Low molecular weight heparin, reviparin after PTCA: results of a randomized, double-blind, standard heparin and placebo controlled multicentrical study (REDUCE Trial)

Background: Unfractionated heparin and its low molecular fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. Objectives: The specific objective of the REDUCE trial was to evaluate the effect of a low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty, Methods. The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single lesion coronary artery obstructions suitable for PTCA. Three hundred and six patients received reviparin as a 7000 U bolus before PTCA followed by 10 500 U as an infusion over 24 hours and then twice a day 3500 U s.c. application for 28 days. The 306 patients in the control group received a bolus of 10 000 U unfractionated heparin followed by an infusion of 24 000 U over 24 hours. These patients then received 28 days of s.c. placebo injections. The primary endpoints were efficacy (defined as a reduction in the incidence of major adverse events, i.e., death, myocardial infarction, need for reintervention or bypass surgery), absolute loss of minimal luminal diameter, and incidence of restenosis during the observation period of 30 weeks after PTCA. Results. Using the intention-to-treat analysis for all patients, 102 patients (33.3 %) of the reviparin group and 98 patients (32 %) of the control group have reached a primary clinical endpoint (relative risk = 0.98; 95 % confidence limit, 0.88-1.09; p = 0.707). Likewise, no difference in late loss of minimal luminal diameter was evident for either group. Acute events within 24 hrs occurred in 3.9 % of the reviparin group and in 8.2 % of the control group (relative risk = 0.49; 95 % confidence limit, 0.26-0.92; p = 0.027) during or immediately after the initial procedure. In the control group, 8 major bleedings occurred, and in the reviparin group, 7 major bleeding complications were observed within 35 days after PTCA. Conclusions: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.