Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review
Open accessAbstract
Background Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke. Medical therapy for decreasing stroke risk involves anticoagulation, which may increase bleeding risk for certain patients. In determining the optimal therapy for stroke prevention for patients with AF, clinicians use tools with various clinical, imaging and patient characteristics to weigh stroke risk against therapy-associated bleeding risk. Aim This article reviews published literature and summarizes available risk stratification tools for stroke and bleeding prediction in patients with AF. Methods We searched for English-language studies in PubMed, Embase and the Cochrane Database of Systematic Reviews published between 1 January 2000 and 14 February 2018. Two reviewers screened citations for studies that examined tools for predicting thromboembolic and bleeding risks in patients with AF. Data regarding study design, patient characteristics, interventions, outcomes, quality, and applicability were extracted. Results Sixty-one studies were relevant to predicting thromboembolic risk and 38 to predicting bleeding risk. Data suggest that CHADS2, CHA2DS2-VASc and the age, biomarkers, and clinical history (ABC) risk scores have the best evidence for predicting thromboembolic risk (moderate strength of evidence for limited prediction ability of each score) and that HAS-BLED has the best evidence for predicting bleeding risk (moderate strength of evidence). Limitations Studies were heterogeneous in methodology and populations of interest, setting, interventions and outcomes analysed. Conclusion CHADS2, CHA2DS2-VASc and ABC scores have the best prediction for stroke events, and HAS-BLED provides the best prediction for bleeding risk. Future studies should define the role of imaging tools and biomarkers in enhancing the accuracy of risk prediction tools. Primary Funding Source Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999)
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Compared with the general population, patients with diabetes have an increased risk of both sudden cardiac death and non-sudden cardiac death.
“Compared with the general population, patients with diabetes have an increased risk of both SCD and non-SCD.575,615,[644][645][646]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [644]
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Beyond the 2020 guidelines on atrial fibrillation of the European society of cardiology
Boriani, G., Vitolo, M., Lane, D. A., Potpara, T., & Lip, G. Y. H. (2021) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2021.01.006 · Cited by 58 · see citing works
Stroke prevention strategies in high-risk patients with atrial fibrillation
Kotalczyk, A., Mazurek, M., Kalarus, Z. F., Potpara, T., & Lip, G. Y. H. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00459-3 · Cited by 60 · see citing works
Proietti, M., Lane, D. A., Boriani, G., & Lip, G. Y. H. (2019) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2019.02.009 · Cited by 55 · see citing works
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Nielsen, P. B., & Overvad, T. F. (2020) · Thrombosis and Haemostasis · doi:10.1055/s-0040-1710014 · Cited by 51 · see citing works
Atrial Fibrillation and Stroke
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Relationship between multimorbidity and outcomes in atrial fibrillation
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2025 Clinical practice guidelines for Atrial fibrillation and flutter
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Chao, T., Chan, Y., Chiang, C., Tuan, T., Liao, J., Chen, T., Lip, G. Y. H., & Chen, S. (2021) · Clinical Research in Cardiology · doi:10.1007/s00392-021-01816-z · Cited by 35 · see citing works
Recommendations from the ICM-VTE: General
Delegates, T. I.-V. G. (2022) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.21.01531 · Cited by 36 · see citing works
Stroke and bleeding risk stratification in atrial fibrillation: a critical appraisal
