Effectiveness and safety of oral anticoagulants in non-valvular atrial fibrillation patients with prior bleeding events: a retrospective analysis of administrative claims databases.

INTRODUCTION: There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding. METHODS: This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB. RESULTS: A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated with apixaban, 12,500 (5.1%) with dabigatran, 38,246 (15.6%) with rivaroxaban, and 138,723 (56.7%) with warfarin. Apixaban (hazard ratio [HR]: 0.76 [95% CI: 0.70, 0.83]) and rivaroxaban (HR: 0.79 [95% CI: 0.71, 0.87]) had a lower risk of stroke/SE vs. warfarin. Apixaban (HR: 0.67 [95% CI: 0.64, 0.70]) and dabigatran (HR: 0.88 [95% CI: 0.81, 0.96]) had a lower risk of MB vs. warfarin. Apixaban patients had a lower risk of stroke/SE vs. dabigatran (HR: 0.70 [95% CI: 0.57, 0.86]) and rivaroxaban (HR: 0.85 [95% CI: 0.76, 0.96]) and a lower risk of MB than dabigatran (HR: 0.73 [95% CI: 0.67, 0.81]) and rivaroxaban (HR: 0.64 [95% CI: 0.61, 0.68]). CONCLUSIONS: In this real-world analysis of a large sample of NVAF patients with prior bleeding, NOACs were associated with similar or lower risk of stroke/SE and MB vs. warfarin and variable risk of stroke/SE and MB against each other.

Delaying clinical events among patients with non-valvular atrial fibrillation treated with oral anticoagulants: Insights from the ARISTOPHANES study.

BACKGROUND: Oral anticoagulants (OACs) mitigate stroke and systemic embolism (SE) risk in non-valvular atrial fibrillation (AF) patients but can increase the risk of major bleeding (MB). This study analyzed the gains in event-free time for these outcomes among OAC treatment options represented in the ARISTOPHANES study. METHODS: This sub-analysis consisted of NVAF patients who initiated warfarin, apixaban, dabigatran, or rivaroxaban from 01JAN2013-30SEP2015, with data pooled from Medicare and 4 US commercial claims databases. Propensity score matching was conducted between non-vitamin K antagonist OAC (NOAC) and warfarin cohorts in each database and results were pooled. Laplace regression was used to evaluate the delay in time to stroke/SE and MB events between NOACs and warfarin and between NOACs after the first 12-months of follow-up. RESULTS: The population included 466,991 patients (167,413 warfarin; 108,852 apixaban; 37,724 dabigatran; and 153,002 rivaroxaban). Event-free time gain (95% confidence interval) for apixaban versus warfarin was 101 days (78- 124) for stroke/SE and 116 (103- 130) days for MB. The gain in event-free time for dabigatran versus warfarin was 45 days (3- 87) for stroke/SE and 92 (68- 116) days for MB. The gain in event-free time for rivaroxaban versus warfarin was 63 days (42- 84) for stroke/SE but event-free time decreased by 18 (-31-6) days for MB. CONCLUSIONS: Over 12 months after initiation, apixaban and dabigatran conferred progressive increases in event free time for stroke/SE and MB vs warfarin, whereas rivaroxaban conferred an increase in stroke/SE-free time but a loss in MB-free time vs warfarin.

Impact of apixaban treatment discontinuation on the risk of hospitalization among patients with nonvalvular atrial fibrillation and COVID-19.

INTRODUCTION: This study evaluated the risk of hospitalization among nonvalvular atrial fibrillation (NVAF) patients with an outpatient COVID-19 diagnosis who discontinued vs continued apixaban treatment. METHODS: Adult patients with NVAF with an apixaban prescription prior to an outpatient COVID-19 diagnosis were identified from Optum Clinformatics claims database (1 April 2020-31 March 2021). Continuers were those who continued apixaban as of the index date (date of initial outpatient COVID-19 diagnosis) and discontinuers were those who had the last day of apixaban supply on or before index. Patients were followed from COVID-19 diagnosis to change of continuation/discontinuation status, switch, death, end of continuous coverage or study end, whichever occurred first. Inverse probability treatment weighting (IPTW) was performed to balance cohorts. Cox proportional hazard models were used to compare the risk of all-cause hospitalization and hospitalization for ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), bleeding and mortality. RESULTS: A total of 7869 apixaban patients with COVID-19 were included: 6676 continuers (84.8%) and 1193 discontinuers (15.2%). Compared with continuers, discontinuers had a higher risk of all-cause hospitalization (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.08-1.40), IS (HR: 2.00; 95% CI: 1.03-3.87), VTE (HR: 2.37; 95% CI: 1.06-5.27) and mortality (HR: 2.28; 95% CI: 1.85-2.80). There were no significant differences in the risk of MI (HR: 1.01; 95% CI: 0.54-1.90) or bleeding-related hospitalization (HR: 1.13; 95% CI: 0.73-1.76). CONCLUSION: NVAF patients with COVID-19 who discontinued apixaban had a higher risk of hospitalization and thrombotic events vs those who continued apixaban, with no significant difference in bleeding-related hospitalization.

The Real-World Treatment of Hemorrhages Associated With Dabigatran and Rivaroxaban: A Multicenter Evaluation.

PURPOSE: Adoption of the target-specific oral anticoagulants (TSOACs) has been slow; accordingly, lack of guidance for emergent reversal confounded by the need for "direct" reversal agents has contributed significantly to warfarin entrenchment in the medical community. The purpose of this analysis is to provide real-world experiences regarding the management of the hemorrhaging patient secondary to dabigatran and rivaroxaban. METHODS: Retrospective review of patients admitted with a hemorrhage secondary to dabigatran or rivaroxaban were evaluated. Descriptive statistics were utilized for analysis. RESULTS: Four hundred forty-four patients were screened for inclusion into the study; notably, 419 (94%) of the patients were excluded because the bleed was secondary to warfarin therapy. Of those included in this analysis (n = 25), gastrointestinal bleeding accounted for 21 events (84%), followed by intracranial (n = 2; 8%) and epistaxis (n = 2; 8%). Two patients (8%) expired during admission and 6 patients (24%) expired within 6 months after discharge from the hospital. Three (12%) minor bleeds, 7 (28%) major bleeds, and 15 (60%) life-threatening bleeds were identified. Minor bleeds required careful monitoring, supportive care, and cessation of anticoagulation therapy, whereas increasing severity required multiple interventions with prothrombin complex concentrate, recombinant activated factor 7, fresh frozen plasma, packed red blood cells, cryoprecipitate, and platelets. CONCLUSION: The approach to the management of bleeding events borne from TSOACs has proven to be very heterogeneous. In the midst of this observation period, these facilities developed protocols, which created a stratification of bleeds and a more regimented approach to managing them. Although bleeding is less with new agents, the creation of pathways/algorithms for the management of TSOACs and education regarding clinical decision-making may be beneficial for the expeditious and appropriate management when these events arise.