A Comparison of Hirudin with Heparin in the Prevention of Restenosis after Coronary Angioplasty
Patrick W. Serruys, M.D., Ph.D., Jean-Paul R. Herrman, M.D., Rudiger Simon, M.D., Wolfgang Rutsch, M.D., Christoph Bode, M.D., Gert-Jan Laarman, M.D., Ph.D., Rene van Dijk, M.D., Arjan A. van den Bos, M.D., Victor A.W.M. Umans, M.D., Ph.D., Keith A.A. Fox, M.D., Philip Close, M.D., Jaap W. Deckers, M.D., Ph.D., for The Helvetica Investigators
Background The likelihood of restenosis is a major limitationof coronary angioplasty. We studied whether hirudin, a highlyselective inhibitor of thrombin with irreversible effects, wouldprevent restenosis after angioplasty. We compared two regimensof recombinant hirudin with heparin.
Methods We randomly assigned 1141 patients with unstable anginawho were scheduled for angioplasty to receive one of three treatments:(1) a bolus dose of 10,000 IU of heparin followed by an intravenousinfusion of heparin for 24 hours and subcutaneous placebo twicedaily for three days (382 patients), (2) a bolus dose of 40mg of hirudin followed by an intravenous infusion of hirudinfor 24 hours and subcutaneous placebo twice daily for threedays (381 patients), or (3) the same hirudin regimen exceptthat 40 mg of hirudin was given subcutaneously instead of placebotwice daily for three days (378 patients). The primary end pointwas event-free survival at seven months. Other end points wereearly cardiac events (within 96 hours), bleeding and other complicationsof the study treatment, and angiographic measurements of coronarydiameter at six months of follow-up.
Results At seven months, event-free survival was 67.3 percentin the group receiving heparin, 63.5 percent in the group receivingintravenous hirudin, and 68.0 percent in the group receivingboth intravenous and subcutaneous hirudin (P = 0.61). However,the administration of hirudin was associated with a significantreduction in early cardiac events, which occurred in 11.0, 7.9,and 5.6 percent of patients in the respective groups (combinedrelative risk with hirudin, 0.61; 95 percent confidence interval,0.41 to 0.90; P = 0.023). The mean minimal luminal diametersin the respective groups on follow-up angiography at six monthswere 1.54, 1.47, and 1.56 mm (P = 0.08).
Conclusions Although significantly fewer early cardiac eventsoccurred with hirudin than with heparin, hirudin had no apparentbenefit 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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