Antiplatelet Agents for the Treatment of Deep Venous Thrombosis

Is adding an antiplatelet agent for the treatment of deep venous thrombosis (DVT) safe and effective for preventing future complications?

Best medical practices for the initial treatment of uncomplicated DVT include anticoagulation, compression stockings, and physical exercise. In the management of DVT (both acute [i.e., treatment started within 21 days of symptom onset] and chronic [i.e., treatment started after 21 days of symptom onset]), adding an antiplatelet agent to standard practices does not show clear benefits or cause significant adverse effects.¹ (Strength of Recommendation: B, inconsistent or limited-quality patient-oriented evidence.)

After stroke and myocardial infarction, venous thromboembolism (VTE; includes pulmonary embolism [PE] and DVT) is the third most common cardiovascular disease diagnosed worldwide. The incidence of DVT (the most common VTE) is increasing with the aging population, and there are more than 100,000 PE-related deaths in the United States per year.²

Anticoagulation with direct oral anticoagulants, warfarin, or heparin is part of the standard initial treatment for DVT. Secondary treatment options include thrombolysis, mechanical thrombectomy, inferior vena cava filter, angioplasty, and stenting. Several studies have been done to assess whether adding antiplatelet agents to standard anticoagulation decreases the risk of recurrent VTE and mortality.

The Cochrane review included six randomized controlled trials (RCTs) with 1,625 adult participants from the United States, Canada, Europe, India, Argentina, Australia, and New Zealand.¹ Two groups were studied: participants with acute DVT and participants with chronic DVT. The length of treatment with antiplatelet agents varied from six months to two years. Treatment with antiplatelets varied from six to 24 months, but some studies presented follow-up data up to 37.2 months (exceeding treatment time). All studies used best medical practices or best medical practices plus placebo for comparison. Best medical practices were sometimes mentioned in the studies but were not comprehensively defined. Each comparison investigated the effects of antiplatelets on the recurrence of DVT, PE, mortality, and adverse effects. Four studies used various antiplatelet agents: dipyridamole; aspirin, 300 mg four times per day; sulfinpyrazone (Anturane), 800 mg per day; and indobufen (not available in the United States), 200 mg twice per day. Two trials used aspirin in a dosage of 100 mg per day. The authors considered all RCTs that used antiplatelet therapy at the same time as or after anticoagulation and analyzed the two groups separately.

There was no meta-analysis of patients treated with antiplatelet agents in acute DVT. Only one study addressed acute DVT, which yielded results of very low certainty.

The meta-analysis did not reveal a statistically significant benefit for the outcomes of mortality or progression to PE, and there was no increased risk of bleeding or other adverse effects in patients with chronic DVT who were receiving antiplatelet therapy. Use of antiplatelet therapy in addition to best practices decreased the risk of recurrent VTE compared with placebo (number needed to treat = 14; 95% Cl, 8 to 125; four studies; 901 participants). However, when only PE was studied, antiplatelet agents did not achieve a difference between the groups.

The 2021 CHEST guidelines from the American College of Chest Physicians for the management of VTE recommend the use of direct oral anticoagulants as first-line treatment for acute DVT or PE.³ For patients with VTE and otherwise stable cardiovascular disease, the CHEST guidelines suggest suspending aspirin therapy when initiating anticoagulation. The combination of anticoagulation plus aspirin does not seem to decrease mortality risk.

Editor's Note: The number needed to treat and related CI reported in this Cochrane for Clinicians were calculated by the authors based on raw data provided in the original Cochrane review.

The practice recommendations in this activity are available at https://www.cochrane.org/CD012369.