Lane, D. A., & Lip, G. Y. H. (2020) · European Heart Journal Supplements · doi:10.1093/eurheartj/suaa178 · Cited by 32 · see citing works
Zhang, J., Lenarczyk, R., Marín, F. R., Małaczyńska-Rajpold, K., Kosiuk, J., Doehner, W., Gelder, I. C. V., Lee, G., Hendriks, J., Lip, G. Y. H., et al. (2020) · EP Europace · doi:10.1093/europace/euaa358 · Cited by 32 · see citing works
Proietti, M., Romiti, G. F., Vitolo, M., Potpara, T., Boriani, G., Lip, G. Y. H., ESC-EHRA EORP-AF Long-Term General Registry Investigators, Boriani, G., Lip, G. Y. H., Tavazzi, L., et al. (2021) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcab069 · Cited by 31 · see citing works
Stroke prevention in atrial fibrillation
Lip, G. Y. H., Gue, Y. X., Zhang, J., Chao, T., Calkins, H. G., & Potpara, T. (2021) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2021.10.001 · Cited by 29 · see citing works
Management of cardiovascular complications of bruton tyrosine kinase inhibitors
Tang, C. P. S., Lip, G. Y. H., McCormack, T., Lyon, A. R., Hillmen, P., Iyengar, S., Martínez‐Calle, N., Parry‐Jones, N., Patten, P., Schuh, A., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17788 · Cited by 29 · see citing works
Peripheral Arterial Disease in Patients with Atrial Fibrillation: The AFFIRM Study
Vitalis, A., Shantsila, A., Proietti, M., Vohra, R. K., Kay, M., Olshansky, B., & Lip, G. Y. H. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2020.08.026 · Cited by 28 · see citing works
Hindricks, G., Potpara, T. S., Dagres, N., Arbelo, E., Bax, J. J., Blomström-Lundqvist, C., Boriani, G., Castellá, M., Dan, G., Dilaveris, P. E., et al. (2021) · Revista Española de Cardiología · doi:10.1016/j.recesp.2020.10.022 · Cited by 24 · see citing works
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Kwon, S., Lee, S., Choi, E., Lee, E., Jung, J., Han, K., Cha, M., Oh, S., & Lip, G. Y. H. (2021) · Stroke · doi:10.1161/strokeaha.120.030761 · Cited by 25 · see citing works
Nopp, S., Spielvogel, C. P., Schmaldienst, S., Klauser‐Braun, R., Lorenz, M., Bauer, B. N., Pabinger, I., Säemann, M. D., Königsbrügge, O., & Ay, C. (2022) · Thrombosis and Haemostasis · doi:10.1055/a-1754-7551 · Cited by 24 · see citing works
Taha, A., Nielsen, S. J., Franzén, S., Rezk, M., Ahlsson, A., Friberg, L., Björck, S., Jeppsson, A., & Bergfeldt, L. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.024703 · Cited by 23 · see citing works
Hammoudeh, A. J., Khader, Y. S., Kadri, N., Al-Mousa, E. N., Badaineh, Y., Habahbeh, L., Tabbalat, R. A., Janabi, H., & Alhaddad, I. A. (2021) · International Journal of Vascular Medicine · doi:10.1155/2021/5515089 · Cited by 22 · see citing works
Chao, T., Chan, Y., Tuan, T., Liao, J., Chen, T., Lip, G. Y. H., & Chen, S. (2021) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcab050 · Cited by 22 · see citing works
Garay, A., Formiga, F., Raposeiras‐Roubín, S., Abu-Assi, E., Sánchez‐Salado, J. C., Lorente, V., Alegre, O., Henriques, J. P. S., D’Ascenzo, F., Saucedo, J., et al. (2018) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1635259 · Cited by 22 · see citing works
Lane, D. A., Andrade, J. G., Arbelo, E., Boriani, G., Hendriks, J., Lee, S., Lip, G. Y. H., Mant, J., & Middeldorp, M. E. (2026) · The Lancet · doi:10.1016/s0140-6736(25)02166-x · Cited by 21 · see citing works
Pastori, D., Marang, A., Bisson, A., Herbert, J., Lip, G. Y. H., & Fauchier, L. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.026388 · Cited by 21 · see citing works
Bernardini, A., Bindini, L., Antonucci, E., Berteotti, M., Giusti, B., Testa, S., Palareti, G., Poli, D., Frasconi, P., & Marcucci, R. (2024) · International Journal of Cardiology · doi:10.1016/j.ijcard.2024.132088 · Cited by 21 · see citing works
Falsetti, L., Rucco, M., Proietti, M., Viticchi, G., Zaccone, V., Scarponi, M., Giovenali, L., Moroncini, G., Nitti, C., & Salvi, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-97218-2 · Cited by 20 · see citing works
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Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19
