How do the clinical safety and efficacy of new oral anticoagulants compare to warfarin, ASA, clopidogrel, or ASA + clopidogrel in preventing morbidity and mortality in patients with non-valvular atrial fibrillation? Are there any differences in clinical safety and efficacy depending on the dose of ASA?

In patients with non-valvular atrial fibrillation, what is the impact on the clinical safety and efficacy of new oral anticoagulants of the following: CHADS2 score, time spent in the therapeutic range (applicable only to warfarin), age, weight, renal function, history of gastrointestinal bleed, concurrent use of antiplatelet agents (when on oral anticoagulants) or NSAIDs?

What is the cost-effectiveness, from a public payer's perspective, of new oral anticoagulants compared to warfarin, ASA, clopidogrel or ASA + clopidogrel in preventing morbidity and mortality in patients with non-valvular atrial fibrillation?

What is the cost-effectiveness, from a public payer's perspective, of new oral anticoagulants compared to warfarin, ASA, clopidogrel or ASA + clopidogrel in preventing morbidity and mortality in patients with non-valvular atrial fibrillation based on the CHADS2 score?

Published literature was identified by searching the following bibliographic databases: MEDLINE (1946- ) with in-process records and daily updates via Ovid; Embase (1974- ) via Ovid; Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid; and PubMed. Methodological filters were applied to limit retrieval to randomized controlled trials and controlled clinical trials. Retrieval was limited to English language articles and studies published after 1988. Conference abstracts were excluded from the search results. The initial search was completed on June 7, 2012. Regular alerts have been established.

Inclusion criteria:

Published RCTs

Exclusion criteria:

Studies in languages other than English

Non-randomized studies

Atrial fibrillation is the most common cardiac arrhythmia, and is associated with high morbidity and mortality, much of which is due to thromboembolism, especially ischemic stroke. Therefore, preventing these events with antithrombotic strategies is an important part of managing atrial fibrillation patients.

Inclusion criteria: individuals with non-valvular AF requiring anticoagulation (including all risk levels and regardless of any comorbidities).

Inclusion criteria:

Apixaban 2.5 mg or 5 mg BID

Dabigatran 110 mg or 150 mg BID

Rivaroxaban 20 mg OD

ASA

Clopidogrel 75 mg OD

Dose-adjusted Vitamin K Antagonist (warfarin and acenocoumarol)

Placebo

Please refer to "intervention(s)" above.

Primary outcomes

All-cause stroke or systemic embolism

Major bleeding (ISTH definition)

All-cause mortality

Secondary outcomes

Intracranial bleeding (including intracerebral haemorrhage)

Cardiovascular mortality

Ischemic/uncertain stroke or systemic embolism (including myocardial infarction)

Life-threatening bleeds

Extracranial hemorrhage

Minor bleeds

Pulmonary embolism

Transient ischemic attacks

Non-cardiovascular mortality

Studies were included if they met the inclusion criteria listed in the pre-specified review protocol. Article selection was performed by two independent review authors in a standardized manner. Any uncertainties were resolved by discussion and consensus.

Findings will be interpreted in light of the heterogeneity of the individual studies (differences in design, study populations, interventions or exposures, and outcome measures) and the validity assessment of the included trials.

The clinical and economic assessments will be performed by indirect/mixed treatment comparisons, with the use of a network meta-analysis.

CHADS2 score

Time in Therapeutic Range

Age

Weight

Renal function

History of GI bleed

Concurrent use of antiplatelet agents (when on oral anticoagulants) or NSAID

Prior Vitamin K Antagonist use

Type of atrial fibrillation

Essential messages from the review will be communicated through knowledge mobilization activities.

Trevor Richter

Canadian Agency for Drugs and Technologies in Health (CADTH)

600-865 Carling Avenue

Ottawa, Ontario K1S 5S8

trevorr@cadth.ca

Canadian Agency for Drugs and Technologies in Health (CADTH)

www.cadth.ca

Mrs Kasandra Gauthier, CADTH
Dr Annie Bai, CADTH
Mrs Kristen Moulton, CADTH
Mrs Carolyn Spry, CADTH
Dr George Wells, University of Ottawa Heart Institute, Ottawa, Ontario
Dr Doug Coyle, University of Ottawa, Ottawa, Ontario
Mr Chris Cameron, University of Ottawa Heart Institute, Ottawa, Ontario
Dr Trevor Richter, CADTH

Wells et al. Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation. CADTH, 2012. Online: www.cadth.ca/media/pdf/NOAC_Therapeutic_Review_final_report.pdf

10 May 2012

01 April 2013

Canadian Agency for Drugs and Technologies in Health (CADTH)

None known

English

Canada

Subject indexing assigned by CRD

Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Thrombosis;

The review protocol will soon be published on the CADTH website.

27 July 2012

27 July 2012