Stroke in Patients with Heart Failure – Where Are We Now?

Heart failure (HF) is a global burden which is associated with an increased risk of stroke and 10-24% of acute ischemic stroke patients suffer from chronic HF.^1,2 Moreover, it has been shown that the risk of stroke is higher in the first month after diagnosis of heart failure or after an episode of decompensated heart failure and is attenuated in the first 6 months after the acute event.^1,3,4 All three components of Virchow’s triad are present in HF (impaired blood flow, hypercoagulability, endothelial dysfunction), and therefore multiple studies have focused on antithrombotic therapies in HF to prevent stroke.^5,6

Apart from coronary artery disease and atrial fibrillation (AF) for which an antithrombotic indication has long been established, the results did not show benefits from initiating antithrombotic therapies in HF.^5,6  However, after an analysis of the study COMMANDER-HF, initiating anticoagulants in a sub-group of patients with HF and sinus rhythm (SR) did show some potential benefit.^3–5 COMPASS-HF is a more recent study which highlighted a similar concept.^3,5 Current HF guidelines mention that low-dose rivaroxaban may be considered in patients with HF with mid-range or preserved ejection fraction, with SR and coronary artery disease or peripheral artery disease, if the risk of stroke is high and there is a low bleeding risk.³

Interestingly, these results have brought attention to a new direction – identifying the group of HF patients at high risk of stroke. A large retrospective cohort study that included 15425 patients with HF and 28815 matched controls concluded that a lower ejection fraction was not associated with a higher risk of stroke. Other variables seemed to better predict the risk of stroke, including age, previous ischemic heart disease, previous stroke, hypertension, diabetes mellitus, the severity of heart failure symptoms and impaired kidney function.⁴ Most of these criteria are included in the CHA₂DS₂-VASc/R₂-CHA₂DS₂-VASc scores, which are used in AF patients to predict the risk of cardioembolic events. Consequently, new studies emerged by adding new parameters to these existing scores in order to predict stroke in HF, without AF.

A high BNP level seems to be a good predictor for occurrence of future stroke in HF patients⁷ and its addition to the existing scores seems to improve their performance.⁸ NT-proBNP has been shown as a valuable marker as well⁸ and data from large trials on patients with HF were collected to validate a new risk model – S₂I₂N_0-3, which includes stroke history, the use of insulin for diabetes and the level of NT-proBNP.⁹ By using this risk score, patients with reduced ejection fraction HF and SR were shown to have a similar incidence rate for stroke as patients with AF who do not receive anticoagulant treatment.⁹

How might this affect our clinical practice? A high level of NT-proBNP in stroke patients seems to be a great predictor of mortality over a 5-year follow-up period and this could be a consequence of the presence of HF and the additional risk that it carries.¹⁰ However,  other studies are needed to evaluate whether the assessment of this biomarker and of a specific cut-off point in our stroke patients could help us to detect HF and later refer them to receive optimal therapy, including SGLT2 inhibitors which are efficient in reducing major adverse cardiovascular events (including future stroke).^3,11,12 Furthermore, levels of NT-proBNP seem to be associated with AF-related stroke in HF and could be used to include patients with embolic stroke of undetermined source for cardiac rhythm monitoring.¹³

Finally, the dilemma of whether to use or not certain antithrombotic drugs in HF patients still exists. However, by identifying new markers and scores to predict stroke, we are now able to perform prospective studies in patients with HF at high risk of stroke and to better evaluate the benefits of antithrombotic therapies in such patients.

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1. Tai YH, Chang CC, Yeh CC, et al. Long-Term Risk of Stroke and Poststroke Outcomes in Patients with Heart Failure: Two Nationwide Studies. Clin Epidemiol. 2020;Volume 12:1235-1244. doi:10.2147/CLEP.S261179
2. Sanders CB, Knisely K, Rathfoot C, Edrissi C, Nathaniel T. Acute Ischemic Stroke and Heart Failure: Stroke Risk Factors Associated with Exclusion from Thrombolytic Therapy. Clin Appl Thromb. 2022;28:107602962211163. doi:10.1177/10760296221116347
3. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726. doi:10.1093/eurheartj/ehab368
4. Hjalmarsson C, Fu M, Zverkova Sandström T, et al. Risk of stroke in patients with heart failure and sinus rhythm: data from the Swedish Heart Failure Registry. ESC Heart Fail. 2021;8(1):85-94. doi:10.1002/ehf2.13091
5. Schäfer A, Flierl U, Bauersachs J. Anticoagulants for stroke prevention in heart failure with reduced ejection fraction. Clin Res Cardiol. 2022;111(1):1-13. doi:10.1007/s00392-021-01930-y
6. Barkhudaryan A, Doehner W, Scherbakov N. Ischemic Stroke and Heart Failure: Facts and Numbers. An Update. J Clin Med. 2021;10(5):1146. doi:10.3390/jcm10051146
7. Hotsuki Y, Sato Y, Yoshihisa A, et al. B‐type natriuretic peptide is associated with post‐discharge stroke in hospitalized patients with heart failure. ESC Heart Fail. 2020;7(5):2508-2515. doi:10.1002/ehf2.12818
8. Liu X, Abudukeremu A, Yu P, et al. Usefulness of B‐Type Natriuretic Peptide for Predicting the Risk of Stroke in Patients With Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2022;11(15):e024302. doi:10.1161/JAHA.121.024302
9. Kondo T, Abdul-Rahim AH, Talebi A, et al. Predicting stroke in heart failure and reduced ejection fraction without atrial fibrillation. Eur Heart J. 2022;43(42):4469-4479. doi:10.1093/eurheartj/ehac487
10. Hatab I, Kneihsl M, Bisping E, et al. The value of clinical routine blood biomarkers in predicting long-term mortality after stroke. Eur Stroke J. 2023;8(2):532-540. doi:10.1177/23969873231162125
11. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303
12. Gonzalez J, Bates BA, Setoguchi S, Gerhard T, Dave CV. Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction. Cardiovasc Diabetol. 2023;22(1):54. doi:10.1186/s12933-023-01784-w
13. Kneihsl M, Gattringer T, Bisping E, et al. Blood Biomarkers of Heart Failure and Hypercoagulation to Identify Atrial Fibrillation–Related Stroke. Stroke. 2019;50(8):2223-2226. doi:10.1161/STROKEAHA.119.025339