Long-term risk of anticoagulant-related bleeding high in patients with first unprovoked VTE

There appears to be substantial long-term risks and consequences of anticoagulant-related major bleeding in patients with a first unprovoked venous thromboembolism (VTE), suggests a recent study.

The investigators searched the databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. They included randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months following completion of at least 3 months of initial anticoagulant treatment.

Two independent reviewers abstracted data and evaluated the quality of studies. In addition, unpublished data needed for analyses were obtained from the authors of the eligible studies.

Fourteen RCTs and 13 cohort studies, which included 9,982 patients who received a vitamin K antagonist (VKA) and 7,220 a direct oral anticoagulant (DOAC), were eligible for analysis. The incidence of major bleeding per 100 person-years was 1.74 events (95 percent confidence interval [CI], 1.34–2.20) with VKAs and 1.12 events (95 percent CI, 0.72–1.62) with DOACs, while the 5-year cumulative incidence of major bleeding was 6.3 percent (95 percent CI, 3.6–10.0) with VKAs.

The incidence of major bleeding among patients receiving either VKAs or DOACs was significantly higher among those aged >65 years or had a creatinine clearance <50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a haemoglobin level <100 g/L. Furthermore, the case-fatality rates of major bleeding with VKAs and DOACs were 8.3 percent (95 percent CI, 5.1–12.2) and 9.7 percent (95 percent CI, 3.2–19.2), respectively.

Of note, there were insufficient data to estimate the incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs.

“This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE,” the investigators said.