Discontinuing anticoagulation due to bleeding raised 5-year major bleeding risk to 15% vs 5.8% (aSHR 3.48) and all-cause death to 56% vs 21% (aHR 1.66), with no recurrent VTE difference.
Does discontinuing anticoagulation due to bleeding events affect the risk of recurrent VTE, major bleeding, and all-cause death compared to non-bleeding reasons in patients with VTE?
In patients with VTE, discontinuing anticoagulation due to bleeding events is associated with increased subsequent major bleeding and mortality, but not recurrent VTE, compared to non-bleeding reasons.
Abstract Background/Introduction The current guidelines recommend extended anticoagulation therapy for patients who are not at low risk of recurrent venous thromboembolism (VTE). Nevertheless, anticoagulation therapy is discontinued in some of these patients partly due to bleeding events. However, there have been scarce data on how reasons for discontinuing anticoagulation therapy affect clinical outcomes after discontinuation. Purpose The present study aimed to evaluate impact of reasons for discontinuing anticoagulation therapy on clinical outcomes after discontinuation in patients with VTE, using a large-scale observational database. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 1511 patients with VTE who received anticoagulation therapy beyond 30 days and subsequently discontinued anticoagulation therapy. The eligible patients were divided into discontinuation due to bleeding events and discontinuation due to non-bleeding reasons groups. The primary outcome was recurrent VTE after discontinuation and secondary outcomes were major bleeding and all-cause death after discontinuation. We used competing risk methods considering all-cause death as a competing risk. Results In the present study population, 107 patients (7.1%) discontinued anticoagulation due to bleeding events and 1404 (93%) due to non-bleeding reasons. The bleeding group tended to be older, underweight, and more likely to have comorbidities such as atrial fibrillation, chronic lung disease, active cancer, anemia, thrombocytopenia, and renal dysfunction than the non-bleeding group. There was no significant difference in the cumulative 5-year incidence of recurrent VTE between the groups (bleeding group: 9.8% versus non-bleeding group: 12%, P=0.60) (Figure 1). The cumulative 5-year incidences of major bleeding and all-cause death were higher in the bleeding group than in the non-bleeding group (major bleeding: 15% versus 5.8%, P0.001; and all-cause death: 56% versus 21%, P0.001) (Figure 2). Even after adjusting for the confounders, the risk of recurrent VTE, major bleeding and all-cause death showed consistent results with the unadjusted results (recurrent VTE: adjusted subhazard ratio aSHR, 1.02; 95%CI, 0.50-2.07, P=0.96; major bleeding: aSHR, 3.48; 95%CI, 1.73-6.98, P0.001; all-cause death: aHR, 1.66; 95%CI, 1.21-2.27, P=0.002). Conclusions The risk of recurrent VTE after discontinuing anticoagulation therapy did not significantly differ irrespective of discontinuation due to bleeding events or non-bleeding reasons; however, the risk of major bleeding was significantly higher in patients with discontinuation due to bleeding events. These findings might suggest the importance of bleeding rather than thrombotic risk in patients with discontinuation due to bleeding events.Figure 1 Figure 2
Nishimoto et al. (2025) studied this question. Discontinuing anticoagulation due to bleeding raised 5-year major bleeding risk to 15% vs 5.8% (aSHR 3.48) and all-cause death to 56% vs 21% (aHR 1.66), with no recurrent VTE difference.