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Previous Volume 333:757-764 September 21, 1995 Number 12 Next

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ABSTRACT

Background The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin.

Methods We randomly assigned 1141 patients with unstable angina who were scheduled for angioplasty to receive one of three treatments: (1) a bolus dose of 10,000 IU of heparin followed by an intravenous infusion of heparin for 24 hours and subcutaneous placebo twice daily for three days (382 patients), (2) a bolus dose of 40 mg of hirudin followed by an intravenous infusion of hirudin for 24 hours and subcutaneous placebo twice daily for three days (381 patients), or (3) the same hirudin regimen except that 40 mg of hirudin was given subcutaneously instead of placebo twice daily for three days (378 patients). The primary end point was event-free survival at seven months. Other end points were early cardiac events (within 96 hours), bleeding and other complications of the study treatment, and angiographic measurements of coronary diameter at six months of follow-up.

Results At seven months, event-free survival was 67.3 percent in the group receiving heparin, 63.5 percent in the group receiving intravenous hirudin, and 68.0 percent in the group receiving both intravenous and subcutaneous hirudin (P = 0.61). However, the administration of hirudin was associated with a significant reduction in early cardiac events, which occurred in 11.0, 7.9, and 5.6 percent of patients in the respective groups (combined relative risk with hirudin, 0.61; 95 percent confidence interval, 0.41 to 0.90; P = 0.023). The mean minimal luminal diameters in the respective groups on follow-up angiography at six months were 1.54, 1.47, and 1.56 mm (P = 0.08).

Conclusions Although significantly fewer early cardiac events occurred with hirudin than with heparin, hirudin had no apparent benefit with longer-term follow-up.

Source Information

From the Academisch Ziekenhuis Dijkzigt, Rotterdam, the Netherlands (P.W.S., J.-P.R.H., V.A.W.M.U.); the Medizinische Universitätsklinik, Kiel, Germany (R.S.); the Universitätsklinik Rudolf Virchow, Berlin, Germany (W.R.); the Medizinische Klinik III, Heidelberg, Germany (C.B.); the Onze Lieve Vrouwe Gasthuis, Amsterdam (G.-J.L.); the Academisch Ziekenhuis Groningen, Groningen, the Netherlands (R.D.); the Medisch Centrum de Klokkenberg, Breda, the Netherlands (A.A.B.); the Royal Infirmary, Edinburgh, United Kingdom (K.A.A.F.); Ciba–Geigy Ltd., Basel, Switzerland (P.C.); and Cardialysis B.V., Rotterdam, the Netherlands (J.W.D.).

Address reprint requests to Dr. Serruys at the Thoraxcenter, Erasmus University, Rm. EE 2332, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands.

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