Circulation, Vol 89, 1557-1566, Copyright © 1994 by American Heart Association
EJ Topol, V Fuster, RA Harrington, RM Califf, NS Kleiman, DJ Kereiakes, M Cohen, A Chapekis, HK Gold and MA Tannenbaum
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.
ARTICLES
Recombinant hirudin for unstable angina pectoris. A multicenter, randomized angiographic trial
Department of Cardiology, Cleveland Clinic Foundation, OH 44195.
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