optimum therapy for those with Atrial Fibrillation aFtEr Completing miTral valve repair surgery - The AFFECT trial

Research question: What is the optimum anticoagulation therapy for preventing thromboembolic and cardiovascular complications whilst minimising the risk of bleeding complications related to these, for patients with pre-existing atrial fibrillation following mitral valve repair surgery?

Background: There are no randomised trials to determine the optimum anticoagulant strategy to reduce thromboembolic and vascular complications whilst minimising bleeding risk after mitral valve repair (MVr) surgery. Direct Oral Anticoagulants (DOACS) are increasingly preferred to traditional oral anticoagulation with vitamin K antagonists (VKAs e.g. warfarin) but may not be as safe in all settings.

Large trials are urgently needed to inform national/international guidelines and clinical practice, which currently recommend the use of long-term VKAs e.g. warfarin in patients in permanent or persistent atrial fibrillation (AF) after surgery (Class IIa recommendation, Level of Evidence C). High rates of AF related complications, and thrombogenicity of the non-endothelialised repair prosthesis and sutures are cited as the rationale for this recommendation, but surveys of practice in the UK, and internationally, indicate that surgeon compliance with this guideline is low, less than 50%, highlighting a knowledge gap and resulting clinical uncertainty.

We aim to compare contemporary anticoagulant regimes to determine the optimal therapeutic strategy following MVr in those with pre-existing AF using an efficient, cost effective, inclusive trial design. The hypothesis is that DOACS are superior to VKA oral anticoagulants e.g. warfarin in reducing net clinical harm in these patients.

Methods: A multi-centre, prospective, open-label, superiority, randomised controlled trial in 1282 patients with pre-existing AF requiring oral anticoagulation after MVr surgery. Patients who have an indication for anticoagulation prior to surgery due to permanent AF, will receive either a DOAC or guideline mandated therapy of a VKA oral anticoagulant e.g. warfarin, for the duration of the trial (minimum of 1-year follow up for all patients, maximum of 48 months follow up).

Patients will be randomised 1:1, stratified by preoperative risk factors, AF ablation surgery, and AF related stroke risk. Follow up within trial will occur at 3 months and 1-year. Hospital Episode Statistics and Office for National Statistics data will be used for the primary outcome.

Aims and objectives: To compare contemporary anticoagulant regimes and establish the optimal therapeutic strategy following MVr for those with pre-existing AF. The primary clinical outcome is Net Clinical Harm (NCH), defined as a composite of all-cause mortality, major cardiovascular events, and major bleeding, and will be assessed for the duration of the study (minimum of 1-year follow up for all patients, maximum of 48 months follow up).

The primary economic outcome is cost effectiveness measured using incremental cost per quality-adjusted life year (QALY) gained based on responses to the EQ-5D-5L at 1-year post index MVr.

Timelines for delivery: The project will take 68 months, including an internal pilot phase with defined progression criteria.

Anticipated impact and dissemination: Findings will immediately impact NICE guidance in the UK, international guidelines and clinical practice, in an area with documented lack of evidence and significant variation in clinical practice and patient outcomes.