Tuesday April 11, 2006
Is Fondaparinux (arixtra) superior in Acute Coronary Syndromes ?
2 major studies published this week in The New England Journal of Medicine and JAMA regarding anticaogulation with Fondaparinux (arixtra) in Acute Coronary Syndromes.
NEJM: 20,078 patients with acute coronary syndromes were randomized either to receive fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days. The primary outcome were death, myocardial infarction, or refractory ischemia at nine days.The number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; But the rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent].Study concluded that Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity 1,2,3.
JAMA: Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12092 patients with STEMI from 41 countries. Patients were divided into 2 strata. 1. fondaparinux initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin is not indicated). 2. unfractionated heparin for up to 48 hours followed by placebo for up to 8 days. Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group. There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux), with significantly fewer cardiac tamponade (48 vs 28) with fondaparinux at 9 days. However, there was no benefit in those undergoing primary percutaneous coronary intervention. 4, 5.
Here one caution is important that fatal bleeding with Fondaparinux can be treated only with supportive treatment. Also half life of Fondaparinux is 17-21 hours. See related previous pearl LMWH and Antidot (protamine). 6
References: (click to get abstrat/article)
1. Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes - Volume 354:1464-1476, NEJM, April 6, 2006
2. Oasis 5 - clinicaltrials.gov
3. Therapy for Patients with Acute Coronary Syndromes - New Opportunities, Volume 354:1524-1527, NEJM April 6, 2006
4. Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial Infarction - JAMA. 2006;295:1519-1530. Vol. 295 No. 13, April 5, 2006
5. MICHELANGELO OASIS-6 : FOndaparinux in ST Elevation Myocardial Infarction
6. Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid. Neth J Med 2005 May;63(5):1846