Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

BACKGROUND AND AIMS: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. METHODS: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. RESULTS: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2. CONCLUSIONS: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2.

Discontinuation of direct oral anticoagulants among patients with atrial fibrillation according to gender and cohabitation status: a nationwide cohort study.

AIMS: The aim of this study was to evaluate the risk of discontinuing treatment with direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF) according to cohabitation status and gender. METHODS AND RESULTS: Using the Danish national registers, we identified 32 364 patients with AF aged 40-90 years undergoing treatment with DOACs. The study period was from 2013 to 2017, and patients were followed for 2 years, or until death, outcome, or emigration. The main outcome was discontinuation of DOAC treatment for at least 30 days. The absolute 2-year risk of DOAC discontinuation was highest among men living alone [35.7%, 95% confidence interval (CI): 37.3-34.1%]. Men living alone had a 4.6% (95% CI: 6.4-2.8%) higher absolute risk of discontinuation and a 12% [hazard ratio (HR): 1.12, 95% CI: 1.04-1.20] higher relative risk of discontinuation compared with men living with a partner. Female patients living alone likewise had a higher absolute risk of DOAC discontinuation (2.6%, 95% CI: 4.4-0.09%) compared with female patients living with a partner, yet no statistically significant difference in relative risk. In an analysis evaluating gender, we found male gender to be associated with a significantly higher relative risk of DOAC discontinuation (HR: 1.33, 95% CI: 1.26-1.40) compared with female gender (P-value for interaction with cohabitant status = 0.5996). CONCLUSION: In this nationwide population study, male gender and living alone were associated with a higher risk of DOAC discontinuation among patients with AF.

Osteoporotic Fractures in Patients With Atrial Fibrillation Treated With Conventional Versus Direct Anticoagulants.

BACKGROUND: Elderly patients in long-term treatment with vitamin K antagonists (VKAs) are at high risk of osteoporotic fractures compared with the background population. It has been speculated that the choice of oral anticoagulant (OAC) may affect the risk of osteoporotic fractures. OBJECTIVES: The risk of osteoporotic fractures was evaluated among patients with atrial fibrillation treated with VKA or direct oral anticoagulants (DOACs). METHODS: Patients were identified using the Danish national registries. Patients were included only if they had no prior use of osteoporosis medication and they had undergone 180 days of OAC treatment. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint. RESULTS: Overall, 37,350 patients were included. The standardized absolute 2-year risk of any fracture was low among DOAC-treated patients (3.1%; 95% CI: 2.9% to 3.3%) and among VKA-treated patients (3.8%; 95% CI: 3.4% to 4.2%). DOAC was associated with a significantly lower relative risk of any fracture (hazard ratio [HR]: 0.85; 95% CI: 0.74 to 0.97), major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with DOAC had a significantly lower relative risk of experiencing any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93). CONCLUSIONS: In a nationwide population, the absolute risk of osteoporotic fractures was low among patients with atrial fibrillation on OAC, but DOAC was associated with a significantly lower risk of osteoporotic fractures compared with VKA.