Tuesday, March 14, 2006

What form of anticoagulation is best for unstable angina and NSTEMI?

The on line edition of NEJM has published, ahead of print, a large study by the OASIS-5 investigators comparing enoxaparin (Lovenox) and fondaparinux (Arixtra) in patients with non-ST segment elevation acute coronary syndromes (unstable angina and NSTEMI). Enoxaparin is a low molecular weight heparin. Fondaparinux is a synthetic pentasaccharide inhibitor of factor Xa. The primary efficacy endpoint was similar in the two groups but bleeding was markedly less in the fondaparinux group. Over all the number needed to treat with fondaparinux instead of enoxaparin to prevent 1 death was 150.

Of particular interest was how these agents were dosed compared to their doses for other indications. Fondaparinux showed non-inferiority despite a relatively low dose in comparison to enoxaparin. The low dose may explain the lower incidence of bleeding. Put another way: both agents are approved for both the prophylaxis and treatment of venous thromboembolism (VTE) with much higher doses for the treatment indication (two or more times the prophylactic dose). However in this study of acute coronary syndrome fondaparinux was administered in its VTE prophylactic dose while enoxaparin was given in its VTE treatment dose.

Both drugs are eliminated by renal excretion. For VTE indications enoxaparin’s labeling allows for dosage adjustment in renal failure whereas fondaparinux carries a contraindication for patients with creatinine clearance less than 30.

An accompanying editorial provides perspective.

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