Editorial An Aspirin a Day to Keep the Clots Away Can Aspirin Prevent Recurrent Thrombosis in Extended Treatment for Venous Thromboembolism? Thomas W. Wakefield, MD; Andrea T. Obi, MD; Peter K. Henke, MD


atients presenting with deep vein thrombosis (DVT) in the absence of any identifiable risk factors are said to have an unprovoked or idiopathic DVT. Recurrent events are much more common in these patients (10% versus ≤ 3% at 1 year) compared with patients with a DVT provoked by a reversible risk factor, and such events represent a major healthcare problem.1 Three months of anticoagulation is sufficient to decrease the risk of recurrent thrombosis related to the initial DVT. However, once therapy is discontinued, the risk for recurrence rises dramatically. It has been suggested that 30% to 50% of patients experience a recurrence at 10 years.2,3 Factors associated with a higher likelihood of recurrence are male sex, elevated D dimer, incomplete resolution of DVT, body mass index ≥30, and post-thrombotic syndrome.4 In fact, a number of tools have been developed to determine the risk of recurrence after DVT.

Article see p 1062 In the current management paradigm, patients with unprovoked DVT are evaluated for long-term anticoagulation after initial treatment with 3 to 6 months of anticoagulation. The risks of major bleeding during prolonged therapy are periodically weighed against the benefits of continuing anticoagulation in high-risk patients. Data supporting this approach come from 4 studies demonstrating a decrease in recurrent venous thromboembolism (VTE) by 90% with extended conventional dose vitamin K antagonists (VKA) therapy.5 Major bleeding occurs in 20 per 1000 patients, and as of yet no validated prediction tool exists to predict risk–benefit ratio of extended therapy.6 Factors associated with an increased risk of bleeding include advanced age >75 years, history of gastrointestinal bleeding, noncardioembolic stroke, renal or hepatic disease, concomitant antiplatelet usage, and poor control of anticoagulation.5 In the interest of diminishing the bleeding risk while conferring protection against recurrent venous thromboembolism several approaches have been taken: subtherapeutic anticoagulation with VKA, new oral anticoagulant agents, and aspirin.7 Two trials randomized patients after completing fully VKA anticoagulation (3–6 months) to either placebo or sub The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the University of Michigan, Ann Arbor, MI. Correspondence to Thomas W. Wakefield, MD, University of Michigan, CVC 5463, 1500 E. Medical Center Drive SPC 5867, Ann Arbor, MI 48109-5867. E-mail [email protected] (Circulation. 2014;130:1031-1033.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.114.012235

therapeutic VKA therapy (target international normalized ratio of 1.5–1.9). Patients receiving indefinite sub therapeutic anticoagulation had a 62% to 64% relative risk reduction of recurrent VTE.7,8 Although low-intensity VKA was more effective than placebo, it was less efficacious than full-dose VKA. Use of a lower international normalized ratio target did not decrease the number of clinically important bleeding events, dampening overall enthusiasm for this approach.8 New oral anticoagulants (NOACs) which do not require monitoring nor dosage adjustment have emerged as a convenient alternative for long-term prevention of recurrent VTE. To date, 3 trials have evaluated NOACs against placebo for an additional 12 months of therapy beyond initial anticoagulation9–11 (Table). In a pooled meta-analysis of the data, NOACs decreased the risk of recurrent VTE or VTE-related death by 84% with a number needed to treat of 17 compared with placebo.12 However, bleeding remained a significant source of morbidity with a higher risk of major or clinically relevant bleeding (4.6% versus 2.0%; odds ratio, 2.69; 95% confidence interval, 1.25–5.77) in the NOAC group and a number needed to harm of 39.12 One trial has evaluated dabigatran compared with warfarin for the extended treatment of VTE. In this trial, patients were randomized to either dabigatran 150 mg twice daily or warfarin (with a goal international normalized ratio of 2.0–3.0) for 12 months after completion of acute anticoagulation. The primary end point of symptomatic DVT, fatal pulmonary embolism, and all-cause mortality was similar between the 2 groups. A lesser risk of major bleeding (5.6% versus 10.2%, P1 episode of venous thrombosis. ASA indicates aspirin; and VTE, venous thromboembolism.

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Wakefield et al   Prevention of Recurrent Venous Thromboembolism   1033 contraceptives), is taking 1 aspirin per day at the end of a full course of anticoagulation beneficial? 4. Will other medications such as statins synergize with aspirin to reduce the incidence of recurrent VTE? 5. Will the more potent antiplatelet theinopyridines be more or less effective than aspirin? 6. Because patients with cancer represented only a small proportion of patients and patients with coronary artery disease were excluded, what are the recommendations in these groups of patients? 7. Finally, will the current data on only a little >1200 patients hold up in day to day clinical use? As is the case with all good studies, more questions remain to be answered and are the seeds for future studies.

Disclosures None.

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An Aspirin a Day to Keep the Clots Away: Can Aspirin Prevent Recurrent Thrombosis in Extended Treatment for Venous Thromboembolism? Thomas W. Wakefield, Andrea T. Obi and Peter K. Henke Circulation. 2014;130:1031-1033; originally published online August 25, 2014; doi: 10.1161/CIRCULATIONAHA.114.012235 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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An aspirin a day to keep the clots away: can aspirin prevent recurrent thrombosis in extended treatment for venous thromboembolism?

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