Excerpt

Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with substantial morbidity. AF-related mortality is mainly attributable to complications of stroke. Stroke risk can be quantified using a validated tool such as the CHADS₂ score. Warfarin, a vitamin K antagonist, is the standard of care for patients with AF and has demonstrated efficacy in the prevention of stroke. Warfarin has a narrow therapeutic window, produces varied responses among patients, and interacts with some types of food and other drugs, all of which necessitates routine laboratory monitoring.

Improved understanding of the blood clotting cascade has led to the development of several new oral anticoagulants (NOACs) that offer a more targeted mechanism of anticoagulation. These NOACs include the direct thrombin inhibitor, dabigatran, and the direct factor Xa inhibitors, rivaroxaban and apixaban, which have either been approved (dabigatran and rivaroxaban) for use or are currently under regulatory review (apixaban) for the prevention of stroke and systemic embolism (SE) in patients with AF.

Although NOACs have demonstrated efficacy within clinical trials in preventing stroke and SE in patients with AF, the relative effectiveness and cost-effectiveness in clinical practice of these agents is not clear. In addition, the relative effectiveness and cost-effectiveness of the NOACs and warfarin within specific subpopulations of AF patients is not clear.

Evidence-informed recommendations were developed by the Canadian Drug Expert Committee (CDEC) to address the following policy questions:

1. Are there sub-populations of AF patients that would benefit more from using NOACs compared to warfarin?
2. Are there sub-populations of AF patients that would benefit more from one of the NOACs versus another?

At the time of this report, apixaban was not approved by Health Canada for the prevention of stroke and SE in patients with non-valvular AF. Therefore, while the science reports included apixaban in addition to rivaroxaban and dabigatran, the recommendations presented in this report apply at present only to the two NOACs that are approved for this indication in Canada, namely dabigatran and rivaroxaban.

Contents

• ABBREVIATIONS
• BACKGROUND
• SUMMARY OF RECOMMENDATIONS
• RECOMMENDATIONS
  • Reasons for Recommendation 1
  • Reasons for Recommendation 2
• SUMMARY OF THE EVIDENCE
  • Clinical Evidence
  • Economic Evidence
  • Limitations of the Evidence
• DISCUSSION POINTS
  • Efficacy and Cost-Effectiveness
  • Safety
  • Patient Considerations
  • Other Discussion Points
• RESEARCH GAPS
  • Safety
  • Efficacy
• REFERENCES

The Therapeutic Review Recommendations or Advice are formulated following a comprehensive evidence-based review of the medication’s efficacy or effectiveness and safety and an assessment of its cost-effectiveness. Therapeutic Review clinical and economic reports are based on published information available up to the time that CDEC made its recommendation. Input from stakeholders, such as drug manufacturers, patient groups, and health-related professional associations or organizations, is considered in the preparation of this recommendation document.

CDEC is a committee of the Canadian Agency for Drugs and Technologies in Health (CADTH). It makes recommendations and provides advice to Canadian jurisdictions to use in making informed decisions. It is made up of experts in drug evaluation and drug therapy, and public members.

The Final CDEC Therapeutic Review Recommendations or Advice neither takes the place of a medical professional providing care to a particular patient nor is it intended to replace professional advice.

CADTH is not legally responsible for any damages arising from the use or misuse of any information contained in or implied by the contents of this document.

The statements, conclusions, and views expressed herein do not necessarily represent the view of Health Canada or any provincial, territorial, or federal government, or the manufacturer.

Production of this report is made possible through a financial contribution from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Ontario, Prince Edward Island, Saskatchewan, and Yukon.

The Therapeutic Review Framework describes the Therapeutic Review process in detail.¹⁸

Committee Members:

Dr. Robert Peterson (Chair), Dr. Lindsay Nicolle (Vice-Chair), Dr. Ahmed Bayoumi, Dr. Bruce Carleton, Ms. Cate Dobhran, Mr. Frank Gavin, Dr. John Hawboldt, Dr. Peter Jamieson, Dr. Julia Lowe, Dr. Kerry Mansell, Dr. Irvin Mayers, Dr. James Silvius and Dr. Adil Virani

Regrets: Three CDEC members were not available to participate in deliberations and voting.

Conflicts of Interest: None.

Three external Clinical Experts attended the meeting and participated in the discussion, but did not vote on the recommendations.