Recombinant hirudin tended to improve the average cross-sectional area of the culprit lesion more than heparin (P=0.08), and significantly improved minimal luminal diameter (P=0.029).
RCT (n=166)
randomized
Yes
Does recombinant hirudin improve angiographic culprit lesion dimensions compared to heparin in patients with unstable angina and visible coronary thrombus?
Recombinant hirudin appears to be a promising antithrombotic alternative to heparin for inhibiting coronary artery thrombus in unstable angina, improving some angiographic lesion dimensions.
p-value: p=0.08
BACKGROUND: Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin. METHODS AND RESULTS: Patients with rest ischemic pain, abnormal ECG, and baseline angiogram indicating a > or = 60% stenosis of a culprit coronary artery or saphenous vein graft with visual appearance of thrombus were randomized to one of two different doses of heparin (either a target activated partial thromboplastin time aPTT of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 infusion) in a dose-escalating protocol. After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was change in the average cross-sectional area of the culprit lesion. Other efficacy end points also involved changes in culprit lesion dimensions and TIMI flow grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin, P < .001). Overall, the 116 patients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variable--the average cross-sectional area (P = .08)--as well as minimal cross-sectional area (P = .028), minimal luminal diameter (P = .029), and percent diameter stenosis (P = .07). CONCLUSIONS: Recombinant hirudin appears to be a promising antithrombotic intervention compared with heparin for inhibition of coronary artery thrombus. Large-scale comparative trials are warranted.
Topol et al. (Fri,) conducted a rct in unstable angina pectoris (n=166). Recombinant hirudin vs. heparin was evaluated on change in the average cross-sectional area of the culprit lesion (p=0.08). Recombinant hirudin tended to improve the average cross-sectional area of the culprit lesion more than heparin (P=0.08), and significantly improved minimal luminal diameter (P=0.029).