Extended anticoagulant use for unprovoked VTE linked to ‘considerable’ bleeding risk

Patients who continued to use anticoagulant therapy beyond the initial 3 to 6 months of treatment for a first unprovoked venous thromboembolism were at “considerable” risk for major bleeding, researchers wrote.

“Venous thromboembolism (VTE) is a major contributor to the global burden of disease,” Faizan Khan, MSc, a PhD candidate in epidemiology at University of Ottawa, and colleagues wrote in Annals of Internal Medicine. “The annual incidence of acute VTE is one to two cases per 1,000 persons.”

Although physicians often suggest indefinite anticoagulant therapy after a first unprovoked VTE or weakly provoked VTE, the net clinical benefit of anticoagulant therapy beyond 3 to 6 months “is uncertain,” they wrote.

Khan and colleagues reviewed 14 randomized clinical trials and 13 cohort studies that analyzed adverse events among 17,202 patients with a first unprovoked VTE who received oral anticoagulant therapy for at least 6 additional months after completing a minimum of 3 months of initial anticoagulant treatment. Among the entire cohort, 9,982 patients received a vitamin K antagonist (VKA) and 7,220 received a direct oral anticoagulant (DOAC).

The researchers reported that the incidence of major bleeding for each 100 person-years was 1.74 events (95% CI, 1.34-2.2) with VKAs and 1.12 events (95% CI, 0.72-1.62) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (95% CI, 3.6-10).

“Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs,” Khan and colleagues wrote.

In addition, among patients who received either therapy, the incidence of major bleeding was statistically significantly higher among patients who were older than 65 years or had creatinine clearance of less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy or a hemoglobin level less than 100 g/L.

The case-fatality rate of major bleeding appeared to be similar with VKAs (8.3%; 95% CI, 5.1-12.2) and DOACs (9.7%; 95% CI, 3.2-19.2). This finding ran contrary to a previous meta-analysis of phase 3 randomized trials comparing DOACs (7.6%; 95% CI, 6.5-8.7) and VKAs (11%; 95% CI, 9.2-13.1) in patients with atrial fibrillation, according to the researchers.

“Findings from this study will help inform physician-patient discussions about long-term risks and consequences of anticoagulant-related major bleeding and help balance the net benefits and harms of extended anticoagulation to guide treatment duration for unprovoked VTE,” Kahn and colleagues wrote.