A COMPARISON OF HIRUDIN WITH HEPARIN IN THE PREVENTION OF RESTENOSIS AFTER CORONARY ANGIOPLASTY

Background. The likelihood of restenosis is a major limitation of coro nary angioplasty. We studied whether hirudin, a highly selective inhib itor of thrombin with irreversible effects, would prevent restenosis a fter angioplasty. We compared two regimens of recombinant hirudin with heparin. Methods. We randomly assigned 1141 patients with unstable an gina who were scheduled for angioplasty to receive one of three treatm ents: (1) a bolus dose of 10,000 IU of heparin followed by an intraven ous infusion of heparin for 24 hours and subcutaneous placebo twice da ily for three days (382 patients), (2) a bolus dose of 40 mg of hirudi n followed by an intravenous infusion of hirudin for 24 hours and subc utaneous placebo twice daily for three days (381 patients), or (3) the same hirudin regimen except that 40 mg of hirudin was given subcutane ously instead of placebo twice daily for three days (378 patients). Th e primary end point was event-free survival at seven months. Other end points were early cardiac events (within 96 hours), bleeding and othe r complications of the study treatment, and angiographic measurements of coronary diameter at six months of follow-up. Results. At seven mon ths, event-free survival was 67.3 percent in the group receiving hepar in, 63.5 percent in the group receiving intravenous hirudin, and 68.0 percent in the group receiving both intravenous and subcutaneous hirud in (P=0.61). However, the administration of hirudin was associated wit h a significant reduction in early cardiac events, which occurred in 1 1.0, 7.9, and 5.6 percent of patients in the respective groups (combin ed 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 respe ctive groups on follow-up angiography at six months were 1.54, 1.47, a nd 1.56 mm (P=0.08). Conclusions. Although significantly fewer early c ardiac events occurred with hirudin than with heparin, hirudin had no apparent benefit with longer-term follow-up.