Direct Oral Anticoagulants in Patients with Atrial Fibrillation (DOACs Vs Warfarin)

NCT03596502 | Completed

• 1 other identifier: Q16-13B
• Study Type: observational
• Target: 402,764
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for stroke prevention in patients with non-valvular atrial fibrillation (AF). The comparison of DOACs versus oral vitamin K antagonists, in particular warfarin, is of interest. The investigators will carry out separate population-based, matched cohort studies, using health administrative databases in seven Canadian provinces. New users of oral anticoagulants (DOACs or warfarin) for stroke prevention in non-valvular AF will be eligible to enter the cohorts. Follow-up will continue until a hospitalization or emergency department visit for a stroke. The results from the separate sites will be combined by meta-analysis to provide an overall assessment of the safety and effectiveness of the different anticoagulation regimens in stroke prevention in AF. The investigators hypothesize that DOACs and warfarin will have similar safety and effectiveness profiles.

Conditions

Atrial Fibrillation; Ischemic Stroke; Systemic Embolization; Major Bleed; Myocardial Infarction; All-cause Mortality

Keywords

Direct oral anticoagulants; Safety; Atrial fibrillation; Ischemic stroke; Systemic embolization

Outcome Measures

Primary Outcomes (1)

• Ischemic stroke (IS) or systemic embolization (SE)

  Patients hospitalized or visiting the emergency department (ED) for a stroke or a systemic embolization recorded as the most responsible diagnosis in either the discharge abstract or hospitalization record with the following ICD codes: Ischemic stroke: ICD-9 codes: 434.x; ICD-10 codes: I63.x, I64.x Systemic embolization: ICD-9 codes: 444.x; ICD-10 codes: I74.x

  Patients will be followed from date of first DOAC or warfarin prescription (cohort entry date) until a hospitalization or ED visit for IS or SE, censoring due to death, end of healthcare coverage, or for up to 65 months, whichever occurs first.

Secondary Outcomes (3)

• Major bleeding

  Patients will be followed from date of first DOAC or warfarin prescription (cohort entry date) until a hospitalization or ED visit for major bleed, censoring due to death, end of healthcare coverage, or for up to 65 months, whichever occurs first.

• All-cause mortality

  Patients will be followed from date of first DOAC or warfarin prescription (cohort entry date) until death, end of healthcare coverage, or for up to 65 months, whichever occurs first.

• Myocardial infarction

  Patients will be followed from date of first DOAC or warfarin prescription (cohort entry date) until a hospitalization for a myocardial infarction, censoring due to death, end of healthcare coverage, or for up to 65 months, whichever occurs first.

Study Arms (2)

Direct oral anticoagulants (DOACs)

Patients diagnosed with non-valvular atrial fibrillation who initiated their oral anticoagulation with a DOAC (apixaban, dabigatran or rivaroxaban) at cohort entry date, and did not have a previous prescription for any oral anticoagulant in the prior year.

Drug: Direct oral anticoagulants (DOACs)

Warfarin

Patients diagnosed with non-valvular atrial fibrillation who initiated their oral anticoagulation with warfarin at cohort entry date, and did not have a previous prescription for any oral anticoagulant in the prior year.

Drug: Warfarin

Interventions

Direct oral anticoagulants (DOACs) DRUG

Exposure to DOACs will be defined as a new prescription for apixaban (ATC B01AF02), dabigatran (ATC B01AE07), or rivaroxaban (ATC B01AF01) at cohort entry date in patients diagnosed with non-valvular atrial fibrillation.

Also known as: Eliquis, Pradaxa, Xarelto

Direct oral anticoagulants (DOACs)

Warfarin DRUG

Exposure to warfarin will be defined as a new prescription for warfarin (ATC B01AA03) at cohort entry date in patients diagnosed with non-valvular atrial fibrillation.

Also known as: Coumadin

Warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In each jurisdiction, the investigators will assemble a study cohort that includes all patients newly anticoagulated from the date of the first DOAC approval for stroke prevention in AF (in each site) to the date of the latest data availability at each site, that had a diagnosis of AF within the 3 years prior to the date of the prescription.

You may qualify if:

• Patients with a new prescription for an oral anticoagulant that had a diagnosis of atrial fibrillation or atrial flutter within the 3 years prior to the date of the prescription
• Patients aged 18 years or older (except Alberta, Nova Scotia, and Ontario, where patients will be aged at least 66 years or older)

You may not qualify if:

• Patients with less than one year of data availability prior to cohort entry
• Patients with a diagnosis of valvular disease (including rheumatic heart disease) or prior cardiac valve surgery
• Patients with a diagnosis of venous thromboembolic disease in the year prior to cohort entry
• Patients who underwent hemodialysis in the 90 days prior to cohort entry
• Patients with a hip, femur, or knee surgery in the 30 days prior to cohort entry
• Patients with a diagnosis of antiphospholipid syndrome

Sponsors & Collaborators

• Canadian Network for Observational Drug Effect Studies, CNODES: lead
• Drug Safety and Effectiveness Network, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

Related Publications (1)

• Durand M, Schnitzer ME, Pang M, Carney G, Eltonsy S, Filion KB, Fisher A, Jun M, Kuo IF, Renoux C, Paterson JM, Quail J, Matteau A; Canadian Network for Observational Drug Effect Studies Investigators. Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study. CMAJ Open. 2020 Dec 18;8(4):E877-E886. doi: 10.9778/cmajo.20200055. Print 2020 Oct-Dec.

  PMID: 33355273 BACKGROUND

Related Links

• This is the website describing the general functions of the organization, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Atrial Fibrillation; Ischemic Stroke; Myocardial Infarction

Interventions

N(4)-oleylcytosine arabinoside; apixaban; Dabigatran; Rivaroxaban; Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Myocardial Ischemia; Infarction; Ischemia; Necrosis

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Officials

• Madeleine Durand, MD, MSc, FRCPC

  Centre de Recherche du Centre Hospitalier de l'Université de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: July 24, 2018
• Study Start: February 1, 2018
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 19, 2024

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)