178 CHAPTER 9 INTRODUCTION In this last chapter, the most important findings of this thesis and their practical implications are described and put into perspective by returning to the case of Mrs. de Jong. Furthermore, suggestions for future research on non-vitamin K antagonist oral anticoagulant (NOAC) therapy in the underserved population of frail older patients with atrial fibrillation (AF) are provided. The FRAIL-AF randomised controlled trial (RCT), which is extensively described in this thesis, is one of the very few RCTs in frail older patients. This clearly highlights the paucity of evidence in frail older patients, while in real life these patients are often the most difficult to manage due to their often mutually reinforcing comorbidities and associated polypharmacy. In other words, we often know the least, scientifically, about patients we encounter the most as health professionals. Therefore, in the second part of this general discussion, the concept of the ‘inverse research law’ will be introduced; i.e. the availability of evidence and hence research efforts and fundings appear to be inversely related to the clinical problems where research is most needed to provide answers, a phenomenon also illustrated by the unexpected and remarkable findings of the FRAIL-AF RCT, the centrepiece publication of this thesis. Finally, a major message of this thesis (i.e. reverse the ‘inverse research law’) and some suggestions on how to achieve this are provided. MOST IMPORTANT FINDINGS OF THIS THESIS AND THEIR PRACTICAL IMPLICATIONS IN RELATION TO THE CASE OF MRS. DE JONG This thesis is about the management of AF, one of the most common cardiac conditions that has a major impact on healthcare, partly because the lifetime risk of AF is around 30% among people of Western ancestry.1 AF is mainly affecting older people with a prevalence rising to 17.8% in those aged 85 years and older.2 Since AF can at least be partly considered as accelerated ageing of the heart and since patients with AF who are not anticoagulated have an increased risk of an ischaemic stroke compared to patients without AF, it can be concluded that AF is much more than solely an arrhythmia.3 The latest ESC guidelines on AF therefore recommend a holistic approach for the management of AF called ‘Atrial Fibrillation Better Care (ABC) pathway’ where the A stands for ‘anticoagulation/avoid stroke’, the B for ‘better symptom management’, and the C for ‘cardiovascular and comorbidity optimisation’.4 Better symptom management has recently received a lot of attention following the findings of the EAST-AFNET 4 trial. This landmark RCT demonstrated that early rhythm control therapy aimed at restoring sinus rhythm, regardless of symptom severity, reduced the composite outcome of cardiovascular death, stroke, or hospitalisation with worsening of heart failure or acute coronary syndrome, compared to a more lenient strategy in which
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