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Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study.
Stroke. 2020 Jul; 51(7):2066-2075.S

Abstract

BACKGROUND AND PURPOSE

The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation.

METHODS

This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated.

RESULTS

Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran.

CONCLUSIONS

Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

Authors+Show Affiliations

PELyon (Pharmaco Epidemiology Lyon), Lyon, France (E.V.G., F.J., M.N., F.D., M.B.). Department of Respiratory Medicine, Croix Rousse University Hospital, Lyon, France (E.V.G.). HESPER (Health Services and Performance Research) 7425, University Claude Bernard Lyon 1, Lyon, France (E.V.G.).Hôpital Européen Georges Pompidou, Department of Cardiology, Paris, France (N.D.).Hôpital Louis Mourier, AP-HP, Department of Internal Medicine, Colombes, France (I.M.). Université de Paris, Department of Innovative Therapies in Haemostasis, INSERM, Paris, France (I.M.).Université Paris Descartes, Sorbonne Paris Cité, Equipe d'accueil, 4468, Paris, France (O.H.). Hôpital Broca, Department of Geriatrics, AP-HP, Paris, France (O.H.).PELyon (Pharmaco Epidemiology Lyon), Lyon, France (E.V.G., F.J., M.N., F.D., M.B.).PELyon (Pharmaco Epidemiology Lyon), Lyon, France (E.V.G., F.J., M.N., F.D., M.B.).PELyon (Pharmaco Epidemiology Lyon), Lyon, France (E.V.G., F.J., M.N., F.D., M.B.).Bristol-Myers Squibb, Rueil-Malmaison, France (C.L., F.-E.C., S.G.).Bristol-Myers Squibb, Rueil-Malmaison, France (C.L., F.-E.C., S.G.).Bristol-Myers Squibb, Rueil-Malmaison, France (C.L., F.-E.C., S.G.).INSERM U669, Paris, France (B.F.).PELyon (Pharmaco Epidemiology Lyon), Lyon, France (E.V.G., F.J., M.N., F.D., M.B.).Department of Cardiology, Hôpital Bichat, AP-HP, Paris, France (P.G.S.). Université de Paris, Paris, France (P.G.S.). INSERM U-1148, Paris, France (P.G.S.).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32539675

Citation

Van Ganse, Eric, et al. "Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: the NAXOS Study." Stroke, vol. 51, no. 7, 2020, pp. 2066-2075.
Van Ganse E, Danchin N, Mahé I, et al. Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study. Stroke. 2020;51(7):2066-2075.
Van Ganse, E., Danchin, N., Mahé, I., Hanon, O., Jacoud, F., Nolin, M., Dalon, F., Lefevre, C., Cotté, F. E., Gollety, S., Falissard, B., Belhassen, M., & Steg, P. G. (2020). Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study. Stroke, 51(7), 2066-2075. https://doi.org/10.1161/STROKEAHA.120.028825
Van Ganse E, et al. Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: the NAXOS Study. Stroke. 2020;51(7):2066-2075. PubMed PMID: 32539675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study. AU - Van Ganse,Eric, AU - Danchin,Nicolas, AU - Mahé,Isabelle, AU - Hanon,Olivier, AU - Jacoud,Flore, AU - Nolin,Maëva, AU - Dalon,Faustine, AU - Lefevre,Cinira, AU - Cotté,François-Emery, AU - Gollety,Sabrina, AU - Falissard,Bruno, AU - Belhassen,Manon, AU - Steg,Ph Gabriel, Y1 - 2020/06/16/ PY - 2020/6/17/pubmed PY - 2020/6/17/medline PY - 2020/6/17/entrez KW - anticoagulant KW - atrial fibrillation KW - mortality KW - rivaroxaban KW - safety SP - 2066 EP - 2075 JF - Stroke JO - Stroke VL - 51 IS - 7 N2 - BACKGROUND AND PURPOSE: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. METHODS: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. RESULTS: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. CONCLUSIONS: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials. SN - 1524-4628 UR - https://www.unboundmedicine.com/medline/citation/32539675/Comparative_Safety_and_Effectiveness_of_Oral_Anticoagulants_in_Nonvalvular_Atrial_Fibrillation:_The_NAXOS_Study L2 - https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.028825?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -