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Internal Medicine

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When Are Direct-Acting Oral Anticoagulants Not the Standard of Care?

Allan S. Brett, MD

In a unique review, experts discuss conditions for which warfarin or antiplatelet drugs are preferable to DOACs and conditions for which DOAC safety and efficacy is uncertain.

For most patients who require anticoagulation, direct-acting oral anticoagulants (DOACs) have so many advantages compared with warfarin that clinicians often no longer think about initiating warfarin. This shift in practice during the past decade certainly makes sense for anticoagulation in patients with venous thromboembolism or atrial fibrillation: Multiple large, randomized trials have confirmed that outcomes are equivalent or better with DOACs than with warfarin for those two indications — and DOAC therapy is much easier to manage.

However, for various other clinical conditions, the data supporting DOACs (instead of warfarin or antiplatelet therapy) are less compelling. Recently, a group of experts published a comprehensive, but very readable, review that classifies DOAC use into three general groups of disorders — those for which DOACs are preferred, those for which DOACs should not be used, and those for which the safety and efficacy of DOACs are uncertain (J Am Coll Cardiol 2024; 83:444. opens in new tab). This is the first published overview of DOACs organized in this way. Key points are as follows:

Conditions for which DOACs have proven efficacy and safety, and are the preferred agents:

  • Venous thromboembolism: All four available DOACs (i.e., apixaban, dabigatran, edoxaban, and rivaroxaban) are approved for this indication. One exception is thrombotic antiphospholipid syndrome (see below).

  • Atrial fibrillation (excluding patients with mechanical heart valves or rheumatic atrial fibrillation): All four DOACs are approved for stroke prevention in patients with atrial fibrillation. In addition, for patients with atrial fibrillation who have had recent acute coronary events or recent percutaneous coronary intervention, guidelines support use of a DOAC plus a single antiplatelet drug (usually clopidogrel).

Conditions for which DOACs are considered to be less efficacious or less safe, or to provide no benefit, compared with alternative antithrombotic agents

  • Mechanical heart valves: Warfarin is preferred.

  • Rheumatic atrial fibrillation: Warfarin is preferred.

  • Thrombotic antiphospholipid syndrome: Warfarin is preferred.

  • Transcatheter aortic valve replacement: Antiplatelet therapy is the standard treatment.

  • Embolic stroke of undetermined source: Antiplatelet therapy is the standard treatment.

Conditions for which efficacy and safety of DOACs are uncertain

  • Left ventricular thrombus, catheter-associated deep venous thrombosis, splanchnic vein thrombosis, and cerebral venous thrombosis: For each of these conditions, the authors discuss various nuances and complexities that should influence decisions on choice of antithrombotic therapy.

  • Pregnancy: The authors recommend against using DOACs for anticoagulation during pregnancy, also coumadin is contraindicated.

  • Patients with end-stage renal disease: The authors discuss the paucity of high-quality evidence for DOACs or warfarin; they cautiously note that dose-reduced DOACs can be considered — in the context of shared decision-making — when such patients have an indication for anticoagulation.

The review elaborates on each of the above bulleted points with both narrative discussion and easy-to-understand tables, illustrations, and algorithms. In addition, for readers with interest in pathophysiology, there is a short discussion of potential reasons why the effectiveness and safety of DOACs (which target factor Xa or thrombin) and warfarin (which inhibits the synthesis of multiple clotting factors) might differ across different clinical syndromes.


In addition, I recently learned that there is conflicting data in regards to the use of DOACs in patients with Type IV Pulmonary HTN (CTEPH) and that Warfarin is historically more commonly used and effective.

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