Management of patients with atrial fibrillation

This thesis is about the management of atrial fibrillation (AF), one of the most common cardiac conditions. AF mainly affects older people with a prevalence rising to 17.8% in those aged 85 years and older. AF can at least partly be considered as accelerated ageing of the heart that goes along with an increased risk of stroke, heart failure, and all-cause mortality compared to patients without AF. Therefore, it is evident that AF is more than just an arrhythmia. The latest European Society of Cardiology 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’. This thesis focuses on the A and C of the ABC pathway for the management of AF.

The most important finding of this thesis is that the FRAIL-AF randomised controlled trial (RCT) showed that switching from a vitamin K antagonist (VKA) to a non-VKA oral anticoagulant (NOAC) compared to continuing with a VKA in frail older patients with AF should not be considered without a clear indication, as switching leads to 69% more major or clinically relevant non-major bleeding. The FRAIL-AF trial is unique as it is the first randomised NOAC trial that exclusively included frail older AF patients. Thereby, this RCT provides important evidence that cannot be obtained from underpowered subgroup analyses of the pivotal NOAC trials that incorporated no or very low numbers of frail older patients, nor from observational data because of the inherent problem of bias due to residual confounding. The fact that the results of the FRAIL-AF trial showed an effect that turned out to be completely different from what was expected, underlines the importance of proper research using RCTs in frail older patients prior to uncritically generalising the findings of studies conducted in non-frail populations.

Another important finding of this thesis is that routine care data from the Julius General Practitioners’ Network showed that the prevalence of AF more than tripled from 0.4% in 2008 to 1.4% in 2017, most probably as a result of ageing of the population and increased awareness, detection and registration, particularly by general practitioners. Furthermore, a comprehensive systematic review and meta-analysis in this thesis showed that in AF patients receiving an off-label reduced NOAC dose (that is a reduced NOAC dose without a clear medical indication) compared to patients receiving an on-label non-reduced NOAC dose, bleeding risk nor all-cause mortality did not reduce with a hazard ratio (HR) of 1.10 (95% confidence interval (CI) 0.95-1.29) and 1.22 (95% CI 0.81-1.84), respectively. Finally, in an international multicentre cohort study of patients hospitalised with COVID-19 (CAPACITY-COVID), using a multivariable model with sex, age, and new-onset AF and/or atrial flutter (AFL), new-onset AF and/or AFL was associated with a two- to three-fold increased risk of in-hospital mortality in men aged 60-72 years, but not in women or in younger men.