Non-vitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation: safety issues in the elderly

ABSTRACT

Introduction

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with atrial fibrillation (AF). Since NOACs are predominantly used in the elderly with AF at high risk for stroke and bleeding and with comorbidities requiring polypharmacy, it is important to assess their safety and efficacy in this population.

Areas covered

We review changes in pharmacokinetics and pharmacodynamics observed with senescence and the effect on NOACs and drug and food interactions. We also provide an update on challenges related to NOAC use in situations that increases the risk for bleeding or require temporary discontinuation and address practical issues in the elderly AF patients managed on NOACs. Clinical studies and trials with cardiovascular outcomes reported from January 1990 to August 2020 were identified through the Medline database using PubMed, Cochrane Library, and EMBASE database.

Expert opinion

NOACs are highly effective in preventing stroke in AF patients with non-inferior or superior efficacy to warfarin, with reduced risk of major bleeding. However, in the older-elderly, evidence comes mainly from observational studies or extrapolation from studies in populations with minimal functional limitations or comorbidities. The high upfront cost and out-of-pocket expense for copayment or deductibles also limit the use of this effective therapy in a substantial number of patients. The cost reduction may further improve long-term use for NOACs in stroke prevention in elderly patients with AF.

KEYWORDS:

• Atrial fibrillation
• elderly
• non-vitamin K antagonist oral anticoagulants
• stroke
• warfarin
• dabigatran
• rivaroxaban
• apixaban
• edoxaban
• drug-drug interaction
• bleeding

Article highlights

• The growing epidemic of atrial fibrillation with the aging of the population leads to an increasing risk of stroke and thromboembolism requiring preventive strategies to reduce this complication.

• NOACs are highly effective in preventing stroke in high risk AF patients with non-inferior or superior efficacy to warfarin.

• Compared to VKA the risk of major, life threatening, or intracranial bleed has been demonstrated to be lower with NOACs.

• The presence of impaired renal function, other aging-associated comorbidities, and the concomitant use of other drugs affecting transport and metabolism of NOACs can all increase the risk of bleeding or reduce the efficacy of NOACs.

• The lack of point-of-care test for level of anticoagulation with NOACs may delay decision regarding emergent surgery or need for reversal in conditions with life-threatening bleeding.

• Specific antidotes that rapidly reverse anticoagulation are available, but access is limited.

• Patient education for those on any OAC is essential. Bleeding risk, possible side effects, drug/food interactions, and consequences of non-compliance need to be discussed. Patients should be advised to carry information about their anticoagulant therapy: dose, timing, and concomitant drugs used.

Acknowledgments

The authors thank Susan Nord, Jennifer Pfaff, Brian Miller and Brian Schurrer of Aurora Cardiovascular and Thoracic Services for editorial and graphics preparation of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.