Discontinuation risk comparison among ‘real-world’ newly anticoagulated atrial fibrillation patients: Apixaban, warfarin, dabigatran, or rivaroxaban

<div><p>Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan^® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80–0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68–0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55–0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38–1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17–1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment.</p></div

Baseline patient characteristics and treatment follow-up period.

<p>Baseline patient characteristics and treatment follow-up period.</p

Cumulative incidence of discontinuation among newly anticoagulated non-valvular atrial fibrillation patients.

<p>(Upper panel) Cumulative incidence of discontinuation during the follow-up period. The unadjusted cumulative incidence of discontinuation was lower among patients initiated on apixaban compared to patients inititated on other oral anticoagulants. (Lower panel) The number of patients at risk for discontinuation at varying points during the follow-up.</p

Adjusted hazard ratios of discontinuation.

<p>Adjusted hazard ratios of discontinuation.</p

Patient selection criteria.

<p>Study population flow chart with inclusion and exclusion criteria used to select 45,361 patients. NOAC: non-vitamin K antagonist oral anticoagulant; VTE: venous thromboembolism.</p

Study period depiction.

<p>Study period for patients initiating apixaban, dabigatran, rivaroxaban, and warfarin. AF: atrial fibrillation.</p

Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach

<div><p>Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60–0.81) and major bleeding (HR: 0.59, 95% CI: 0.53–0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49–0.81) and major bleeding (HR: 0.59, 95% CI: 0.49–0.71). In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice.</p><p><b>Trial registration:</b> Clinicaltrials.Gov Identifier: <a href="https://clinicaltrials.gov/ct2/show/NCT03087487" target="_blank">NCT03087487</a>.</p></div

Baseline characteristics for PSM-adjusted 5 mg BID apixaban and warfarin and 2.5 mg BID apixaban and warfarin patients.

<p>Baseline characteristics for PSM-adjusted 5 mg BID apixaban and warfarin and 2.5 mg BID apixaban and warfarin patients.</p

Number of events and incidence rates of clinical outcomes within 1 year for 2.5 mg BID apixaban and warfarin patients.

<p>Number of events and incidence rates of clinical outcomes within 1 year for 2.5 mg BID apixaban and warfarin patients.</p

Cumulative incidence and hazard ratios of major bleeding among 5 mg BID apixaban and warfarin patients.

<p><b>(A)</b> Cumulative incidence of major bleeding among propensity-score–matched 5 mg BID apixaban and warfarin patients. <b>(B)</b> Hazard ratio of major bleeding for propensity-score–matched 5 mg BID apixaban and warfarin patients. BID, twice daily.</p