Low Molecular Weight Heparin (Reviparin) in Percutaneous Transluminal Coronary Angioplasty - REDUCE


REDUCE was a prospective, randomized, double-blind trial of the low molecular weight heparin (LMWH) reviparin versus unfractionated heparin (UFH) for prevention of adverse events and restenosis in patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA).


The LMWH reviparin will be associated with lower rates of restenosis and adverse events after PTCA compared with UFH. Cell culture data suggest an antiproliferative effect of LMWH that may translate into improved clinical endpoints.

Study Design

Study Design:

Patients Enrolled: 612
Mean Follow Up: 30 days
Mean Patient Age: 40-80
Female: 15

Patient Populations:

Patients scheduled to undergo single-vessel PTCA for stable or unstable angina (excluding Braunwald class 3C) who were suitable candidates for CABG


History of bleeding disorder, recent active bleeding, uncontrolled asthma or hypertension, active peptic ulcer disease, history of heparin-induced thrombocytopenia, acute MI within 14 days, or unstable angina requiring heparin therapy; also, left main coronary artery lesion <50% or PTCA of saphenous vein graft or prior PTCA at the same location

Primary Endpoints:

Major adverse events (death, MI, need for reintervention, or bypass surgery), loss of minimal luminal diameter, and incidence of restenosis over 30 days

Secondary Endpoints:

Bleeding complications

Drug/Procedures Used:

Patients scheduled to undergo single lesion PTCA for stable or unstable angina (excluding Braunwald class C) were randomized to either the LMWH reviparin (7000 IU) or UFH (10,000 IU) at the time of intervention. Standard balloon angioplasty was then performed from the transfemoral approach using an 8F guide catheter and standard techniques. Subsequently, all patients received an intravenous infusion of either UFH (24,0000 IU) or reviparin (10,5000 IU) over 16 hours.

After day 1, the UFH arm received daily placebo injections and the reviparin arm received the study drug at 3500 IU subcutaneously twice a day for 28 days. Repeat coronary angiography was performed at 26 ± 2 weeks after PTCA for all patients.

Concomitant Medications:

Aspirin (100 mg/day) was administered one day before and throughout the study period.

Principal Findings:

A total of 612 patients were enrolled in the trial; 306 to the UFH arm and 306 to the LMWH arm. At baseline, the groups were well matched in terms of age, gender, risk factors, angina class, and diseased vessel characteristics.

Using an intention to treat analysis, the combined endpoint of death, myocardial infarction (MI), coronary artery bypass grafting (CABG), or repeat PTCA at 30 days occurred in 32% of the UFH arm and 33.2% of the LMWH arm (relative risk 1.04, 95% confidence interval 0.83-1.31, p=0.707). Angiographic restenosis occurred in 34.4% of the UFH patients and 33% of the LMWH patients. Acute events immediately following PTCA (<1 day) occurred in 8.2% of the UFH arm and 3.2% of the LMWH arm.

This finding was largely due to an increased rate of rescue stent implantation in the UFH arm (6.9% vs. 2.0%, p=0.003). No significant differences occurred between groups for rates of bleeding complications.


Among patients with angina undergoing single-vessel PTCA, the LMWH reviparin was not associated with a significant difference in rates of major adverse events or restenosis compared to UFH. The antiproliferative effect of LMWH seen in cell culture studies did not translate into a clinical benefit in this trial. Although not a prespecified endpoint, REDUCE did demonstrate a reduction in early post-PTCA adverse events, suggesting LMWH may have a role immediately following angioplasty.


Karsch KR, Preisack MB, Baildon R, et al. Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial). Reduction of Restenosis After PTCA, Early Administration of Reviparin in a Double-Blind Unfractionated Heparin and Placebo-Controlled Evaluation. J Am Coll Cardiol 1996;28:1437-43.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Coronary Angiography, Heparin, Low-Molecular-Weight, Risk Factors, Confidence Intervals, Fibrinolytic Agents, Coronary Artery Bypass, Infusions, Intravenous, Angioplasty, Balloon, Coronary, Stents

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