Clinical Question

Does aspirin reduce the likelihood of recurrent venous thromboembolism (VTE) when used after the discontinuation of anticoagulation?

Bottom Line

Aspirin improves long-term cardiovascular and thrombotic outcomes in patients who have had an initial unprovoked episode of VTE. The risk of bleeding was no higher in the aspirin group, perhaps because those at risk of bleeding were “uncovered” during the initial period of anticoagulation. (Level of Evidence = 1a)

Synopsis

This was an individual patient meta-analysis. In most meta-analyses, authors are limited to using published, aggregated data, but by combining data from different studies at the individual patient level, there is greater statistical power to detect important clinical effects. The authors of this report combined data from two previous trials: WARFASA with 403 patients and ASPIRE with 822 patients. The trials had similar designs and populations (nonpregnant adults with a first unprovoked deep venous thrombosis [DVT] or pulmonary embolism [PE]). There were 56 withdrawals from these studies before the end of the study period because of revoked consent (31), no qualifying VTE episode (12), and loss to follow-up (13). The WARFASA study followed patients for up to two years, and ASPIRE for up to four years.

The intervention in each study was aspirin, 100 mg, given once daily or matching placebo, and analysis was by intention to treat. The anticoagulation protocol was low-molecular-weight heparin (Lovenox) initially followed by warfarin (Coumadin) for most patients. The rate of recurrent VTE was approximately one-third lower in the aspirin group (5.1% vs. 7.5% per year; P = .008; number needed to treat [NNT] = 42 per year), with a similar hazard ratio of 0.66 for DVT and PE. The rate of myocardial infarction, stroke, or cardiovascular death was also lower (5.7% vs. 8.7% per year; P = .002; NNT = 33 per year), and there was no difference in the risk of major bleeding (0.4% per year in the placebo group vs. 0.5% in the aspirin group). The combined outcome of any adverse event (major vascular event, major bleeding, or death from any cause) was lower in the aspirin group as well (6.5% vs. 9.8% per year; P = .002; NNT = 30). The benefit of aspirin was greatest in the first year, but a consistent and significant benefit was seen in years 2 through 4.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Outpatient (any)

Reference: SimesJBecattiniCAgnelliGet alAspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation2014; 130( 13): 1062– 1071.