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Am Fam Physician. 2022;106(2):online

Clinical Question

What are the latest recommendations for anti-thrombotic therapy for patients with venous thromboembolism (VTE)?

Bottom Line

The guideline covers a lot of ground. Key updates include a clear preference for direct oral anti-coagulants, including in patients with cancer, and low-dose apixaban (Eliquis) or rivaroxaban (Xarelto) for extended-phase anticoagulation in patients with unprovoked VTE. There is greater leeway for observation only of selected patients with subsegmental pulmonary embolism (PE) or isolated distal lower extremity deep venous thrombosis (DVT), and outpatient treatment of selected patients with PE. (Level of Evidence = 1a)


The latest update to the American College of Chest Physicians guideline regarding antithrombotic therapy for VTE adds four new recommendations and updates eight others. The authors identified an initiation phase when anticoagulants are first given, a treatment phase of three months, and an extended phase for selected patients beyond three months. For patients with acute isolated distal DVT, the guidelines recommend two weeks of serial imaging, with anticoagulation only if the DVT extends or the patient has severe symptoms or risk factors for extension. For patients with subsegmental PE, no proximal DVT in the legs, and who are at low risk for recurrent VTE, clinical observation without anticoagulation is recommended. Outpatient therapy for PE is recommended if patients are clinically stable; there is no recent bleeding, thrombocytopenia, or severe liver or kidney disease; and they feel well enough to be treated at home and are likely to be adherent. For patients with asymptomatic PE incidentally diagnosed during computed tomography of the chest, anticoagulation is recommended because studies have shown a similar prognosis to symptomatic PE.

A direct oral anticoagulant (e.g., apixaban, dabigatran [Pradaxa], edoxaban [Savaysa], rivaroxaban) is recommended as first-line therapy. An exception should be made for patients with antiphospholipid syndrome, for whom warfarin (Coumadin) is recommended during the treatment phase. For patients with cancer, apixaban, edoxaban, and rivaroxaban are recommended over low-molecular-weight heparin for treatment of VTE. The authors make a weak recommendation for 45 days of fondaparinux (Arixtra), 2.5 mg daily, or rivaroxaban, 10 mg daily, for patients with superficial venous thrombosis of the lower leg. Extended-phase low-dose anticoagulation with apixaban, 2.5 mg twice daily, or rivaroxaban, 10 mg once daily, is recommended for all patients with unprovoked VTE. This has only been studied for two to four years, so extending anticoagulation beyond that is of uncertain benefit. Aspirin is recommended when patients discontinue extended-phase anticoagulation.

For patients with PE, thrombolytics are recommended only for patients with hypotension initially or who deteriorate clinically, assuming they do not have high bleeding risk. For those with a high bleeding risk or for those whom thrombolysis was ineffective, catheter-assisted thrombus removal is recommended. Inferior vena cava filters are recommended only for patients with DVT who have a contraindication to anticoagulation. For patients with cerebral vein or venous sinus thrombosis, anticoagulation is recommended. Compression stockings are not recommended for patients with acute DVT.

Study design: Practice guideline

Funding source: Foundation

Setting: Various

Reference: Stevens SM, Woller SC, Kreuziger LB, et al. Executive summary: antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest. 2021;160(6):2247-2259.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.

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