Copyright © 1999 by the European Society of Cardiology.
Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome)
revised July 26, 1999; accepted July 26, 1999
Abstract
Aim To assess the benefit of short-term low molecular weight heparin nadroparin compared with unfractionated heparin in unstable angina or non-Q wave myocardial infraction patients and to determine whether a longer, 2-week low molecular weight heparin regimen would offer additional clinical benefit.
Patients, Methods and Results This was a multicentre, prospective, randomized, double-blind study in three parallel groups, involving 3468 patients. Patients received one of three treatment regimens: the unfractionated heparin group received an intravenous bolus of unfractionated heparin 5000IU, followed by an activated partial thromboplastin time adjusted infusion of unfractionated heparin for 6±2 days; the nadroparin 6 group received an intravenous bolus of nadroparin 86 anti-Xa IU.kg–1, followed by twice daily subcutaneous injections of nadroparin 86 anti-Xa IU.kg–1for 6±2 days, and the nadroparin 14 group received an intravenous bolus of nadroparin 86 anti-Xa IU.kg–1, followed by twice daily subcutaneous injections of nadroparin 86 anti-Xa IU.kg–1for 14 days. No statistically significant differences were observed between the three treatment regimens with respect to the primary outcome (cardiac death, myocardial infarction, refractory angina, or recurrence of unstable angina at day 14). The absolute differences between the groups in the incidence of the primary outcome were: –0·3% (P=0·85) for the nadroparin 6 group vs the unfractionated heparin group and +1·9% (P=0·24) for the nadroparin 14 group vs the unfractionated heparin group. Furthermore, there were no significant intergroup differences regarding any of the secondary efficacy outcomes. However, there was an increased risk of major haemorrhages in the nadroparin 14 group compared with unfractionated heparin (3·5% vs 1·6%;P=0·0035).
Conclusions Treatment with nadroparin for 6±2 days provides similar efficacy and safety to treatment with unfractionated heparin, for the same period, in the therapeutic management of acute unstable angina or non-Q wave myocardial infarction, and may be easier to administer. A prolonged regimen of nadroparin (14 days) does not provide any additional clinical benefit.
Key Words: unstable angina, randomized clinical trial, unfractionated heparin, low molecular weight heparin
f1 Correspondence: Alain Leizorovicz, MD, Clinical Pharmacology Unit, EA 643, Faculté RTH Laënnec, Rue Guillaume Paradin, BP 8071, 69376 Lyon, Cedex 08, France.
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