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

Abstract

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.

Trial registration: Clinicaltrials.Gov Identifier: NCT03087487.

Conflict of interest statement

Competing Interests: XL, MH, KG, KF, AN, and XP are employees of Bristol-Myers Squibb Company with ownership of stocks in Bristol-Myers Squibb Company. AK is an employee of STATinMED Research, a paid consultant to Bristol-Myers Squibb Company and Pfizer, Inc. in connection with conducting this study. XL and JM are employees of Pfizer Inc., with ownership of stocks in Pfizer Inc. RH is a former employee of Pfizer Inc., with ownership of stocks in Pfizer Inc. SD is a consultant for Bayer/Janssen, Bristol-Myers Squibb Company/Pfizer Inc., Daiichi-Sankyo, Portola, and Boehringer Ingelheim, and has been on the speakers’ bureau for Janssen, Bristol-Myers Squibb Company/Pfizer Inc., and Boehringer Ingelheim. GYHL has served as a consultant for Bayer/Janssen, Merck, Sanofi, Bristol-Myers Squibb Company/Pfizer Inc., Daiichi-Sankyo, Biotronik, Medtronic, Portola, and Boehringer Ingelheim, and has been on the speakers’ bureau for Bayer, Bristol-Myers Squibb Company/Pfizer Inc., Boehringer Ingelheim, Daiichi-Sankyo, and Medtronic. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Patient selection flowchart.

*15 Patients had both doses of apixaban on the index date, so they were not included in the analysis. AF: atrial fibrillation; BID: twice daily; ICD-10-CM: International Classification of Disease, 10th Revision, Clinical Modification; VTE: venous thromboembolism.

Fig 2. Cumulative incidence and hazard ratios of stroke/systemic embolism among 5 mg BID apixaban/warfarin patients.

(A) Cumulative incidence of stroke/SE among propensity-score–matched 5 mg BID apixaban and warfarin patients. (B) Hazard ratios of stroke/SE for propensity-score–matched 5 mg BID apixaban and warfarin patients. BID, twice daily; stroke/SE, stroke/systemic embolism.

Fig 3. Cumulative incidence and hazard ratios of stroke/systemic embolism among 2.5 mg BID apixaban/warfarin patients.

(A) Cumulative incidence of stroke/SE among propensity-score–matched 2.5 mg BID apixaban and warfarin patients. (B) Hazard ratios of stroke/SE for propensity-score–matched 2.5 mg BID apixaban and warfarin patients. Footnote: BID: twice daily; stroke/SE, stroke/systemic embolism.

Fig 4. Cumulative incidence and hazard ratios of major bleeding among 5 mg BID apixaban and warfarin patients.

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

Fig 5. Cumulative incidence and hazard ratios of major bleeding among 2.5 mg BID apixaban and warfarin patients.

(A) Cumulative incidence of major bleeding among propensity-score–matched 2.5 mg BID apixaban and warfarin patients. (B) Hazard ratio of major bleeding for propensity-score–matched 2.5 mg BID apixaban and warfarin patients. BID: twice daily; GI: gastrointestinal bleeding; ICH: intracranial hemorrhage.