LOW-MOLECULAR-WEIGHT HEPARIN (REVIPARIN) IN PERCUTANEOUS TRANSLUMINALCORONARY ANGIOPLASTY - RESULTS OF A RANDOMIZED, DOUBLE-BLIND, UNFRACTIONATED HEPARIN AND PLACEBO-CONTROLLED, MULTICENTER TRIAL (REDUCE TRIAL)

Objectives. The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occur rence of restenosis in patients undergoing percutaneous transluminal c oronary angioplasty (PTCA). Background. Unfractionated heparin and its low molecular weight 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. Methods. The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Can ada enrolled 625 patients with single lesion coronary artery obstructi ons suitable for PTCA. Three hundred six patients received reviparin a s a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion ove r 24 h and then twice-daily 3,500-U subcutaneous application for 28 da ys. The 306 patients in the control group received a bolus of 10,000 U of unfractionated heparin followed by an infusion of 24,000 U over 24 h. These patients then underwent 28 days of subcutaneous placebo inje ctions. The primary end points were efficacy (defined as a reduction i n the incidence of major adverse events [i.e., death, myocardial infar ction, need for reintervention or bypass surgery]), absolute loss of m inimal lumen diameter and incidence of restenosis during the observati on period of 30 weeks after PTCA. Results. Using the intention to trea t analysis for all patients, 102 (33.3%) in the reviparin group and 98 (32%) in the control group have reached a primary clinical end point (relative risk [RR] 1.04, 95% confidence interval [CI] 0.83 to 1.31, p = 0.707). Likewise, no difference in late loss of minimal lumen diame ter was evident for both groups. Acute events within 24 h occurred in 12 patients (3.9%) in the reviparin group and 25 (8.2%) in the control group (RR 0.49, 95% CI 0.26 to 0.92, p = 0.027) during or immediately after the initial procedure. In the control group, eight major bleedi ng complications occurred, and in the reviparin group, seven were obse rved within 35 days after PTCA. Conclusions. Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clin ical events or the incidence of angiographic restenosis over 30 weeks.