Safety and efficacy of warfarin in patients aged 80 years or older with AF – subgroup analysis of BAFTA study.

Azmil Abdul-Rahim, University of Glasgow
Ying Xuan Gue, University of Liverpool
Stephanie Harrison, University of Liverpool
Professor Gregory Y.H. Lip, University of Liverpool

The use of oral anticoagulation (OAC) to prevent stroke in atrial fibrillation (AF) is a vital part of the management. The initiation of OAC should follow a patient-centered approach, guided by stroke (CHA2DS2-VASc score) and bleeding risk (HAS-BLED score). 1 Importantly, a high bleeding risk score should not be used as the sole reason to withhold anticoagulation. Instead people should be appropriately treated with OAC, monitored and also re-assessed to determine any changes in risks over time. Apart from a small proportion of patients who satisfy the few absolute contraindications, 1 most patients would have net clinical benefit with OAC. An integral component of both bleeding and stroke risk scores is age which highlights the significant dilemma faced by clinicians in weighing the risk and benefit of anticoagulation in the elderly population. Between the two spectrums of clear benefit and absolute contraindication to OAC, there lies a grey area where clinicians are unable to objectively weigh the risk and benefit of OAC.
The concern of both stroke and bleeding risk in this group of patients has brought about some novel solutions, one of which has recently been reported. The Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation (ELDERCARE-AF) study is a phase 3, multicentre, randomised, double-blind placebo-controlled exploring the use of low dose edoxaban (15mg once daily) in eligible patients who otherwise would have not been prescribed OAC in the context of AF. 2 Eligibility was defined as (1) 80 years of age or older, (2) CHADS2 score 2 or more and (3) inappropriate for therapeutic dose of Vitamin K antagonists (VKA) or at approved doses for one or more of the following reasons: a low creatinine clearance (15 to 30 ml per minute), a history of bleeding from a critical area or organ or gastrointestinal bleeding, low body weight (≤45 kg), continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs), or current use of an antiplatelet drug.
The lower dose of edoxaban has shown superiority in preventing stroke in these high-risk patients (2.3% vs 6.7%, P<0.001) with no significant increased risk of major bleeding (3.3% vs 1.8%, P=0.09), albeit with a significantly increased risk of GI bleeding (2.3% vs 0.8%). The aim of the current study is to compare warfarin and aspirin and bleeding and stroke outcomes for patients meeting the eligibility criteria of the ELDERCARE-AF study.

1. In a similar cohort of patients to the ELDERCARE-AF study, VKA remains superior to aspirin in terms of embolic outcomes but with significant increased bleeding rates.

In the Birmingham Atrial Fibrillation Treatment of the Aged Study (BAFTA), 973 patients aged 75 years or older were randomised to receive warfarin or aspirin in an open-label study, to compare embolic and bleeding outcomes in elderly patients with AF. 3 Mean follow-up in the BAFTA study was 2.7 years. Lower risk of stroke, intracranial haemorrhage, or clinically significant arterial embolism was reported for participants receiving warfarin compared to participants receiving aspirin (Relative Risk 0·48, 95% Confidence Interval 0·28–0·80, p=0·003). Using patient-level data, we will extract a subset of patients fitting the eligibility criteria of the ELDERCARE-AF study.
With the subset of patients from BAFTA, we will use Cox-proportional hazard models to compare incident stroke and bleeding between warfarin and aspirin treatment. This will generate hazard ratios with 95% confidence intervals for stroke and bleeding outcomes in patients receiving warfarin or aspirin meeting the eligibility criteria for the ELDERCARE-AF study.

1. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. European Heart Journal. 2020.
2. Okumura K, Akao M, Yoshida T, et al. Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. N Engl J Med. 2020.
3. Mant J, Hobbs FR, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. The Lancet. 2007;370(9586):493-503.