In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral. 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.

Results Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11. Ballast Tray Design Manual Bulletin No 49001. 0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups. The risk of recurrence of venous thromboembolism persists for many years after anticoagulant treatment is withdrawn.

This risk is particularly high among patients with unprovoked venous thromboembolism, about 20% of whom have a recurrence within 2 years after treatment with vitamin K antagonists has been discontinued. Extending treatment with these agents reduces the risk of recurrence but is associated with an increased risk of bleeding, as well as the inconvenience and expense of laboratory monitoring and dose adjustments. The role of aspirin in the primary prevention of venous thromboembolism has been evaluated in various clinical settings. In these studies, aspirin was associated with a risk reduction ranging from 20 to 50%. A potential benefit from antiplatelet therapy in the secondary prevention of venous thromboembolism first became evident with the results of a randomized study involving only 39 patients. The aim of the Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) study was to assess the clinical benefit of aspirin for the prevention of recurrence after a course of treatment with vitamin K antagonists in patients with unprovoked venous thromboembolism. Patients Patients older than 18 years of age were eligible for the study if they had been treated for 6 to 18 months with vitamin K antagonists (with a target international normalized ratio [INR] of 2.0 to 3.0) for first-ever, objectively confirmed, symptomatic, unprovoked proximal deep-vein thrombosis, pulmonary embolism, or both.

Venous thromboembolism was considered to be unprovoked when it occurred in the absence of any known risk factor for this event. The main exclusion criteria can be found in the, available with the full text of this article at NEJM.org.

Outcome Measures All suspected study outcome events were assessed by a central, independent adjudication committee whose members were unaware of the group assignments and who reviewed the imaging results. The primary efficacy outcome was symptomatic, objectively confirmed recurrence of venous thromboembolism, defined as the composite of deep-vein thrombosis or nonfatal or fatal pulmonary embolism. (Criteria for the diagnosis of recurrence are provided in the.) Pulmonary embolism was considered to be the cause of death if it was confirmed on autopsy or if death was preceded by a diagnosis of either pulmonary embolism (objectively confirmed on computed tomography or lung scanning) or deep-vein thrombosis (objectively confirmed on compression ultrasonography) and whenever the cause could not be attributed to an alternative diagnosis. Deaths were classified as being due to pulmonary embolism, bleeding, or other causes.

Secondary efficacy outcomes included nonfatal myocardial infarction, unstable angina, stroke, transient ischemic attack, acute ischemia of the lower limbs, and death from any cause. The principal safety outcome was major bleeding. An overt bleeding event was defined as major if it was fatal, occurred in a critical location (intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or intramuscular [leading to a compartment syndrome]), or was associated with a decrease in the hemoglobin level of at least 2.0 g per deciliter or required a transfusion of 2 or more units of whole blood or red cells. Clinically relevant, nonmajor bleeding, defined as any overt bleeding that required a medical intervention and did not meet any of the criteria for major bleeding, was a secondary safety outcome. Study Oversight The study was designed by the members of the steering committee. Data were collected, maintained, and analyzed by the Clinical Research Unit of the University of Perugia, Italy. The protocol and amendments were approved by the institutional review board or ethics committee at each study center.