TREATS-AF:Educational intervention vs usual care on anticoagulation therapy control based on a SAMe-TT2R2 score-guided strategy

Anticoagulants ('blood thinners') are needed to prevent stroke and death in patients with atrial fibrillation (AF). AF is the world's most common form of irregular heartbeat, including in Thailand. Anticoagulation is a mainstay treatment in AF patients to prevent strokes occurring. Warfarin is the most commonly used anticoagulant in Thailand, but because it is influenced by many diet and patient factors it can be difficult to achieve good anticoagulation control. In Thailand, because of this, most patients receive inadequate control of their anticoagulation when using warfarin, leading to increased risk of stroke and death.
Our aim is to conduct a randomised-controlled trial (RCT) in Thai AF patients who have not used an anticoagulant before to evaluate the use of a simple clinical prediction score (SAMe-TT2R2) to help identify those patients likely to have a good response to anticoagulation with warfarin, compared with usual care. Predicted poorer responders (SAMe-TT2R2 >2) will be given an educational-behavioural intervention based on our previous RCT (TREAT trial) as an addition to routine care to improve their TTR on warfarin.
In this project, we will first undertake cultural adaptation of the TREAT intervention and translation, translation and validation of the patient knowledge questionnaire to ensure applicability to Thailand, and will include a qualitative study exploring patient satisfaction and acceptance of the TREAT approach and assess the impact on healthcare costs of this strategy. In addition, we would assess cost-effectiveness of the intervention in the Thailand healthcare system, and also explore composite clinical outcomes related to the intervention.
This study, if successful, will provide an inexpensive, easy approach that can be readily integrated into the existing Thai health service to improve the health of those patients with AF reducing both their risk of stroke and associated death. It will also give us an understanding of patients' perceptions of the treatment which we may be able to use to improve our approach. This collaborative study will also facilitate further research between the UK and Thailand and development of new patient-centred tools (e.g. Thai-version of TREAT educational intervention, Thai-language questionnaires, etc.).

The proposed research provides a major sustainable development in the management of patients in Thailand with atrial fibrillation (AF) who require life-long oral anticoagulation. We aim to conduct a prospective individually-randomised-controlled trial of warfarin-naïve Thai AF patients to evaluate the use of a clinical prediction score to stratify treatment modalities in relation to patient response to anticoagulation with warfarin.
Outcomes would be measured by the time in therapeutic range (TTR, primary outcome) compared with usual care. Second, we aim to assess the cost-effectiveness of an educational-behavioural intervention, to perform cross-cultural adaptation of the intervention and translation, validation of the translated patient knowledge questionnaire, and subsequent analysis. Third, we intend to perform a qualitative sub-study to investigate patient satisfaction and acceptance of this practical intervention to improve anticoagulation management. Finally, we will explore the cost-effectiveness of the intervention.
This study could potentially provide an inexpensive, easy and practical approach that can be readily integrated into the existing Thai health service to improve the health of those patients with AF, thus optimising anticoagulation management with warfarin, and reducing both their risk of stroke and associated death.
This unique collaboration would also facilitate development of novel patient-centred tools (e.g. Thai-version of the educational intervention, Thai-language questionnaires, etc.) that can be sustainably integrated into existing Thai healthcare services.
This proposal identifies a key approach to improve health and welfare by reducing the risk of complications arising from poor anticoagulation control (stroke/major bleeding) and will support capacity building in trial methodology helping develop the clinical research infrastructure beyond the proposed study.

Within the MRC document, Research Changes Lives: The MRC Strategic Plan 2014-2019, this project aligns with Strategic Aim 3 Going global: Accelerating progress in international health research (Global Health).

Atrial fibrillation (AF) is the commonest cardiac rhythm disorder worldwide, and confers a substantial risk of stroke and death (>10M/y). Importantly, strokes related to AF are more likely to be fatal or severely disabling. Oral anticoagulation is well established to reduce risk of stroke and death. Our work provides a new opportunity to improve the effectiveness of a widely used treatment and therefore reduce the number of strokes and deaths.

Our proposal facilitates improvements in healthcare systems to manage warfarin cost-effectively (with good quality anticoagulation control, as reflected by time in therapeutic range (TTR) >70%). Warfarin still remains a widely-used, excellent, cheap drug for stroke prevention globally, but needs regular review and assessment of TTR to ensure that good quality anticoagulation control is maintained.

Our use of a simple validated clinical prediction score (SAMe-TT2R2) to guide treatment decisions addresses the often asked question of how to identify AF patients likely to do well on warfarin, rather than a blanket 'NOAC for everyone' policy or a 'trial of warfarin' approach, with the latter leaving patients with suboptimal anticoagulation control (hence, putting such patients at excess risk of stroke/death) for the initial few months prior to a decision being taken about whether a NOAC can be prescribed.

Use of the SAMe-TT2R2 score is recommended in a European Society of Cardiology Working Group on Thrombosis Anticoagulation Task Force position document, as well as the NICE Implementation Collaborative for NOACs. Local health authorities in the United Kingdom have also incorporated the score into management and audit pathways for AF, e.g., the Warfarin Patient Safety audit tool. We have incorporated the SAMe-TT2R2 score as part of the 'Birmingham 3-step patient pathway', and it has been tested prospectively in the pilot mAFA trial conducted in China (PMID:28847546).

Ongoing studies have validated the SAMe-TT2R2 score in Asian populations, and given the increasing prevalence and incidence of AF this trial may offer a simple clinical-based strategy to improve anticoagulation management in Thailand, and to provide additional healthcare resources, including novel insights into Thai AF patient perceptions of this AF treatment in the TREAT intervention, as well as validation of patient-centred tools (e.g. Thai-version of TREAT educational intervention, Thai-language patient questionnaires, etc.).

This project will have impact because it takes a multidisciplinary approach to tackle a key health problem; how to improve stroke prevention in AF by optimising anticoagulation care. This management approach can be readily integrated within the current health service and ancillary outputs would facilitate research capacity building and development of novel patient-centred tools, initially impacting warfarin management of AF patients in Thailand, but could readily be applied to other low-and middle-income countries globally. Indeed, given the global burden of AF, these learnings are directly relevant to AF patients across the world.

In summary, the outcomes of this study have implications for the management of all patients receiving warfarin. Whilst the NOACs have sought to overcome the inherent difficulties experienced by patients prescribed warfarin, their cost has prohibited large-scale uptake especially in emerging economies. Thus, strategies to increase TTR and investment in pragmatic interventions that include optimisation of warfarin use that can aid current anticoagulation management are essential. This would include patient-centred approaches, including bespoke educational-behavioural interventions and validated questionnaires or educational materials (in Thai language).