By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
Patients with unprovoked venous thromboembolism (VTE) are at high risk of recurrence after discontinuation of vitamin K antagonist (such as warfarin) therapy, with an approximately 10% risk of recurrence within the first year and 5% risk per year thereafter.1-6 Extending treatment with warfarin or similar agents reduces the risk of recurrence while treatment continues,1-7 but such therapy is, of course, associated with an increased risk of bleeding and the inconvenience of laboratory monitoring and dose adjustment.8 Several studies have evaluated the efficacy of the new oral anticoagulants for the prevention of recurrent VTE as part of the initial or the extended treatment regimen, but these drugs still carry a risk of bleeding and are expensive.9-14 Therefore, aspirin, as a low-cost and relatively safe drug, was recently evaluated in the Aspirin for the Prevention of Recurrent Venous Thromboembolism (WARFASA)15 and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials.16 These trials demonstrated that aspirin reduced the risk of recurrent VTE, but they were not sufficiently powered to detect moderate treatment effects for particular outcomes or subgroups.
Simes and associates performed an analysis of the two trials15-16 in order to more accurately estimate the effects of aspirin therapy overall, on individual outcomes, and in prespecified subgroups of patients.17 The major bleeding rate was low for both the placebo group and for the aspirin-treated group, and aspirin was found to reduce VTE by 42% in the broad cross-section of patients with a first unprovoked VTE.
COMMENTARY
Fewer than 50% of the patients in the United States and around the world with unprovoked VTE are routinely treated with long-term anticoagulant therapy.18–20 The prospectively planned analysis of the WARFASA and ASPIRE trials using individual patient data provides strong evidence that in patients with a prior unprovoked VTE, aspirin, after any initial anticoagulation therapy had been completed, was effective in reducing the rate of VTE recurrence. It has been estimated that there are 1 million patients worldwide with unprovoked VTE and that if they were to remain on aspirin therapy long term, 100,000 events might be prevented with only a minimal increase in bleeding. Besides being cost-effective, more importantly, aspirin therapy in this group of patients is medically effective and should be continued long term.
In summary, the prospective combined analysis of the WARFASA and ASPIRE trials provides clear evidence that long-term aspirin therapy reduces the risk of recurrent VTE events by approximately 40% and is both very safe and effective. Even though it does not reduce the rate of recurrent VTE as much as warfarin or the newer oral anticoagulants, among patients for whom these therapies are not considered appropriate or have been discontinued for any reason, aspirin therapy should be strongly considered.
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J Thromb Haemost 2013;11(suppl 2):84.
