FRAXiparine in Ischemic Syndrome (1999)


Treatment of unstable angina or non-Q wave myocardial infarction

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To assess the benefit of nadroparin compared with UFH in patients with unstable angina or non-Q wave myocardial infarction and to determine whe­ther a prolonged nadroparin regimen would offer additional clinical benefit

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Trial design

Prospective, randomized, double-blind study with parallel groups
Active treatment: nadroparin 86 anti-Xa IU/kg i.v. bolus, followed by 86 anti-Xa IU/kg s.c. twice daily for 6±2 days (n=1666) or for 14 days; UFH placebo (n=1151)
Control treatment: UFH 5000 IU i.v. bolus, followed by an infusion of 1250 IU/h (titrated according to aPTT) for 6±2 days; nadroparin placebo (n=1151)

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Primary efficacy endpoint: composite of cardiac death, myocardial infarction, refractory angina, or recurrence of unstable angina at day 14
Secondary efficacy endpoint: combined efficacy outcome at 6 days and 3 months; occurrence of individual outcomes (cardiac death, death from any cause, myocardial infarction, refractory angina, recurrent angina, emergency or planned PTCA or CABG); composite of all-cause death and myocardial infarction, at day 6, day 14 and month 3
Safety endpoint: major hemorrhage, severe thrombocytopenia and other serious adverse events at days 6 and 14

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Trial participants

3468 patients (mean age 64 years) admitted with characteristic anginal pain within the 48 hours prior to inclusion or non-Q wave myocardial infarction, defined as ST-segment depression

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Efficacy outcome: The intention-to-treat population included 3457 patients. At day 14, the primary composite endpoint occurred in 207 of 1151 patients (18.1%) in the UFH group, 207 of 166 patients (17.8%) treated 6 days with nadroparin and in 230 of 1151 patients (20.0%) treated 14 days with nadroparin. The differences between the groups were not statistically significant. Furthermore, there were no significant intergroup differences regarding any of the secondary efficacy outcomes at day 14. At 3 months, a 4% absolute increase in the occurrence of the combined efficacy outcome was observed in the nadroparin 14 group compared with the UFH group, mainly due to an excess of recurrent angina (p=0.03)
Safety outcome: At 14 days, there was an increased risk of major hemorrhages in the nadroparin 14 group: 3.5% compared with 1.6% in the UFH group 1.5% in the nadroparin 6 group

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Efficacy: The short-term treatment with nadroparin was as effective as the treatment with UFH. Prolonged nadroparin treatment provides no additional clinical benefit
Safety: Prolonged nadroparin treatment was associated with an increase of major bleeding events

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FRAX.I.S. Study Group. 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). Eur Heart J 1999;20:1553-1562

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Corresponding author

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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