Abstract
Patients with atrial fibrillation (AF) have a five-fold increased risk for a stroke. Treatment with an oral anticoagulant reduces this risk with approximately 60%. Over the past decade, four non-vitamin K antagonist oral anticoagulants (NOACs) were introduced to the market. In this thesis, we performed a wide variety of studies
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on the introduction of the NOACs on the market and to further study the safety and effectiveness of NOACs in clinical practice.
In the Stockholm healthcare region, the regional clinical recommendations of having apixaban as the preferred NOAC, had a large influence on the prescribing of NOACs (chapter 2.1). Before the recommendation, all NOACs were used equally, while three months after the recommendation, apixaban was used four times more often compared to dabigatran and rivaroxaban combined. In patients initiated on antithrombotic therapy between March 2015 and February 2016, when NOACs were widely used in the Stockholm healthcare region, patients with high stroke and bleeding risks were more often prescribed low-dose aspirin or VKA treatment, instead of NOAC treatment, which is problematic given that aspirin treatment is less effective for stroke prevention (chapter 2.2). The introduction of NOACs was accompanied by an overall better antithrombotic treatment in the Stockholm Healthcare region (chapter 2.3). We found similar changes in treatment when repeating this study simultaneously in Stockholm, Denmark, Scotland, and Norway (chapter 2.4). In the Stockholm Healthcare region, in patients with AF newly initiated with NOAC treatment, 70% was persistent after five years of follow-up, and 85% were on treatment during follow-up when including restarters (chapter 2.5). Persistence and adherence were also high in five Western European healthcare settings (Stockholm, Denmark, Norway, Scotland, and Germany) (chapter 2.6).
In patients with AF at a moderate stroke risk, we found that NOAC treatment had a positive net clinical benefit compared to VKA treatment and no treatment in patients from Stockholm, Denmark, Norway, and Scotland (chapter 3.1). In patients with AF from Stockholm, treated with either a VKA or a NOAC, there was a significantly increased bleeding risk in patients using concomitant antidepressant therapy (HR: 1.42; CI: 1.12-1.80), but not a significantly increased stroke risk (HR: 1.23; CI: 0.93-1.62) compared to patients without concomitant antidepressant use (chapter 3.2). . In patients with AF receiving NOAC therapy from Stockholm, Denmark, and the Netherlands, there was a reduced risk for upper GIB when using concomitant PPI therapy (incidence rate ratio (IRR): 0.75; CI: 0.59-0.95) (chapter 3.3). In patients with AF, the 90-day mortality after an ischemic stroke, an intracranial haemmorhage or gastrointestinal bleed were high in the Stockholm Healthcare region; 25.1% after an ischemic stroke, 31.6% after an intracranial haemmorhageand 16.2% after a gastrointestinal bleed(16.2%) (chapter 3.4). Patients receiving VKA treatment at the time of the intracranial haemmorhage had a higher risk of dying compared to patients receiving NOAC treatment (HR: 1.36; CI: 1.04-1.78)
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