Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients With Active Cancer.

BACKGROUND: Patients with cancer are more likely to develop nonvalvular atrial fibrillation (NVAF). Currently there are no definitive clinical trials or treatment guidelines for NVAF patients with concurrent cancer. OBJECTIVES: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (stroke/SE) and major bleeding (MB) among NVAF patients with active cancer who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS: A retrospective observational study was conducted in NVAF patients with active cancer who newly initiated apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with the use of Medicare and 4 U.S. commercial claims databases. Cox models were used to estimate the risk of stroke/SE and MB in the pooled propensity score-matched cohorts. RESULTS: A total of 40,271 patients were included, with main cancer types of prostate (29%), female breast (17%), genitourinary (14%), and lung (13%). Compared with warfarin, apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.45-0.78) and MB (HR: 0.58; 95% CI: 0.50-0.68); dabigatran and rivaroxaban had similar risks of stroke/SE (dabigatran: HR: 0.88 [95% CI: 0.54-1.41]; rivaroxaban: HR: 0.82 [95% CI: 0.62-1.08]) and MB (dabigatran: HR: 0.76 [95% CI: 0.57-1.01]; rivaroxaban: HR: 0.95 [95% CI: 0.85-1.06]). Risks of stroke/SE and MB varied among NOAC-NOAC comparisons, while consistent treatment effects were seen for all treatment comparisons across key cancer types. CONCLUSIONS: Among this cohort of NVAF patients with active cancer, the risk of stroke/SE and MB varied among oral anticoagulants and were consistent across cancer types.

Oral Anticoagulants for Nonvalvular Atrial Fibrillation in Patients With High Risk of Gastrointestinal Bleeding.

Importance: Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. Objective: To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin. Design, Setting, and Participants: This retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015. Exposures: New prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period). Main Outcomes and Measures: Six propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs). Results: A total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16). Conclusions and Relevance: In this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.

Effectiveness and Safety of Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Diabetes Mellitus.

OBJECTIVE: To address gaps in the data comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among patients with nonvalvular atrial fibrillation (NVAF) and diabetes. PATIENTS AND METHODS: A retrospective study was conducted on patients with NVAF and diabetes newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with Medicare data from the US Centers for Medicare & Medicaid Services and 4 other US commercial claims databases. One-to-one propensity score matching was completed between NOACs and warfarin and between NOACs in each database, and the results were pooled. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB). RESULTS: A total of 154,324 patients were included in the 6 matched cohorts, with a mean follow-up time of 6 to 8 months. Compared with warfarin, apixaban (hazard ratio [HR], 0.67; 95% CI, 0.57-0.77) and rivaroxaban (HR, 0.79; 95% CI, 0.71-0.89) were associated with a lower risk of stroke/SE; dabigatran (HR, 0.84; 95% CI, 0.67-1.07) was associated with a similar risk of stroke/SE. Apixaban (HR, 0.60; 95% CI, 0.56-0.65) and dabigatran (HR, 0.78; 95% CI, 0.69-0.88) were associated with a lower risk of MB; rivaroxaban (HR, 1.02; 95% CI, 0.94-1.10) was associated with a similar risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of MB. Compared with rivaroxaban, dabigatran was associated with a lower risk of MB. CONCLUSION: This study-the largest observational study to date of patients with NVAF and diabetes taking anticoagulants-found that NOACs were associated with variable rates of stroke/SE and MB compared with warfarin. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03087487.