Caro‐Codón, J., Lip, G. Y. H., Rey, J. R., Iniesta, Á. M., Rosillo, S. O., Castrejón‐Castrejón, S., Rodríguez‐Sotelo, L., García‐Veas, J. M., Clement, I. M., Martinez, L. A., et al. (2021) · EP Europace · doi:10.1093/europace/euab015 · Cited by 20 · see citing works
Stroke in Patients with Atrial Fibrillation: Epidemiology, Screening, and Prognosis
Suomalainen, O., Martinez‐Majander, N., Broman, J., Mannismäki, L., Aro, A. L., Curtze, S., Pakarinen, S., Lehto, M., & Jukka Putaala, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm13010030 · Cited by 20 · see citing works
Domek, M., Gumprecht, J. J., Mazurek, M., Chao, T., & Lip, G. Y. H. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000750 · Cited by 19 · see citing works
Hazarapetyan, L., Zelveian, P., & Grigoryan, S. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s429892 · Cited by 18 · see citing works
Corica, B., Romiti, G. F., Mei, D. A., Proietti, M., Zhang, H., Guo, Y., Lip, G. Y. H., & on behalf of the mAF-App II trial investigators (2024) · Journal of General Internal Medicine · doi:10.1007/s11606-024-09037-6 · Cited by 19 · see citing works
Direct Oral Anticoagulant Use in Older Adults with Atrial Fibrillation: Challenges and Solutions
Bhandari, M., Pradhan, A. K., Vishwakarma, P., Renzo, L. D., Iellamo, F., Ali, W., & Perrone, M. A. (2025) · European Cardiology Review · doi:10.15420/ecr.2024.17 · Cited by 16 · see citing works
Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding
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Bleeding in anticoagulated patients with atrial fibrillation: practical considerations
Undas, A., Drabik, L., & Potpara, T. (2020) · Kardiologia Polska · doi:10.33963/kp.15205 · Cited by 21 · see citing works
Brundel, B. J. J. M., Ai, X., Hills, M. T., Kuipers, M. F., Lip, G. Y. H., & de Groot, N. M. S. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.17 · Cited by 17 · see citing works
Esteve‐Pastor, M. A., Rivera‐Caravaca, J. M., Roldán, V., Sanmartı́n, M., Arribas, F., Masjuán, J., Barrios, V., Cosı́n-Sales, J., Freixa‐Pamias, R., Recalde, E., et al. (2022) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvac060 · Cited by 16 · see citing works
Shang, L., Zhang, L., Guo, Y., Sun, H., Zhang, X., Bo, Y., Zhou, X., & Tang, B. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.682538 · Cited by 15 · see citing works
Güner, A., Kalçık, M., Gündüz, S., Gürsoy, M. O., Güner, E. G., Ulutaş, A. E., Kalkan, S., Onan, B., Bayam, E. M., Ertük, M., et al. (2020) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-020-02291-5 · Cited by 14 · see citing works
Askarinejad, A., Lane, D. A., Sadeghipour, P., Haghjoo, M., & Lip, G. Y. H. (2025) · European Journal of Clinical Investigation · doi:10.1111/eci.70082 · Cited by 14 · see citing works
Akbulut, A. C., Arisz, R. A., Baaten, C. C. F. M. J., Baidildinova, G., Barakzie, A., Bauersachs, R. M., ten Berg, J. M., van den Broek, W. W. A., de Boer, H. C., Bonifay, A., et al. (2023) · Thrombosis and Haemostasis · doi:10.1055/a-2052-9175 · Cited by 22 · see citing works
Ткачева, О. Н., Vorobyeva, N. M., Kotovskaya, Y. V., Рунихина, Н. К., Strazhesko, I. D., Вадимовна, В. С., Drapkina, O. M., Komarov, A. L., Orlova, Y. A., Панченко, Е. П., et al. (2021) · CARDIOVASCULAR THERAPY AND PREVENTION · doi:10.15829/1728-8800-2021-2847 · Cited by 14 · see citing works
Liu, X., Wang, S., He, W., & Guo, L. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1042763 · Cited by 13 · see citing works
Renal Disease and Atrial Fibrillation
Stefil, M., Nabrdalik, K., & Lip, G. Y. H. (2021) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2020.11.001 · Cited by 13 · see citing works
Kwon, S., Kim, T. J., Choi, E., Ahn, H., Lee, E., Lee, S., Ko, S., Oh, S., & Lip, G. Y. H. (2021) · Heart Rhythm · doi:10.1016/j.hrthm.2021.01.016 · Cited by 13 · see citing works
Hjelholt, T. J., Johnsen, S. P., Brynningsen, P. K., & Pedersen, A. B. (2020) · Journal of the American Geriatrics Society · doi:10.1111/jgs.16452 · Cited by 13 · see citing works
