Comparative safety and effectiveness of oral anticoagulants in key subgroups of patients with non-valvular atrial fibrillation and at high risk of gastrointestinal bleeding: A cohort study based on the French National Health Data System (SNDS).

Risk factors and comorbidities can complicate management of non-valvular atrial fibrillation. We describe and compare real-world safety and effectiveness of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) and vitamin K antagonists (VKAs) in subgroups of patients with non-valvular atrial fibrillation at high risk for gastrointestinal (GI) bleeding, utilizing data from a national quasi-exhaustive French database. Anticoagulant-naïve adults with non-valvular atrial fibrillation with ≥1 gastrointestinal bleeding risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. The following subgroups were evaluated: patients age ≥75 years, receiving concomitant medications, HAS-BLED score ≥3, and chronic kidney disease stage 3-4. Outcomes included major bleeding and stroke/systemic embolism. Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified; characteristics were similar for propensity score-matched subgroups in VKA/DOAC and DOAC/DOAC comparisons. DOACs showed lower risk of major bleeding versus VKAs in all subgroups evaluated (p<0.0001 for all). Apixaban showed lower risk of major bleeding and gastrointestinal bleeding versus rivaroxaban in all subgroups (p≤0.05 for all) and versus dabigatran in elderly patients, patients with HAS-BLED score ≥3, and those receiving concomitant medications (p<0.05 for all). Stroke/systemic embolism risk was lower with apixaban versus rivaroxaban in elderly patients, those with HAS-BLED ≥3, and those receiving concomitant medications; risks were similar for other comparisons. DOACs were associated with improved safety and effectiveness when compared to VKAs among subgroups of non-valvular atrial fibrillation patients at high risk of gastrointestinal bleeding. Apixaban was associated with lower risks of major bleeding, gastrointestinal bleeding, and stroke/systemic embolism versus rivaroxaban as well as lower risk of major bleeding, gastrointestinal bleeding bleed and similar risk of stroke/systemic embolism versus dabigatran among several of these patient subgroups.

Lip GYH ，Benamouzig R ，Martin AC ，Pesce G ，Gusto G ，Quignot N ，Khachatryan A ，Dai F ，Sedjelmaci F ，Chaves J ，Subash R ，Mokgokong R ... -  《PLoS One》

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study.

This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB). Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE). Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified with 162,150 (51.5%) in the apixaban cohort, 88,427 (28.1%) in the rivaroxaban cohort, 16,465 (5.2%) in the dabigatran cohort, and 47,142 (15.0%) in the VKA cohort (mean age 79.0 years, standard deviation 10.5; 51.0% female). A total of 45,124 apixaban-VKAs, 38,737 rivaroxaban-VKAs, 16,415 dabigatran-VKAs, 88,414 apixaban-rivaroxaban, 16,464 apixaban-dabigatran, and 16,459 rivaroxaban-dabigatran pairs were retained after propensity score matching. Apixaban had lower risk of MB versus dabigatran (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83) and rivaroxaban (HR, 0.63; 95% CI, 0.59-0.66). Apixaban had lower risk of GIB versus dabigatran (HR, 0.46; 95% CI, 0.37-0.56) and rivaroxaban (HR, 0.54; 95% CI, 0.49-0.59). Risk of GIB was similar with dabigatran versus rivaroxaban (HR, 1.05; 95% CI, 0.89-1.24). Apixaban had lower risk of stroke/SE versus rivaroxaban (HR, 0.90; 95% CI, 0.84-0.96), while risk was similar versus dabigatran (HR, 1.1; 95% CI, 0.9-1.3). All DOACs had lower risk of MB and stroke/SE versus VKAs (p<0.001 for all). DOACs had improved safety and effectiveness from bleeding and stroke/SE, respectively, versus VKAs among patients with NVAF at high risk for GIB. Apixaban was associated with lower MB and GIB risk versus other DOACs. For stroke/SE, apixaban was associated with reduced risk versus rivaroxaban and similar risk versus dabigatran.

Lip GYH ，Benamouzig R ，Martin AC ，Pesce G ，Gusto G ，Quignot N ，Khachatryan A ，Dai F ，Sedjelmaci F ，Chaves J ，Subash R ，Mokgokong R ... -  《PLoS One》

Effectiveness and safety of direct oral anticoagulants compared to warfarin in treatment naïve non-valvular atrial fibrillation patients in the US Department of defense population.

Gupta K ，Trocio J ，Keshishian A ，Zhang Q ，Dina O ，Mardekian J ，Nadkarni A ，Shank TC ... -  《BMC Cardiovascular Disorders》

Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims.

There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.

Lip GYH ，Noxon V ，Kang A ，Luo X ，Atreja N ，Han S ，Cheng D ，Jiang J ，Abramovitz L ，Deitelzweig S ... -  《-》

Direct Oral Anticoagulants Compared With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease Without Mechanical Valves.

Dawwas GK ，Lewis JD ，Cuker A 《Journal of the American Heart Association》