ESC 2022: What Current Insights Say About the Role of Dabigatran in Stroke Prevention with Atrial Fibrillation and Comorbidities

AF and Stroke Prevention

ESC Guidelines [1] for the management of AF recommend the ABC approach – anticoagulation (as stroke prevention), better symptom control (B), and management of comorbidities/CV risk factors (C). 

In stroke prevention for patients with AF, direct oral anticoagulants (DOACs) are generally recommended over vitamin K antagonists (VKAs; warfarin). DOACs are generally recommended as first-line treatment in AF management (recommendation strength Ia). Similar outcomes in all-cause mortality or cardiovascular (CV) mortality were observed in pivotal randomized controlled trials (RCTs) when comparing any DOAC with VKA.

Data from Practice

Professor Elaine Hylek from Boston University presented prospective data from the international GLORIA-AF registry, as detailed in another article, published in 2021. This registry collects data on patients newly diagnosed with AF between 2014 and 2016, aiming to assess the effectiveness and safety of anticoagulant therapy in real-world clinical practice. It shows that comorbidities are common among AF patients – out of over 21,000 patients in the registry, 71.2% had at least 2 concomitant chronic conditions [2]. AF and heart failure, type 2 diabetes, or chronic kidney disease share similar risk factors and often coexist, each affecting cardiovascular (CV) morbidity and mortality. 

AF and Heart Failure

Professor José Ramon González Juanatey from the University Hospital in Santiago de Compostela highlighted that due to the similar pathophysiology of AF and heart failure (HF), patients with one of these conditions have an increased risk of developing the other. AF can cause HF decompensation or be the primary trigger for HF development. Management priorities for both conditions overlap. DOACs are recommended over VKAs for patients with concurrent AF and HF [1].

In an analysis of data from the international GARFIELD-AF registry focusing on predictors of early mortality (within 1 month) from any cause in patients newly diagnosed with AF, chronic heart failure was an independent predictor of higher early mortality risk (hazard ratio [HR] 2.8), while initial anticoagulant therapy reduced this risk (DOACs: HR 0.31; VKAs: HR 0.51) [3].

Evidence from RCTs (RE-LY study) and real-world practice (GLORIA-AF registry) indicates that the advantageous safety and efficacy profile of both dabigatran doses compared to warfarin is consistent in AF patients, whether they have concomitant heart failure or not [4,5].

AF and Diabetes

Professor Jan Steffel from the University of Zurich noted that atrial structural remodeling is a significant impact of AF related to diabetes. Diabetes increases the risk of AF by promoting structural, electromechanical, and autonomic nervous system changes. The RE-LY study results demonstrated a consistent safety and efficacy profile for dabigatran compared to warfarin in patients with diabetes mellitus 2 (DM2) and without diabetes [6]. The RE-DUAL PCI study showed that the safety and efficacy of both dabigatran doses are consistent in AF patients with and without DM2 who underwent percutaneous coronary intervention (PCI) [7].

AF and Kidney Damage

Kidney damage in AF patients increases the risk of stroke and bleeding, as emphasized by Dr. John Eikelboom from McMaster University in Hamilton. The RE-LY study demonstrated that both dabigatran doses have a consistent safety and efficacy profile compared to warfarin in patients with mild to moderate renal impairment [7].

Eva Srbová
editorial team, proLékaře.cz

Sources:
1. Hindricks G., Potpara T., Dagres N. et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42 (5): 373–498, doi: 10.1093/eurheartj/ehaa612.
2. Kozieł M., Teutsch C., Halperin J. L. et al. Atrial fibrillation and comorbidities: clinical characteristics and antithrombotic treatment in GLORIA-AF. PLoS One 2021; 16: e0249524, doi: 10.1371/journal.pone.0249524.
3. Bassand J.-P., Virdone S., Goldhaber S. Z. et al. Early risks of death, stroke/systemic embolism, and major bleeding in patients with newly diagnosed atrial fibrillation. Circulation 2019; 139 (6): 787–798, doi: 10.1161/CIRCULATIONAHA.118.035012.
4. Ferreira J., Ezekowitz M. D., Connolly S. J. et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. Eur J Heart Fail 2013; 15 (9): 1053–1061, doi: 10.1093/eurjhf/hft111. 
5. Dubner S. J., Teutsch C., Huisman M. V. et al. Characteristics and 2-year outcomes of dabigatran treatment in patients with heart failure and atrial fibrillation: GLORIA-AF. ESC Heart Fail 2020; 7 (5): 2679–2689, doi: 10.1002/ehf2.12857.
6. Brambatti M., Darius H., Oldgren J. et al. Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: results from the RE-LY trial. Int J Cardiol 2015; 196: 127–131, doi: 10.1016/j.ijcard.2015.05.141. 
7. SPC Pradaxa. Available at: www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_cs.pdf
8. Hylek E. Introducing our patient with atrial fibrilation and multimorbidities. Atrial fibrilation and comorbidities: practical guidance for optimising stroke prevention. ESC Congress, Barcelona, 2022 Aug 27.
9. González Juanatey J. R. AF and heart failure: what do you need to know about NOACs? Atrial fibrilation and comorbidities: practical guidance for optimising stroke prevention. ESC Congress, Barcelona, 2022 Aug 27.
10. Steffel J. When complex conditions coexist: NOACs in diabetic patients. Atrial fibrilation and comorbidities: practical guidance for optimising stroke prevention. ESC Congress, Barcelona, 2022 Aug 27.
11. Eikelboom J. NOAC dosing criteria: applying guidelines to achieve the best outcomes. Atrial fibrilation and comorbidities: practical guidance for optimising stroke prevention. ESC Congress, Barcelona, 2022 Aug 27.