Aspirin appears to reduce recurrence of VTE after stopping anticoagulants

Aspirin reduced the risk of venous thromboembolism (VTE) recurrence with no apparent increase in major bleeding in patients who had an initial unprovoked VTE and had discontinued anticoagulant treatment, a study found.

Researchers conducted a multicenter, double-blind trial among patients with first-ever unprovoked proximal deep venous thrombosis, pulmonary embolism or both who had completed six to 18 months of oral anticoagulant treatment with a target international normalized ratio (INR) of 2.0 to 3.0. VTE was considered to be unprovoked when it occurred in the absence of any known risk factor.

More than 400 patients were randomized to aspirin, 100 mg once daily, or placebo for two years. Randomization occurred within two weeks after vitamin K antagonists had been withdrawn. The primary efficacy outcome was recurrence of VTE, and the primary safety outcome was major bleeding.

An overt bleeding event was defined as major if it was fatal, if it occurred in a critical location (intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or intramuscular [leading to a compartment syndrome]), or if it was associated with a decrease in hemoglobin level of at least 2.0 g/dL or required a transfusion of two or more units of whole blood or red cells. Clinically relevant, nonmajor bleeding was defined as any overt bleeding that required a medical intervention and did not meet any of the criteria for major bleeding.

Study results appeared in the May 24 New England Journal of Medicine.

From May 2004 through August 2010, VTE recurred in 71 patients (8.6% patients per year). Recurrent VTE was due to deep venous thrombosis in 44 patients (ipsilateral in 51% of cases) and to pulmonary embolism in 27 patients (fatal in 2 patients). In 77% of cases, recurrence took place in the absence of any known risk factor for VTE.

A recurrence in the form of pulmonary embolism was more common among patients who entered the study because of prior pulmonary embolism than among those who entered because of deep venous thrombosis (12.7% vs. 3.2%; hazard ratio, 5.52; 95% CI, 2.29 to 13.30; P<0.001).

Overall, VTE recurred in 28 of the 205 patients who received aspirin, as compared with 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% CI, 0.36 to 0.93; P=0.02)

Over a median treatment period of 23.9 months, while taking the study drug, 23 patients in the aspirin group had a recurrence, as compared with 39 patients in the placebo group (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92; P=0.02). Eleven of 83 patients in the aspirin group who entered the study because of pulmonary embolism had a recurrent event, as compared with 16 of 67 patients in the placebo group (6.7% vs. 13.5% per year; hazard ratio, 0.38; 95% CI, 0.17 to 0.88; P=0.02).

Among the patients who entered the study because of deep venous thrombosis, 17 of 122 in the aspirin group and 27 of 130 in the placebo group had a recurrent event (6.5% and 10.2% per year, respectively; hazard ratio, 0.65; 95% CI, 0.65 to 1.20; P=0.17).

Two episodes of nonfatal major bleeding occurred in the study, one in the placebo group (gastric ulcer) and one in the aspirin group (bowel angiodysplasia). Three patients in the aspirin group and three patients in the placebo group developed clinically relevant nonmajor bleeding (gingival bleeding and two cases of cutaneous hematomas in the aspirin group, hemorrhagic gastritis and two cases of musculoskeletal bleeding post-trauma in the placebo group). Five patients developed an adverse event that was attributed to the study drug and led to treatment withdrawal: gastric pain in three patients (two in the placebo group, one in the aspirin group), a cutaneous reaction in one patient (aspirin group), and renal failure in one patient (aspirin group).

The authors concluded that in patients with unprovoked VTE, aspirin therapy, begun after six to 18 months of oral anticoagulant treatment, reduced the rate of recurrence by about 40%, as compared with placebo. “This benefit is achieved with no apparent increase in the risk of major bleeding,” they wrote.