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Publication Briefs

Review Suggests New Anticoagulants are Viable Option for Patients Receiving Long-Term Anticoagulation

Currently, vitamin K antagonists are the mainstay of treatment and prophylaxis of thromboembolism. In 2004, more than 30 million prescriptions for warfarin, the most common vitamin K antagonist, were written in the U.S. While warfarin significantly reduces the risk for thromboembolic complications, it has a narrow therapeutic window and requires continuous and regular monitoring. Recently, new oral anticoagulants (NOACs) have emerged within two drug classes: 1) factor Xa (FXa) inhibitors, and 2) direct thrombin inhibitors (DTIs). Although these NOACs have an advantage of predictable effect (eliminating the need for routine monitoring), their costs ($3,000/per year) are substantially higher than those of warfarin ($48/per year), excluding INR testing and provider visits for warfarin dose adjustment. VA recently commissioned a systematic review of the literature to evaluate newer anticoagulants compared with warfarin and venous thromboembolism.


  • New oral anticoagulants are a viable option for patients receiving long-term anticoagulation. DTIs and FXa inhibitors have the advantage of a more predictable anticoagulant effect, and fewer drug-drug interactions as well as equivalent or better mortality and vascular outcomes compared with warfarin. However, treatment benefits compared with warfarin are small and vary depending on the control achieved by warfarin treatment.
  • Six good quality randomized controlled trials comparing NOACs (2 DTI studies, 4 FXa inhibitor studies) with warfarin showed that in patients with AF, new oral anticoagulants decreased all-cause mortality. In patients with venous thromboembolism, new oral anticoagulants did not differ for mortality or outcomes.
  • Across indications, the risk of major and fatal bleeding was decreased with NOACs compared with warfarin. However, the bleeding risk with NOACs may be increased in individuals over the age of 75, and in those with renal impairment.
  • Sub-group analyses suggest a higher risk for myocardial infarction or acute coronary events with dabigatran (DTI) compared with FXa inhibitors.
  • Recent thromboprophylaxis guidelines conclude that patients with AF who are on good warfarin treatment control have little to gain by switching to dabigatran.


  • There were no head-to-head comparisons of NOACs and limited data on harms.

This study was funded by VA/HSR&D's Quality Enhancement Research Initiative (ESP Project 09-010). Authors are part of the VA Evidence-Based Synthesis Program in Durham, NC.

PubMed Logo Adam S, McDuffie J, Ortel T, and Williams J., Jr. Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Management of Atrial Fibrillation and Venous Thromboembolism. Annals of Internal Medicine August 28, 2012;Epub before print.

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