The Medical Letter on Drugs and Therapeutics
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1433
New Oral Anticoagulants for Acute Venous Thromboembolism
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 Select a term to see related articles  Antithrombotics   apixaban   Arixtra   Coumadin   Deep vein thrombosis   DVT   edoxaban   Eliquis   Enoxaparin   Fondaparinux   Heparin   Lovenox   Pradaxa   Rivaroxaban   Venous thromboembolism   Warfarin   Xarelto dabigatran 

Anticoagulants are the drugs of choice for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively referred to as venous thromboembolism (VTE).

STANDARD TREATMENT — Patients with acute VTE are often treated initially with a parenteral anticoagulant such as unfractionated heparin, low molecular weight heparin (LMWH), or fondaparinux (Arixtra, and generics); all are associated with similar rates of mortality, recurrent VTE, and major bleeding. For most patients, the oral vitamin K antagonist warfarin (Coumadin, and others) is started on the same day as parenteral therapy and titrated to maintain an INR between 2 and 3. After ≥5 days, the parenteral anticoagulant is stopped and warfarin is continued as monotherapy, usually for at least 3 months.1

NEW ORAL ANTICOAGULANTS — Rivaroxaban (Xarelto), dabigatran etexilate (Pradaxa), apixaban (Eliquis), and edoxaban (not FDA-approved) have all been studied for treatment of acute VTE, but only rivaroxaban is FDA-approved for this indication. Unlike warfarin, the newer drugs do not require INR monitoring and have no dietary restrictions, but they have shorter half-lives (increasing the risks associated with missed doses) and no specific antidote to reverse their anticoagulant effect.

CLINICAL STUDIES — Only a small minority of patients in any clinical trial of a new oral anticoagulant for treatment of acute VTE were ≥75 years old, had a creatinine clearance (CrCl) <50 mL/min, or had cancer.

Rivaroxaban (Xarelto) A randomized open-label study (EINSTEIN) in 3449 patients compared rivaroxaban alone to standard therapy with the LMWH enoxaparin (Lovenox, and generics) plus a vitamin K antagonist for treatment of acute VTE. Rivaroxaban was non-inferior to standard therapy in reducing the rate of recurrent VTE. The rate of major or clinically relevant non-major bleeding, the primary safety endpoint, was the same in both groups.2 A second randomized open-label study (EINSTEIN-PE) in 4832 patients with PE found that rivaroxaban was non-inferior to enoxaparin plus a vitamin K antagonist in reducing the rate of recurrent VTE with a similar rate of major or clinically relevant nonmajor bleeding.3

Dabigatran etexilate (Pradaxa) A 6-month, randomized, double-blind trial (RE-COVER) in 2539 patients compared dabigatran to warfarin for treatment of acute VTE after initial treatment with a parenteral anticoagulant. Twice-daily dabigatran was non-inferior to warfarin in preventing recurrent VTE or VTE-related death, the primary efficacy endpoint. Rates of major bleeding were similar in the two groups.4

Apixaban (Eliquis) A 6-month, randomized, double-blind trial (AMPLIFY) in 5395 patients compared apixaban alone to enoxaparin plus warfarin for treatment of acute VTE. Twice-daily apixaban was non-inferior in preventing recurrent VTE or VTE-related death (the primary efficacy endpoint). Major bleeding, the primary safety outcome, occurred less frequently with apixaban (0.6% vs. 1.8%).5

Edoxaban – In a randomized, double-blind trial of 8240 patients with acute VTE first treated with unfractionated heparin or LMWH, once-daily edoxaban (not FDA-approved) was non-inferior to warfarin in preventing recurrent VTE or VTE-related death (the primary endpoint). Patients taking edoxaban had a significantly lower rate of major or clinically relevant non-major bleeding (8.5% vs. 10.3%).6

CONCLUSION — The new oral anticoagulants rivaroxaban (Xarelto), dabigatran etexilate (Pradaxa), and apixaban (Eliquis), and the investigational oral anticoagulant edoxaban all appear to be effective and safe for treatment of acute venous thromboembolism, but data in older and sicker patients are limited. They do not require INR monitoring and do not have dietary restrictions, but they have short half-lives that increase the risk of thrombosis with missed doses and no specific antidote to reverse their anticoagulant effect.

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