Effectiveness and Safety of Direct Oral Anticoagulants Among Octogenarians with Venous Thromboembolism: An International Multidatabase Cohort Study

Background: The effects of direct oral anticoagulants (DOACs) among octogenarian patients with venous thromboembolism remains poorly understood. To address this knowledge gap, our study aimed to assess the effectiveness and safety of DOACs compared to vitamin K antagonists (VKAs) among octogenarians with venous thromboembolism.

Methods: We conducted an international cohort study using administrative health care databases from Québec, Canada, and Germany. We assembled 2 population-based cohorts of octogenarians with incident venous thromboembolism initiating treatment with DOACs or VKAs. The study period spanned from January 2012 to the most recent date of data availability (Québec: December 2016; Germany: December 2019). Using an as-treated exposure definition, we compared use of DOACs to use of VKAs, applying inverse probability of treatment weighting based on high-dimensional propensity scores to balance exposure groups. Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of recurrent venous thromboembolism, major bleeding, and all-cause mortality. The results were meta-analyzed using random-effects models.

Results: Overall, our study included 6737 octogenarians with venous thromboembolism (Québec: n = 2556; Germany: n = 4181) who initiated use of DOACs (n = 3778) or VKAs (n = 2959). When compared to VKAs, DOACs were associated with similar risks of recurrent venous thromboembolism (weighted HR, 0.80; 95% CI, 0.43-1.46; I² = 0.00), major bleeding (weighted HR, 0.96; 95% CI, 0.57-1.63; I² = 0.59), and all-cause mortality (weighted HR, 1.04; 95% CI, 0.81-1.34; I² = 0.00).

Conclusions: Among octogenarians with venous thromboembolism, DOACs showed a comparable effectiveness and safety compared to VKAs. Our results support the use of DOACs in this high-risk group.