Aspirin for the Prevention of Recurrent Venous Thromboembolism: The INSPIRE Collaboration

Study Questions:

How effective is low-dose aspirin at preventing recurrent venous thromboembolism (VTE)?


An a priori, individual-patient data analysis of two trials was undertaken in patients with a first episode of unprovoked VTE who had completed initial anticoagulation therapy and then were randomized to low-dose aspirin (100 mg) or placebo. Outcomes assessed included recurrent VTE, arterial ischemic events (myocardial infarction and stroke), bleeding, and death. Net clinical benefit, defined as the combined symptomatic VTE, myocardial infarction, stroke, all-cause mortality, and major bleeding, was calculated.


A combined 1,224 patients were followed for a median 30.4 months. During the follow-up, recurrent VTE occurred in 112/608 (18.4% or 7.5% per year) patients who received placebo compared to 81/616 (13.1% or 5.1% per year) patients who received aspirin (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90). After adjustment for treatment adherence (11.4-13.4% per year study drug discontinuation rate), recurrent VTE was reduced in patients who took aspirin (HR, 0.58; 95% CI, 0.40-0.85). Clinically relevant bleeding occurred in 12 patients (0.7% per year) assigned to the placebo arm and 19 patients (1.1% per year) assigned to the aspirin arm. Net clinical benefit was improved from 9.8% per year to 6.5% per year (HR, 0.67; 95% CI, 0.52-0.86) in patients randomized to aspirin compared to placebo.


The authors concluded that aspirin therapy, after an initial course of anticoagulation, significantly reduces the risk of VTE recurrence in patients with a first unprovoked VTE. The authors also concluded that aspirin therapy is not associated with a significantly increased risk of bleeding.


Since patients with a first unprovoked VTE are at risk for VTE recurrence (up to 25% over 5 years), efforts to reduce the risk of recurrence are critically important. While the finding of this prespecified meta-analysis of the WARFASA and ASPIRE trials are not surprising, the increased sample size allows for better treatment effect estimates. Clinicians can take comfort in knowing that use of low-dose aspirin likely has a significant ability to prevent recurrent VTE without a significantly increased risk of bleeding. However, clinicians need to remember that use of systemic anticoagulation with warfarin or a newer target-specific oral anticoagulant has been shown to be approximately twice as effective as low-dose aspirin for preventing recurrent VTE. It is important that clinicians assess a patient’s risk for recurrence and engage patients in a shared decision-making process to determine the most appropriate agent for VTE prevention.

Clinical Topics: Anticoagulation Management, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Myocardial Infarction, Stroke, Warfarin, Venous Thromboembolism

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