RECOMBINANT HIRUDIN FOR UNSTABLE ANGINA-PECTORIS - A MULTICENTER, RANDOMIZED ANGIOGRAPHIC TRIAL

Background Coronary artery thrombosis plays an important pathophysiolo gical role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or c onsistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thro mbus in a manner superior to heparin. Methods and Results Patients wit h rest ischemic pain, abnormal ECG, and baseline angiogram indicating a greater than or equal to 60% stenosis of a culprit coronary artery o r saphenous vein graft with visual appearance of thrombus were randomi zed to one of two different doses of heparin (either a target activate d 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 o f study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was ch ange 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 elev ation 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-sec ond range (16% heparin versus 71% hirudin, P<.001), Overall, the 116 p atients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variabl e-the average cross-sectional area (P=.08)-as well as minimal cross-se ctional 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 i nhibition of coronary artery thrombus. Large-scale comparative trials are warranted.