Thrombosis and Haemostasis 2018 Editor's Choice Papers
Weber, C., & Lip, G. Y. H. (2018) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1676653 · Cited by 13 · see citing works
Left atrial appendage amputation concomitant with cardiac surgery in patients with sinus rhythm
Gerçek, M., Börgermann, J., Gerçek, M., & Gummert, J. F. (2023) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezad088 · Cited by 12 · see citing works
Gue, Y. X., Bloomfield, D., Freedholm, D., & Lip, G. Y. H. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13082277 · Cited by 12 · see citing works
Lam, S. H. M., Romiti, G. F., Corica, B., Bucci, T., Olshansky, B., Chao, T.-F., Huisman, M. V., & Lip, G. Y. H. (2025) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvaf031 · Cited by 12 · see citing works
Maciorowska, M., Uziębło‐Życzkowska, B., Gorczyca-Głowacka, I., Wożakowska−Kapłon, B., Jelonek, O. E., Wójcik, M., Błaszczyk, R. T., Kapłon‐Cieślicka, A., Gawalko, M. M., Tokarek, T., et al. (2024) · Kardiologia Polska · doi:10.33963/v.kp.98356 · Cited by 11 · see citing works
New-onset atrial fibrillation after coronary surgery and stroke risk: a nationwide cohort study
Taha, A., Martinsson, A., Nielsen, S. J., Rezk, M., Pivodic, A., Guðbjartsson, T., Herrmann, F. E. M., Bergfeldt, L., & Jeppsson, A. (2024) · Heart · doi:10.1136/heartjnl-2024-324573 · Cited by 11 · see citing works
Rivera‐Caravaca, J. M., Esteve‐Pastor, M. A., Camelo-Castillo, A. J., Ramírez-Macías, I., Lip, G. Y. H., Roldán, V., & Marín, F. R. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1789099 · Cited by 11 · see citing works
Tonko, J., & Wright, M. J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173922 · Cited by 12 · see citing works
SCHRICKEL, J. W., Beiert, T., Linhart, M., Luetkens, J. A., Schmitz, J., Schmid, M. C., Hindricks, G., Arentz, T., Stellbrink, C., Deneke, T., et al. (2023) · Clinical Research in Cardiology · doi:10.1007/s00392-023-02319-9 · Cited by 10 · see citing works
Anticoagulation in Chronic Kidney Disease
Montomoli, M., Candia, B. G., Barrios, A. A., & Pérez-Bernat, E. (2024) · Drugs · doi:10.1007/s40265-024-02077-6 · Cited by 10 · see citing works
Catalani, F., Campello, E., Occhipinti, G., Zorzi, A., Sartori, M., Zanforlini, B. M., Franchin, A., Simioni, P., & Sergi, G. (2023) · Internal and Emergency Medicine · doi:10.1007/s11739-023-03375-9 · Cited by 10 · see citing works
- Authors
- Borre, E., Goode, A., Raitz, G., Shah, B., Lowenstern, A., Chatterjee, R., Sharan, L., Allen LaPointe, N., Yapa, R., Davis, J., Lallinger, K., Schmidt, R., Kosinski, A., Al-Khatib, S., & Sanders, G.
- Affiliations
- Duke University (US)
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States
- University of Colorado Anschutz (US)
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States
- Corresponding author
- Sanders, Gillian
- ORCID
- Venue
- Thrombosis and Haemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2018-10-30
- Volume
- 118
- Issue
- 12
- Pages
- 2171-2187
- ISSN
- 0340-6245 (ISSN-L)
- 2567-689X
- PMC
- PMC6754740
- OpenAlex
- W2899484044
- Cited by
- 229
- References
- 145
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 30 · 2023: 26 · 2022: 31 · 2021: 44 · 2020: 38 · 2019: 26 · 2018: 4 · 2017: 1 · 2016: 1
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Patient-Centered Outcomes Research Institute
- National Institutes of Health (5t32hl069749-20)
- Agency for Healthcare Research and Quality
- National Heart, Lung, and Blood Institute (T32-HL069749)
- National Institute of General Medical Sciences (T32GM007171)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- non-valvular atrial fibrillation, stroke risk prediction, bleeding risk prediction, thromboembolic risk, risk stratification tools, HAS-BLED score, VASc score, anticoagulation, stroke prevention
- MeSH terms
- Atrial Fibrillation, Blood Coagulation, Hemorrhage, Humans, Risk, Thromboembolism, United States, Stroke
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