Clinical Question

Are direct oral anticoagulants better than conventional anticoagulants (e.g., warfarin) for the treatment of venous thromboembolism (VTE)?

Evidence-Based Answer

Direct oral anticoagulants are as effective as conventional anticoagulants at preventing recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE) and reducing all-cause mortality. Direct oral anticoagulants slightly decrease the likelihood of major bleeding compared with conventional anticoagulants in the treatment of VTE (number needed to treat [NNT] = 123 for direct thrombin inhibitors; NNT = 156 for oral factor Xa inhibitors).^1,2 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

VTE is when a blood clot forms in a vein. The most common types are PE and DVT. An estimated 300,000 to 600,000 cases of PE occur annually in the United States.³ Due to the life-threatening nature of VTE, effective anticoagulation is essential for treatment and mortality reduction. Conventional therapy uses unfractionated heparin, low-molecular-weight heparin, fondaparinux, and vitamin K antagonists. More recently developed anticoagulants include two forms of direct oral anticoagulants: thrombin inhibitors and Xa inhibitors. Direct oral anticoagulants have several preferable characteristics compared with conventional therapy, including a more predictable effect, less frequent monitoring or redosing, and fewer drug interactions.⁴ The authors of these Cochrane reviews sought to assess the safety and effectiveness of direct oral anticoagulants vs. conventional therapies.

Two updated Cochrane reviews initially published in 2015 examined treatments for PE and DVT.^1,2 One Cochrane review examined therapeutic options for PE and included 10 randomized controlled trials (RCTs) with 13,073 patients.² The other Cochrane review was broader, examined treatments for DVT, and included 21 RCTs with 30,895 patients.¹ Every study from the Cochrane on PE treatment is included in the Cochrane on DVT treatment, except for one RCT that involved 114 patients.^1,2 Both reviews examined outcomes among patients treated with oral direct thrombin inhibitors (e.g., dabigatran [Pradaxa]) or oral factor Xa inhibitors (e.g., rivaroxaban [Xarelto], apixaban [Eliquis]), compared with patients treated with conventional anticoagulants. Studies that lasted at least three months and excluded intramuscular or intravenous anticoagulation were performed in multiple countries, including the United States. The primary outcomes examined were recurrent or new VTE. The secondary outcomes included all-cause mortality and adverse effects such as major bleeding.^1,2

There were no differences in recurrent VTE or all-cause mortality between direct oral anticoagulants and conventional anticoagulants in the treatment of DVT or PE. The rates for these outcomes were very low in each respective arm, estimating 3 to 30 outcomes per every 1,000 patients treated.

In the Cochrane review examining the treatment of patients with DVT, there was a difference in the risk of major bleeding events favoring oral direct thrombin inhibitors (odds ratio [OR] = 0.58; 95% CI, 0.38 to 0.89; number needed to harm [NNH] = 123) and oral factor Xa inhibitors (OR = 0.63; 95% CI, 0.45 to 0.89; NNH = 156) over conventional anticoagulants.¹ The Cochrane review describing the treatment of patients with PE found no difference in the risk of major bleeding.²

The 2021 CHEST guidelines recommend direct oral anticoagulants over conventional therapy in the general patient population.⁵ Direct oral anticoagulants are as effective as conventional therapies, may decrease major bleeding events, and should be considered first-line therapy for patients with VTE.^1,2

The practice recommendations in this activity are available at https://www.cochrane.org/CD010956 and https://www.cochrane.org/CD010957.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army, the U.S. Department of Defense, or the U.S. government.