The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis

Abstract

Background Although randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice. Aims To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice. Methods Patients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea’s nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin. Results Of the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54–0.71; 0.60, 0.53–0.69; and 0.71, 0.56–0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51–0.66 and 0.75, 0.60–0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69–1.04), showed a significantly lower MB risk than warfarin. Conclusions Among Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin.

Impact of Reduced-Dose Nonvitamin K Antagonist Oral Anticoagulants on Outcomes Compared to Warfarin in Korean Patients with Atrial Fibrillation: A Nationwide Population-Based Study

“…In another study evaluating the effectiveness and safety of NOACs versus warfarin among the Korean population with AF, NOACs had an overall favorable clinical benefit compared to that of warfarin, although 50-75% of the cohort included patients on reduced-dose NOAC treatment [17]. Similar results were obtained from our previous study in which the risk of S/SE and MB were compared between NOACs (including all dosages) and warfarin in the OAC taking AF patients [35]. Considering that reduced dosing is recommended for patient groups associated with a higher risk of not only bleeding (HAS-BLED) but also for stroke (CHA 2 DS 2 -VASc), this study's results provide additional information on the benefit of NOACs over warfarin in Asian patients requiring anticoagulation for stroke prevention.…”

Real-World Data of Anticoagulant Treatment in Non-valvular Atrial Fibrillation

“…Several studies and meta-analyses (14,15) have described aspects of the anticoagulation of AF with RWD data, although the results sometimes are misleading due to the lack of uniformity of the studies selected in the meta-analysis. The majority compared the performance of the NOACs with the VKA in terms of risk reduction of stroke or major bleeding events (9.11, 12, 14, 16), with or without applying propensity score matching (9). Our results emphasize the importance of anticoagulation to reduce stroke incidence, cardiovascular, and total mortality.…”

“…Although randomized trials provide evidence on the efficacy of anticoagulant treatments, the results may differ from those observed in daily clinical practice. Using real-world data (RWD), the impact of anticoagulant therapy has been analyzed using different sources (9)(10)(11)(12)(13)(14)(15). Electronic health records (EHRs) collect a large amount of information, including data about prevalence, disease control, risk factors, treatments, modifying conditions, and information for surveillance programs (16,17).…”

The Comparison of Therapeutic Efficacy Between Dabigatran Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation

“… 6 Recently, a retrospective study in Asian patients showed that dabigatran was associated with a significantly lower stroke/systemic embolism risk and lower major bleeding risk than warfarin. 22 Taken together, our results suggested that an over inhibition of TG may not be necessary for the prevention of thromboembolism, but it would increase the incidence of hemorrhagic events. It is useful to understand the meaning of TG in clinical practice.…”