Comparative Effectiveness and Safety of New Anticoagulants versus Warfarin

Project number: 
14-065
Approval date: 
Wednesday, August 6, 2014
Principal Investigator: 
Holbrook,Anne
Institution: 
McMaster University
Funding Agency: 
Canadian Institutes of Health Research(CIHR)
Datasets requested: 
Consolidation registry (Ministry of Health)
Hospital Separations (BC Ministry of Health)
consolidation - census geocodes
Medical Services Plan (BC Ministry of Health)
PharmaNet
Consolidation - demographic (Ministry of Health)
Deaths (BC Vital Statistics Agency)
Research objective: 

Research Question:

In a propensity score-matched cohort of anticoagulation-nave patients drawn from the entire adult population of British Columbia, who are receiving a new prescription for a new oral anticoagulant drug (NOAC) or warfarin for atrial fibrillation, what is the comparative time to important clinical event stroke or systemic embolism, or to major bleeding over a median follow-up period of 18 months?

Research Objectives:

a) to clarify the overall comparative effectiveness and safety of dabigatran, apixaban and rivaroxaban versus warfarin in actual clinical practice.
b) to compare and contrast the results with the relevant Phase III randomized trial, RE-LY
c) to identify the key predictors of superior effectiveness and safety (which drug is better for which patients) in vulnerable populations - predictors which are very likely include age, INR control quality in the warfarin patients, remote location (probable lack of ready access to INR testing), and presence of renal impairment.

Hypotheses:

Our primary hypothesis is that the new oral anticoagulants (dabigatran, rivaroxaban, and apixaban) and warfarin, as used in actual practice for atrial fibrillation have similar comparative effectiveness and safety.

Our secondary hypothesis is that key risk factors which define vulnerable groups of patients- notably age, quality of INR control on warfarin, renal function, hepatic function, and anticoagulant adherence, will have an important effect on the comparative incidence of outcomes. It is essential for appropriate tailoring of therapies that we understand which types of patients benefit more from one drug or the other.

The co-primary outcomes in this study are stroke and systemic embolism (benefit) and major bleeding requiring hospitalization (harm). The secondary outcomes are a) net clinical benefit, defined as the composite of key benefit and harm variables- stroke, bleeds requiring hospitalization, myocardial infarction, systemic arterial embolism, pulmonary embolism and death, b) drug discontinuation and c) individual composite item occurrence.


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