Direct oral anticoagulants versus vitamin K antagonists in non-valvular atrial fibrillation (Q16-13B)
What is the issue?
- Both vitamin K antagonists (mostly warfarin) and direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban and edoxaban) are used for anticoagulation therapy for stroke prevention in patients with non-valvular atrial fibrillation (NVAF).
- The use of DOACs is increasing due to fewer drug-drug and drug-food interactions and less need for monitoring.
What was the aim of the study?
- This study, evaluated the safety and effectiveness (clinical benefits and harms) of DOACs in patients with NVAF compared to warfarin.
How was the study conducted?
- We conducted a retrospective propensity score-matched, cohort study using administrative healthcare records on 255,851 patients newly prescribed anticoagulants, identified from seven Canadian provinces.
- Patients with NVAF newly prescribed DOACs (dabigatran, rivaroxaban or apixaban) were matched to those newly prescribed warfarin.
- The primary outcome was ischemic stroke or systemic embolization; secondary outcomes included major bleeding, all-cause mortality, myocardial infarction, and a composite outcome of all strokes, major bleeding and all-cause mortality.
- Hazard Ratios (HR) and 95% confidence intervals (CI) were estimated and pooled across sites using meta-analysis.
What did the study find?
- The study cohort included 128,273 new users of DOACs matched to 128,273 new users of warfarin, followed for an average of 2 years.
- Comparing DOACs with warfarin showed:
- A similar risk of ischemic stroke (HR 1.02; 95% CI: 0.87 to 1.20),
- A lower risk of major bleeding (HR 0.81; 95% CI:0.69 to 0.97),
- A lower risk of the composite outcome of all strokes, major bleeding and all-cause mortality (HR 0.81; 95% CI: 0.74 to 0.89) and
- A lower risk of all-cause mortality (HR 0.81; 95% CI:0.78 to 0.8).
- This large pan-Canadian study further demonstrates the ability of CNODES to analyze a large amount of anonymous patient data to contribute to the understanding of a drug’s risks and benefits after they have been marketed.
- The results of this study, the most comprehensive of its kind in Canada, are consistent with previous research.
- DOACs and warfarin provide similar effectiveness for ischemic stroke prevention for patients with NVAF in Canada.
- However, DOACs carry a lower risk of major bleeding and all-cause mortality compared with warfarin.
- This large pan-Canadian study provides key data on the relative benefits and harms of DOACs as compared with warfarin for the treatment of patients with non-valvular atrial fibrillation.
- These data can assist in informing physicians prescribing these medications along with other evidence and patient preferences.
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Durand M, Schnitzer M, Pang M, Carney G, Eltonsy S, Filion KB, Fisher A, Jun M, Matteau A, Paterson JM, Quail J, Renoux C for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis. Br J Clin Pharmacol. 2021 Jun;87(6):2589-2601.
Durand M, Schnitzer M, Pang M, Carney G, Eltonsy S, Filion KB, Fisher A, Jun M, Kuo IF, Renoux C, Paterson JM, Quail J and Matteau A for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Comparative Effectiveness and Safety of Direct Oral Anticoagulants compared to vitamin K antagonists in Non-Valvular Atrial Fibrillation: A Multi-center Observational Cohort Study. CMAJ Open 2020 Dec 18;8(4):E877-E886.