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Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study

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Abstract
Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs.Methods: AF patients initiating anticoagulation between 2013-2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose.Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64-0.72)), all-cause mortality (HR 0.76, 95%CI (0.74-0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91-0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66-0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83-0.90); HR 0.86, 95%CI (0.83-0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83-0.99); HR 0.86, 95%CI (0.81-0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80-0.92)) and edoxaban (HR 0.79, 95%CI (0.72-0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively.Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran.
Keywords
ANTAGONIST ORAL ANTICOAGULANTS, STROKE PREVENTION, REAL-WORLD, WARFARIN, METAANALYSIS, EFFICACY, DISEASE, RISK, atrial fibrillation, NOAC, VKA, anticoagulant, thromboembolism, bleeding, mortality, myocardial infarction

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MLA
Grymonprez, Maxim, et al. “Long-Term Comparative Effectiveness and Safety of Dabigatran, Rivaroxaban, Apixaban and Edoxaban in Patients with Atrial Fibrillation: A Nationwide Cohort Study.” FRONTIERS IN PHARMACOLOGY, vol. 14, FRONTIERS MEDIA SA, 2023, doi:10.3389/fphar.2023.1125576.
APA
Grymonprez, M., De Backer, T., Bertels, X., Steurbaut, S., & Lahousse, L. (2023). Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study. FRONTIERS IN PHARMACOLOGY, 14. https://doi.org/10.3389/fphar.2023.1125576
Chicago author-date
Grymonprez, Maxim, Tine De Backer, Xander Bertels, Stephane Steurbaut, and Lies Lahousse. 2023. “Long-Term Comparative Effectiveness and Safety of Dabigatran, Rivaroxaban, Apixaban and Edoxaban in Patients with Atrial Fibrillation: A Nationwide Cohort Study.” FRONTIERS IN PHARMACOLOGY 14. https://doi.org/10.3389/fphar.2023.1125576.
Chicago author-date (all authors)
Grymonprez, Maxim, Tine De Backer, Xander Bertels, Stephane Steurbaut, and Lies Lahousse. 2023. “Long-Term Comparative Effectiveness and Safety of Dabigatran, Rivaroxaban, Apixaban and Edoxaban in Patients with Atrial Fibrillation: A Nationwide Cohort Study.” FRONTIERS IN PHARMACOLOGY 14. doi:10.3389/fphar.2023.1125576.
Vancouver
1.
Grymonprez M, De Backer T, Bertels X, Steurbaut S, Lahousse L. Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study. FRONTIERS IN PHARMACOLOGY. 2023;14.
IEEE
[1]
M. Grymonprez, T. De Backer, X. Bertels, S. Steurbaut, and L. Lahousse, “Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study,” FRONTIERS IN PHARMACOLOGY, vol. 14, 2023.
@article{01HAMEQ26TAXAVBNZXA1FDN4JD,
  abstract     = {{Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs.Methods: AF patients initiating anticoagulation between 2013-2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose.Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64-0.72)), all-cause mortality (HR 0.76, 95%CI (0.74-0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91-0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66-0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83-0.90); HR 0.86, 95%CI (0.83-0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83-0.99); HR 0.86, 95%CI (0.81-0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80-0.92)) and edoxaban (HR 0.79, 95%CI (0.72-0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively.Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran.}},
  articleno    = {{1125576}},
  author       = {{Grymonprez, Maxim and De Backer, Tine and Bertels, Xander and Steurbaut, Stephane and Lahousse, Lies}},
  issn         = {{1663-9812}},
  journal      = {{FRONTIERS IN PHARMACOLOGY}},
  keywords     = {{ANTAGONIST ORAL ANTICOAGULANTS,STROKE PREVENTION,REAL-WORLD,WARFARIN,METAANALYSIS,EFFICACY,DISEASE,RISK,atrial fibrillation,NOAC,VKA,anticoagulant,thromboembolism,bleeding,mortality,myocardial infarction}},
  language     = {{eng}},
  pages        = {{12}},
  publisher    = {{FRONTIERS MEDIA SA}},
  title        = {{Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study}},
  url          = {{http://dx.doi.org/10.3389/fphar.2023.1125576}},
  volume       = {{14}},
  year         = {{2023}},
}

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