Dataset Information

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study.

ABSTRACT:

Background

Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.

Methods

We conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses.

Results

We included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85).

Interpretation

In this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation.

Trial registration

ClinicalTrials.gov, no. NCT03596502.

SUBMITTER: Durand M

PROVIDER: S-EPMC7759115 | biostudies-literature | 2020 Oct-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study.

Durand Madeleine M Schnitzer Mireille E ME Pang Menglan M Carney Greg G Eltonsy Sherif S Filion Kristian B KB Fisher Anat A Jun Min M Kuo I Fan IF Renoux Christel C Paterson J Michael JM Quail Jacqueline J Matteau Alexis A

CMAJ open 20201001 4

<h4>Background</h4>Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.<h4>Methods</h4>We conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used he ...[more]

PMID: 33355273

Similar Datasets

Project description:BackgroundDirect oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population.MethodsRetrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts.ResultsPatients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29-1.35) and a lower risk for bleeding (0.89; 0.88-0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82-2.03), apixaban (1.52; 1.46-1.58), and rivaroxaban (1.13; 1.10-1.17) but not for edoxaban (0.88; 0.74-1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83-0.88), apixaban (0.71; 0.70-0.73), and edoxaban (0.29; 0.17-0.51) but not for rivaroxaban (1.03; 1.01-1.04).ConclusionsThis study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.

Project description:BackgroundDirect oral anticoagulants (DOACs) and warfarin are usually used for people with atrial fibrillation (AF). However, for the AF patients at risk of falling, the effectiveness and safety outcomes of DOACs compared with warfarin remain unclear. Therefore, we performed a meta-analysis regarding the effectiveness and safety of DOACs vs. warfarin in AF patients at risk of falling.MethodsA search of the PubMed and Embase databases until November 2021 was performed. We included studies if they satisfied the following criteria: (1) study type: randomized clinical trials or observational cohort studies. (2) Comparisons: effectiveness and/or safety of DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) compared with warfarin. (3) Study data: the sample size, the number of events in the VKAs or DOACs groups, adjusted risk ratios (RRs), and 95% confidence intervals (CIs). (4) Study outcomes: stroke or systemic embolism (SSE), ischemic stroke, myocardial infarction (MI), all-cause death, and cardiovascular death; major bleeding, major or clinically relevant non-major (CRNM) bleeding, intracranial bleeding, gastrointestinal bleeding, and any bleeding. (5) Study population: patients at risk of falling. According to the Morse Fall Scale, the risk of falling relates to the history of falling, secondary diagnosis, ambulatory aids, intravenous therapy, type of gait, and mental status. In this meta-analysis, if the patient's MFS score is ≥25 points, he will be thought of as having the risk of falling. The adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method.ResultsThree cohort studies were included in our study. For the effectiveness outcomes, the use of DOACs was only associated with a significantly reduced risk of hemorrhagic stroke (RR = 0.28, 95%CI:0.10-0.75) compared with warfarin, but there were no significant differences in stroke or systemic embolism (SSE) (RR = 0.87, 95%CI:0.70-1.08), cardiovascular death (RR = 0.97, 95%CI:0.73-1.29) and all-cause death (RR = 0.90, 95%CI:0.72-1.11). For the safety outcomes, the use of DOACs was significantly associated with reduced risks of major or clinically relevant non-major bleeding (RR = 0.77, 95%CI:0.61-0.98) and intracranial bleeding (RR = 0.26, 95%CI:0.11-0.66) but not major bleeding (RR = 0.78, 95%CI:0.58-1.06).ConclusionsCompared with warfarin, the use of DOACs in AF patients at risk of falling is significantly associated with reduced risks of hemorrhagic stroke, major or clinically relevant non-major bleeding, and intracranial bleeding.

Dataset Information

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study.

Background

Methods

Results

Interpretation

Trial registration

Publications

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study.

Similar Datasets

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