regimen vs PCI vs CABG was done at discretion of the attending physician.
- Unfractionated heparin (5000 U IV bolus, followed by a continuous infusion of 1000 U per hour) with hirudin placebo for 3 to 5 days.
- 12,142 patients (4,131 STEMIs and 8,011 NSTEMIs)
- Presenting within 12 hours of an acute MI (chest discomfort, associated with ST-segment elevation or depression >0.5 mm, T wave inversion of >1 mm in ≥2 contiguous leads, or LBBB).
- Patients taking warfarin at time of enrollment
- Active bleeding
- History of stroke
- Contraindication to heparin therapy or renal insufficiency (serum creatinine >2.0 mg/dL)
- Systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg
- Women of childbearing potential
- 30 days
- Composite outcome of death, nonfatal reinfarction, and nonfatal disabling stroke.
- Death, myocardial infarction, or disability from stroke.
- The primary composite end point was significantly lower in the hirudin at 24 hours (1.3% vs 2.1%, OR 0.61; CI 0.46 to 0.81; P=0.001), 48 hours (2.3% vs 3.1 %, OR 0.73; CI 0.59 to 0.91; P=0.001).
- At 30 days 8.9 % of the hirudin group vs 9.8 % of the heparin group had reached the primary end point (OR 0.89; CI 0.79 to 1.00; P=0.06). This effect was not influenced by ST segment status.
- The secondary composite end point of death, myocardial infarction, or disability from stroke was reached in 9.2 % of the hirudin group and 10.2% of the heparin group (P = 0.07).
- There were no significant differences between hirudin and heparin in the incidence of recurrent ischemia, heart failure, arrhythmias, or cardiogenic shock.
- There was a higher incidence of intracranial hemorrhage among patients without STsegment elevation who were treated with hirudin, as compared with those treated with heparin (0.2 percent [6 events] vs. 0.02 percent [1 event]), and a higher overall rate of moderate bleeding in the group treated with hirudin (8.8 percent vs. 7.7 percent, P = 0.03).
TAKE AWAY: Small advantage of hirudin over heparin (most pronounced in first 24 hours) without an increased risk of bleeding.
Reference: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med. 1996;335:775-782.