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

被引:173
作者
TOPOL, EJ
FUSTER, V
HARRINGTON, RA
CALIFF, RM
KLEIMAN, NS
KEREIAKES, DJ
COHEN, M
CHAPEKIS, A
GOLD, HK
TANNENBAUM, MA
RAO, AK
DEBOWEY, D
SCHWARTZ, D
HENIS, M
CHESEBRO, J
机构
[1] DUKE UNIV,MED CTR,DIV CARDIOL,DURHAM,NC 27710
[2] MASSACHUSETTS GEN HOSP,DIV CARDIOL,BOSTON,MA 02114
[3] BAYLOR COLL MED,DIV CARDIOL,HOUSTON,TX 77030
[4] HAHNEMANN HOSP,PHILADELPHIA,PA
[5] CHRIST HOSP,CINCINNATI,OH 45219
[6] RIVERSIDE METHODIST HOSP,COLUMBUS,OH 43214
[7] IOWA HEART CTR,DES MOINES,IA
[8] TEMPLE UNIV,THROMBOSIS RES CTR,PHILADELPHIA,PA 19122
关键词
ANGINA; THROMBOSIS; THROMBIN; HIRUDIN; ANTICOAGULANTS;
D O I
10.1161/01.CIR.89.4.1557
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 greater than or equal to 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.
引用
收藏
页码:1557 / 1566
页数:10
相关论文
共 32 条
[31]  
ZOLDHELYI P, IN PRESS CIRCULATION
[32]  
1990, LANCET, V336, P827