108 CHAPTER 7 daily practice, physicians will implicitly weigh multiple factors when deciding on the optimal anticoagulant treatment. This is very difficult to adjust for in observational studies.5,11 Monitoring through international normalised ratio (INR) testing allows for intervening at an early stage by titrating the VKA dose to the most optimal range, which may be beneficial in older patients living with frailty given their larger volatility in anticoagulant status. As a result, it is uncertain whether the superiority of NOACs over VKAs observed in patients with AF also holds for frail patients with AF, and the question whether these patients with AF taking a VKA should be switched to a NOAC remains heavily debated. We therefore performed the FRAIL-AF study, a pragmatic randomised multicentre open-label clinical trial in older patients with AF living with frailty. METHODS The data that support the findings of this study are available from the corresponding author on reasonable request. Trial design and oversight FRAIL-AF was a pragmatic, investigator-initiated, multicentre, open-label, randomised superiority trial. The protocol has been described previously.12 The trial was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht. The trial was conducted in accordance with the Declaration of Helsinki, Dutch law, and regulations related to clinical research. Written informed consent was provided by all study participants. The trial was registered at EudraCT (2017-000393- 11) and at The Netherlands Trial Registry: 6721 (FRAIL-AF study). Funding for the trial came from the Dutch government (ZonMw, grant number 848015004) with additional and unrestricted educational grants from BoehringerIngelheim, Bayer Healthcare, BMS Pfizer, and Daiichi Sankyo. The University Medical Center Utrecht also supported this trial via institutional funding. A patient representative was part of the steering committee. The full scientific committee, whose membership did not include representatives of financial contributors, had final responsibility for the interpretation of the data, the preparation of the manuscript, and the decision to submit for publication. An independent data safety monitoring board (DSMB), consisting of one cardiologist, one internal medicine specialist, and one biostatistician, had full access to accumulating study data and was deliberately left unblinded to randomisation status in order to fully assess patient safety in this frail population. The protocol allowed the DSMB to advice the trial steering committee on halting or modifying the trial if, in their view, the randomised comparison provided proof beyond reasonable doubt that one
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