The associated challenges of an ageing population for social welfare systems and individual healthy aging necessitate more research into effective prevention and rational treatment strategies. Besides the importance of identifying vulnerable elderly in an aging population to better outweigh benefits and risks of invasive procedures or potentially harmful medication, there remains a large knowledge gap in understanding the impact of age-related pharmacological changes and multimorbidity to the intended therapeutic value of several medications. This is particularly important for medicines for which the benefits need to be weighed against important associated risks, as with antithrombotics. Therefore, more fundamental research providing evidence to support the rational use of antithrombotics is needed. The overall aim of my PhD project proposal is to study rational antithrombotic use in terms of effectiveness and safe use in a real-life population with atrial fibrillation. By studying the use and impact of antithrombotic treatment in real-life multimorbid subjects with atrial fibrillation using different kinds of medication, we want to unravel the determinants of treatment success in terms of prevention of thromboembolisms and enhance insight in the optimal use of these drugs in terms of preventing (major) bleeding complications in the community population with comorbidities and polypharmacy.