88 CHAPTER 6 haemorrhage (about 50% risk reduction), also among older (usually above 75 years) patients included in these studies.7–12 Because of these advantages, NOACs are now recommended as the first choice anticoagulants for most patients with AF when initiating antithrombotic treatment. Moreover, guidelines even recommend to consider switching from VKA to NOAC treatment, especially if time in therapeutic range is not well controlled despite good drug adherence.13 Importantly, frail elderly were not included in the landmark NOAC randomised controlled trials. The evidence on the efficacy and safety of NOACs may not be generalisable to frail elderly with AF for a variety of reasons.14,15 To summarise, in frail elderly the dynamic pharmacokinetics have changed and as such this may be more ‘fragile’. It is likely that drug distribution is generally different due to altered body composition with relatively less muscle and more fatty tissue, and prolonged availability of drugs and their remnants because of lower elimination capacities of liver and kidney. In addition, cognitive impairment and interacting polypharmacy may negatively influence treatment adherence and persistence. NOACs lack control of anticoagulant status, as in VKAs with INR monitoring, which is a disadvantage if anticoagulant status is very volatile as may be the case in the large majority of frail elderly. Finally, notably in frail elderly due to changed pharmacokinetics, switching from VKA to NOAC treatment possibly induces a time frame in which patients are not yet fully eliminated of VKAs while NOACs are already initiated, thereby probably (temporarily) increasing bleeding risk. Altogether, there is currently clinical equipoise on which oral anticoagulant to use— VKAs or NOACs— in frail elderly patients who already comprise ±25% of all patients with AF, and this group is likely to increase in the near future.13 Importantly, there is even more uncertainty on whether or not frail elderly patients on VKA treatment should switch to a NOAC based regimen, given that general clinical practice data on safety and effectiveness of switching anticoagulant treatment is confounded by the reason to switch.16 Thus, there is an urgent need for evidence from randomised studies to assess whether frail elderly should switch from VKA to NOAC treatment. Therefore, we designed the FRAIL-AF study. The primary objective of the FRAIL-AF study is to determine whether switching from INR guided VKA management to a NOAC based treatment strategy reduces the risk of major or clinically relevant non-major (CRNM) bleeding complications compared with continuing INR guided VKA management in frail elderly patients with AF.
RkJQdWJsaXNoZXIy MTk4NDMw