For long, vitamin K antagonists (VKAs) were the only drug option to reduce the risk of stroke in patients with AF. VKAs are highly effective for reducing stroke risk, yet – due to interaction of VKAs with other drugs, nutritional status, and inter-current infections – dose-adjustments are frequently needed. Hence, both thrombotic events and bleeding events can occur. Both type of complications are more frequent in frail elderly patients with AF.
Since several years, an alternative has entered the clinical domain: non-VKA oral anticoagulants (NOACs). Large RCT demonstrated that NOACs are at least as effective as VKAs to reduce the risk of ischemic stroke, yet with a better safety profile (fewer intracranial bleeds). Frail elderly patients were not included in these RCTs, leaving a knowledge gap on the optimal choice of anticoagulant treatment in this increasing group of frail AF patients. This missing link will be addressed by this proposal using a pragmatic non-inferiority RCT design with 1 year of follow-up. Patients are recruited from i) existing infrastructure of three Dutch thrombosis services, ii) affiliated hospitals, and iii) nursing homes. We will randomize 2500 frail elderly AF patients to NOAC treatment (n=1250 index group), or usual VKA care (n=1250, control group). Inclusion criteria are a confirmed AF diagnosis, and age above 70 years plus frailty (defined as 2 or more positive items on the KATZ-ADL score). Exclusion criteria are severe renal impairment (eGFR < 30 ml/min/1.73m2) or valvular AF (NOACs contra-indicated in both groups). The composite primary outcome for this proposal will be thrombotic events and major or clinically relevant bleeds. We expect this outcome in those on a NOAC to be 8% versus 10% while on VKA and consider NOACs non-inferior to VKA if the one-sided 95% CI excludes an annual occurrence of 11%. Our proposal aims to answer the question whether NOACs are an alternative for usual VKA treatment in frail elderly AF patients.