Antithrombotic treatment of atrial fibrillation before and after the introduction of non-vitamin K antagonist oral anticoagulants (NOAC) in the Stockholm health care region

Atrial fibrillation (AF) is the most common cardiac arrhythmia and the major risk factor for thromboembolic stroke. Effective treatment with the oral anticoagulant (OAC) warfarin has been available for decades. However warfarin treatment is complicated, and demands dose adjustments and regular monitoring. Warfarin also increases the risk for bleeding, especially intracranial bleeding which is rare but often fatal. Undertreatment of AF with OACs has long been a global problem and it has been common to use low-dose aspirin (ASA) instead, despite evidence of poor efficacy.

Several new directly acting oral anticoagulants (NOACs) have been introduced in routine care based on promising results from randomised trials – the first being dabigatran in 2011, followed by rivaroxaban in 2012 and apixaban in 2013. The introduction of these drugs has brought hope of facilitating OAC treatment, increasing the proportion of patients treated, and possibly also improving the effectiveness and/or safety of treatment. This thesis is based on four population based epidemiological studies describing the antithrombotic treatment of AF before and after the introduction of NOACs in the Stockholm health care region using the health registry of the Stockholm health care region, Vårdanalysdatabasen (VAL).

Study I-II describe the entire AF population in the region, including demographics, risk stratification, treatment, and outcomes before the introduction of NOACs. Study III-IV compare treatment persistence, adherence, effectiveness, and safety of different antithrombotic treatments. The analyses show that undertreatment was common prior to the introduction of NOACs, but many of the patients without anticoagulant treatment were old, with complicating co-morbidities, high bleeding risk and a poor prognosis in addition to a high risk of ischemic stroke. With NOACs there was a dramatic increase in the number of AF patients in the registries and a substantially larger proportion of the patients received OAC treatment. NOACs now dominate new treatment initiations, while warfarin has decreased substantially. In routine care warfarin and apixaban was associated with better persistence than dabigatran or rivaroxaban. Adherence with OAC treatment was high (>90%), and slightly better with the once daily regimen of rivaroxaban than the twice daily regimens of apixaban and dabigatran. NOAC treatment had similar or better effectiveness and safety compared to warfarin treatment, with similar outcomes among the elderly (≥80 years) and patients with previous severe bleeds. NOACs were associated with fewer intracranial bleeds, but more gastrointestinal bleeds. The advantages with NOAC treatment were most pronounced with standard dosing in patients under the age of 80, and with reduced doses in patients aged 80 and above.

In conclusion, this thesis shows improvements in the management of AF in the Stockholm health care region and confirms that NOACs are attractive antithrombotic treatments for AF patients in routine care. More research is needed to further optimize the use of NOACs.

List of scientific papers

I. Forslund T, Wettermark B, Wandell P, von Euler M, Hasselstrom J, Hjemdahl P. Risk scoring and thromboprophylactic treatment of patients with atrial fibrillation with and without access to primary healthcare data: experience from the Stockholm health care system. Int J Cardiol. 2013;170:208-14.
https://doi.org/10.1016/j.ijcard.2013.10.063

II. Forslund T, Wettermark B, Wändell P, von Euler M, Hasselström J, Hjemdahl P. Risks for stroke and bleeding with warfarin or aspirin treatment in patients with atrial fibrillation at different CHA(2)DS(2)VASc scores: experience from the Stockholm region. Eur J Clin Pharmacol. 2014;70:1477-85.
https://doi.org/10.1007/s00228-014-1739-1

III. Forslund T, Wettermark B, Hjemdahl P. Comparison of treatment persistence with different oral anticoagulants in patients with atrial fibrillation. Eur J Clin Pharmacol. 2016;72:329-38.
https://doi.org/10.1007/s00228-015-1983-z

IV. Forslund T, Wettermark B, Andersen M, Hjemdahl P. Stroke and bleeding with NOAC or warfarin treatment in patients with non-valvular atrial fibrillation: a population based cohort study. Europace. 2017.
https://doi.org/10.1093/europace/euw416