14 CHAPTER 1 prescriptions in the community from 2008 to 2017. In Chapter 6 and 7, in-depth exploration was conducted through an RCT: the FRAIL-AF trial which aimed to evaluate the safety of switching from a VKA to a NOAC compared to continuing with a VKA in frail older patients with AF. In Chapter 6, the rationale and design of the FRAIL-AF trial were described and in Chapter 7 the results of this RCT were presented. Important in treatment with oral anticoagulation is determining the correct dose. Postmarketing observational studies show that some patients are treated with a reduced NOAC dose without a clear indication for dose reduction. In Chapter 8 a systematic review and meta-analysis on the clinical consequences of this so-called off-label reduced dosing of NOACs was described in patients with AF. In Chapter 9, the main findings of this thesis and their practical implications were described in relation to the case of Mrs. de Jong, unanswered questions in relation to the FRAIL-AF trial were provided and, most important, one of the main messages of this thesis was extensively discussed.
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