*Mixed* promising results???
Wednesday November 14, 4:36 pm Eastern Time
Press Release
SOURCE: Universiteit Erasmus Rotterdam
Study Shows Promising Results for Fondaparinux in The Treatment of Unstable Angina
After Positive Clinical Findings in the Prophylaxis and Treatment Of Venous Thromboembolism and in Acute MI, Findings of Phase IIb Study Show Promise for Fondaparinux in Acute Coronary Syndrome
ROTTERDAM, The Netherlands, Nov. 14 /PRNewswire/ -- The results of the phase IIb PENTUA study comparing fondaparinux -- fondaparinux is the first of a new class of selective synthetic factor Xa inhibitors -- to the low molecular weight heparin enoxaparin in the treatment of patients with acute coronary syndrome, were announced today at the Scientific Sessions 2001 of the American Heart Association in Anaheim, California. There was no clear dose-response relationship observed for fondaparinux in terms of efficacy and safety. The study demonstrated that fondaparinux was at least as effective and safe as enoxaparin.
``We are intrigued with these results, which show that the selective and potent inhibition of Factor Xa induced by fondaparinux could improve the treatment of acute coronary syndrome,'' said Professor M.L. Simoons from Erasmus University, principal investigator of the study. ``Since acute coronary disease remains a major medical emergency, these promising findings of the PENTUA study indicate that fondaparinux deserves further investigation in this setting.''
PENTUA is a double blind, randomized, controlled, dose-ranging study of more than 1,100 patients enrolled in 66 centers in 5 countries. The overall objective of the study was to assess and compare the safety and efficacy of four different dose levels of fondaparinux (ranging from 2.5 to 12 mg once daily subcutaneous) and a fixed dose regimen of enoxaparin (1 mg/kg body weight, administered subcutaneously twice daily) in patients with unstable angina. Patients enrolled in the study had angina at rest or during minimal exertion in whom the onset of the last episode of pain was less than 24 hours before the start of the screening ECG or suspected or documented myocardial infarction (MI) without persistent ST-segment elevation.
Fondaparinux blocks the coagulation cascade through the selective inhibition of Factor Xa, resulting in the prevention of thrombin formation. In addition to the blockage of the coagulation cascade, it can potentiate the blockade of platelet aggregation, as achieved with an antiplatelet regimen, which could explain the positive findings demonstrated both in models of arterial thrombosis and now in the PENTUA study.
``The PENTUA study showed promising albeit preliminary overall results for fondaparinux in patients with acute coronary disease. The selection of doses for further clinical investigation will have to take into account additional analyses of the PENTUA study findings, as well as those of other trials conducted with fondaparinux in this setting,'' said Professor Simoons.
These interesting phase II findings with fondaparinux in acute coronary syndrome follow the results recently obtained in a broad phase III clinical trial program which evaluated fondaparinux in the prophylaxis of venous thromboembolism in more than 7,000 patients undergoing orthopedic surgery.
Summary of the PENTUA study.
Maarten L. Simoons, Thoraxcenter, Rotterdam, The Netherlands, on behalf of PENTUA Investigators.
Objectives
To assess in patients with acute coronary syndromes, with ST-segment elevation; the dose-response relation of 4 dose levels (fondaparinux (2.5, 4, 8, 12 mg, once daily)) in comparison with enoxaparin (1 mg/kg/BID twice daily), with respect to the occurrence of death, myocardial infarction and recurrent ischemia as well as with respect to safety (bleeding).
Methods/patients
1147 patients were enrolled in 66 hospitals in 5 European countries. Data were complete, including > 12 hours continuous 12 lead ECG recording, and without protocol violation in 929 patients. Male 67%, age 83 years (24 - 89), ECG abnormalities at enrollment 80%,m elevated cardiac troponin 41%.
Results
Results (%) Fondaparinux Enoxaparin
2.5 mg 4 mg 8 mg 12 mg 1 mg/kg/BID
Death, MI, Recurrent ischemia
Day 9 30.0 43.5 41.0 34.8 40.2
Day 30 33.8 44.9 42.4 37.8 43.6
Major bleed 0.0 0.9 0.9 0.4 0.0
Major/
minor bleed 2.6 3.6 4.0 2.9 3.9
Conclusion
Overall, fondaparinux once daily is as effective and safe as enoxaparin twice daily in all doses tested. No clear dose-response was obtained. Results were consistent (data not shown) for different endpoint definitions, and different patient groups, including per protocol analysis (see above) and all patients randomized and treated. Best results were achieved with the lowest dose of fondaparinux (p<0.05 vs enoxaparin at day 9 and day 30). Further phase III studies of fondaparinux in patients with Acute Coronary Syndromes are warranted.
SOURCE: Universiteit Erasmus Rotterdam |
