Authors: Tahir Razzaq, Sweta M. Patel, Irene Robb, Naomi Yates
Background:Direct oral anticoagulants such as rivaroxaban and apixaban are recommended first-line options for the initial treatment of venous thromboembolism (VTE). In patients with unprovoked or recurrent VTEs, extended treatment beyond the initial 3-6 months is recommended. The API-CAT and RENOVE trials evaluated whether dose reduction is appropriate or beneficial in certain patient populations in the extended phase treatment. Both trials concluded that dose reduction had similar VTE recurrence rates with lower bleeding risk compared to full dose treatment. The purpose of this study was to determine if reduced doses of rivaroxaban (10 mg daily) or apixaban (2.5 mg twice daily) offer a safe and effective alternative to the full dose (rivaroxaban 20 mg daily or apixaban 5 mg twice daily) treatment.
Methods: This is a retrospective, IRB-exempt cohort study that included adult patients of Kaiser Permanente Georgia treated with rivaroxaban or apixaban for VTE after completion of the initial 6-month duration. The study population
consisted of patients treated with full dose treatment between January 1, 2023 to June 30, 2024, with clinical outcomes assessed through June 30, 2025. Patients with mechanical heart valves, atrial fibrillation/flutter, and/or concurrent antiplatelet therapy were excluded. The primary outcome of this study was to evaluate the incidence of VTE recurrence and major bleeding events in patients who took reduced or full doses of rivaroxaban or apixaban after the initial VTE treatment period. The secondary outcome was to analyze patient characteristics among those who received either reduced or full doses of rivaroxaban or apixaban to identify factors associated with dose selection. Descriptive statistics were used to assess differences in clinical outcomes and patient characteristics. Chi-squared tests were used to determine statistical significance with a P-value of < 0.05.
Results: A total of 165 patients received either reduced or full dose rivaroxaban or apixaban after the initial VTE treatment period. Of these, 152 patients were included in this analysis. Among this cohort, 14 (9%) patients received dose reduction, including 1 who was on rivaroxaban and 13 on apixaban. A total of 5 patients (3%) experienced a recurrent VTE (2 with rivaroxaban 20 mg daily and 3 with apixaban 5 mg twice daily). Overall, 18 patients (11.8%) experienced either a major or minor bleeding event (10 with rivaroxaban 20 mg daily and 8 with apixaban 5 mg twice daily). Patients who experienced a bleeding event were younger compared to those without bleeding events (mean age 53y vs. 60y; p=0.049). Of the patients who were not dose reduced (n=138), 50 of them (36%) could have benefited from dose reduction. Patients who qualified for dose reduction were significantly older than those who did not (mean age 62y vs 56y; p=0.022)
. Additionally, the Internal Medicine and Oncology departments were among the prescribing departments that had the highest rates of prescribing both full-dose and reduced-dose regimens.
Conclusion: Dose reduction of rivaroxaban and apixaban after the first 6 months of initial VTE treatment demonstrated a lower risk of bleeding. However, full doses of both DOACs were associated with a trend toward higher rates of bleeding and VTE risk. While dose reduction may offer a safer side effect profile, further research may help identify which patient populations would benefit most from dose reduction and its impact on long-term VTE recurrence and bleeding events among those requiring extended VTE treatment. Additionally, pharmacy-led education sessions could help to ensure that dose reductions are performed safely and effectively in clinical practice.
