Protocol, rationale and design of DAbigatran for Stroke PreVention In Atrial Fibrillation in MoDerate or Severe Mitral Stenosis (DAVID-MS): a randomised, open-label study

Mi Zhou, Esther W Chan, Jo Jo Hai, Chun Ka Wong, Yuk Ming Lau, Duo Huang, Cheung Chi Lam, Chor Cheung Frankie Tam, Yiu Tung Anthony Wong, See Yue Arthur Yung, Ki Wan Kelvin Chan, Yingqing Feng, Ning Tan, Ji-Yan Chen, Chi Yui Yung, Kwok Lun Lee, Chun Wai Choi, Ho Lam, Andrew Ng, Katherine Fan, Man Hong Jim, Kai Hang Yiu, Bryan P Yan, Chung Wah Siu, Mi Zhou, Esther W Chan, Jo Jo Hai, Chun Ka Wong, Yuk Ming Lau, Duo Huang, Cheung Chi Lam, Chor Cheung Frankie Tam, Yiu Tung Anthony Wong, See Yue Arthur Yung, Ki Wan Kelvin Chan, Yingqing Feng, Ning Tan, Ji-Yan Chen, Chi Yui Yung, Kwok Lun Lee, Chun Wai Choi, Ho Lam, Andrew Ng, Katherine Fan, Man Hong Jim, Kai Hang Yiu, Bryan P Yan, Chung Wah Siu

Abstract

Introduction: Current international guidelines recommend non-vitamin K oral anticoagulants (NOACs) for stroke prevention among patients with non-valvular atrial fibrillation (AF) at significant ischaemic stroke risk given the superior safety and comparable efficacy of NOACs over warfarin. Nonetheless, the safety and effectiveness of NOACs have not been evaluated in patients with AF with underlying moderate or severe mitral stenosis (MS), hence the recommended stroke prevention strategy remains warfarin therapy.

Method and analysis: MS remains disproportionately prevalent in Asian countries compared with the developed countries. This prospective, randomised, open-label trial with blinded endpoint adjudication aims to evaluate the safety and efficacy of dabigatran for stroke prevention in AF patients with moderate or severe MS. Patients with AF aged ≥18 years with moderate or severe MS not planned for valvular intervention in the coming 12 months will be randomised in a 1:1 ratio to receive dabigatran 110 mg or 150 mg two times per day or warfarin with international normalised ratio 2-3 in an open-label design. Patients with estimated creatinine clearance <30 mL/min, or with a concomitant indication for antiplatelet therapy will be excluded. The primary outcome is a composite of stroke and systemic embolism. Secondary outcomes are ischaemic stroke, systemic embolism, haemorrhagic stroke, intracranial haemorrhage, major bleeding and death. The estimated required sample size is approximately 686 participants.

Ethics and dissemination: The study protocol has been approved by the Institutional Review Board of the University of Hong Kong and Hong Kong West Cluster, Hospital Authority, Hong Kong for Fung Yiu King Hospital, Grantham Hospital, Queen Mary Hospital and Tung Wah Hospital in Hong Kong. Results will be published in peer-reviewed journals.

Trial registration number: ClinicalTrials.gov Registry (NCT04045093); pre-results.

Keywords: adult cardiology; clinical pharmacology; valvular heart disease.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Design of the DAVID-MS Study. BD, two times per day; DAVID-MS, DAbigatran for Stroke PreVention In Atrial Fibrillation in MoDerate or Severe Mitral Stenosis; INR, international normalised ratio; TTR, time in therapeutic range.
Figure 2
Figure 2
Four main groups of patients with AF requiring long-term anticoagulation therapy. AF, atrial fibrillation; MS, mitral stenosis; NOAC, non-vitamin K oral anticoagulant; VKA, vitamin K antagonist.

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