Author + information
- Received March 26, 1996
- Revision received July 11, 1996
- Accepted July 17, 1996
- Published online November 15, 1996.
- Karl R. Karsch, MD, FESC, FACC∗∗,
- Melitta B. Preisack, MD∗,
- Rainer Baildon, MD∗,
- Volker Eschenfelder, MD∗,
- David Foley, MD∗,
- Eulogio J. Garcia, MD†,
- Martin Kaltenbach, MD‡,
- Christoph Meisner, MA∗,
- Hans K. Selbmann, PhD∗,
- Patrick W. Serruys, MD, FACC§,
- Man F. Shiu, MD∥,
- Martin Sujatta, MD∗,
- Raoul Bonan, MD¶,g,
- REDUCE Trial Group#
- ↵∗Address for correspondence: Dr. Karl R. Karsch, Department of Cardiology, Tübingen University, Otfried-Müller Strasse 10, 72076 Tübingen, Germany.
Objectives. The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary 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 Canada enrolled 625 patients with single-lesion coronary artery obstructions suitable for PTCA. Three hundred six patients received reviparin as a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion over 24 h and then twice-daily 3,500-U subcutaneous application for 28 days. 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 injections. The primary end points were efficacy (defined as a reduction in the incidence of major adverse events [i.e., death, myocardial infaction, need for reintervention or bypass surgery]), absolute loss of minimal lumen 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 (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 diameter 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% Cl 0.26 to 0.92, p = 0.027) during or immediately after the initial procedure. In the control group, eight major bleeding complications occurred, and in the reviparin group, seven 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.
↵# A complete list of the principal investigators and participating institutions appears in the Appendix. The REDUCE study was supported by Knoll Ag. Ludwigshafen, Germany.
☆ This report was presented in part at the 45th Annual Scientific Session of the American College of Cardiology, Orlando, Florida, March 1996.
- Received March 26, 1996.
- Revision received July 11, 1996.
- Accepted July 17, 1996.