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Atrial fibrillation (AF) is the most common heart rhythm disorder and mostly affects elderly people. The number of patients with AF will increase rapidly in the coming years, requiring organizational changes in the care for AF-patients. To improve care for patients with AF, multidisciplinary and coordinated care, so-called integrated care, has been recommended in the guidelines and showed beneficial effects in patients with newly diagnosed AF treated at experienced outpatient cardiology clinics. To investigate if integrated care for patients with AF could also be safely and effectively organized in primary care, we performed the ALL-IN cluster randomised trial. In 15 primary care practices randomised for the intervention arm, 527 patients provided informed consent for participating in the intervention, who were compared to 713 patients in the usual care arm. The integrated care intervention consisted of (i) quarterly check-ups for AF and its related comorbidities, (ii) anticoagulation monitoring by the primary care practice instead of the anticoagulation clinic, and (iii) close collaboration with anticoagulation clinics and cardiologists. The main finding after 2 years was a reduction in all-cause mortality of 45% in the intervention group compared to usual care (Chapter 2). Furthermore, we observed that the integrated care intervention in primary care reduced costs (ranging between -€760 to -€3868 per patient per 2 years) and also provided a small gain in Quality Adjusted Life Years between 0.00 and 0.06 (Chapter 3). The results of the ALL-IN trial support the view that AF is part of a systemic condition characterised by multiple interfering cardiovascular and non-cardiovascular comorbidities, requiring a broad, integrated approach. Therefore, organising integrated care for patients with AF in primary care offers an attractive solution for the increasing disease burden and healthcare costs associated with the increasing prevalence of AF. This thesis also entails observational studies on treatment with anticoagulants, which are often prescribed to patients with AF to prevent an ischaemic stroke. The downside of anticoagulant treatment is the increased risk of bleeding. Nowadays, anticoagulants called “NOACs” are preferred over the traditional vitamin K antagonists (VKAs). Concerns have emerged, however, that certain patients in routine practice receive a reduced NOAC dose without a clear indication, so-called ‘off-label dose reduction’. This likely occurs in an attempt to alleviate a presumed increased risk of bleeding, but possibly introduces an unnecessary risk of ischaemic stroke. We performed a systematic review and meta-analysis, showing that off-label dose reduction occurs in 15,7% of patients (Chapter 4). In a large observational study using data from routine clinical practice, we investigated the consequences of off-label dose reduction, and concluded that off-label dose reduction does not appear to decrease bleeding risk (Chapter 5). Finally, we investigated whether the number of concomitant drugs prescribed modifies the safety and effectiveness of NOACs compared to VKAs, using routine care data of 63.600 patients with AF. We concluded that major bleeding risk is comparable between NOACs and VKAs, regardless the number of concomitant drugs prescribed.