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)

Aim To assess the benefit of short-term low molecular weightheparin nadroparin compared with unfractionated heparin in unstableangina or non-Q wave myocardial infraction patients and to determinewhether a longer, 2-week low molecular weight heparin regimenwould offer additional clinical benefit. Patients, Methods and Results This was a multicentre, prospective,randomized, double-blind study in three parallel groups, involving3468 patients. Patients received one of three treatment regimens:the unfractionated heparin group received an intravenous bolusof unfractionated heparin 5000IU, followed by an activated partialthromboplastin time adjusted infusion of unfractionated heparinfor 6±2 days; the nadroparin 6 group received an intravenousbolus of nadroparin 86 anti-Xa IU.kg^–1, followed by twicedaily subcutaneous injections of nadroparin 86 anti-Xa IU.kg^–1for6±2 days, and the nadroparin 14 group received an intravenousbolus of nadroparin 86 anti-Xa IU.kg^–1, followed by twicedaily subcutaneous injections of nadroparin 86 anti-Xa IU.kg^–1for14 days. No statistically significant differences were observedbetween the three treatment regimens with respect to the primaryoutcome (cardiac death, myocardial infarction, refractory angina,or recurrence of unstable angina at day 14). The absolute differencesbetween the groups in the incidence of the primary outcome were:–0·3% (P=0·85) for the nadroparin 6 groupvs 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 differencesregarding any of the secondary efficacy outcomes. However, therewas an increased risk of major haemorrhages in the nadroparin14 group compared with unfractionated heparin (3·5% vs1·6%;P=0·0035). Conclusions Treatment with nadroparin for 6±2 days providessimilar efficacy and safety to treatment with unfractionatedheparin, for the same period, in the therapeutic managementof 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.