Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score: A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy
Abstract
Oral anticoagulation (OAC) to prevent stroke has to be balanced against the potential harm of serious bleeding, especially intracranial haemorrhage (ICH). We determined the net clinical benefit (NCB) balancing effectiveness and safety of no antithrombotic therapy, aspirin and warfarin in AF patients with none or one stroke risk factor. Using Danish registries, we determined NCB using various definitions intrinsic to our cohort (Danish weights at 1 and 5 year follow-up), with risk weights which were derived from the hazard ratio (HR) of death following an event, relative to HR of death after ischaemic stroke. When aspirin was compared to no treatment, NCB was neutral or negative for both risk strata. For warfarin vs no treatment, NCB using Danish weights was neutral where no risk factors were present and using five years follow-up. For one stroke risk factor, NCB was positive for warfarin vs no treatment, for one year and five year follow-up. For warfarin vs aspirin use in patients with no risk factors, NCB was positive with one year follow-up, but neutral with five year follow-up. With one risk factor, NCB was generally positive for warfarin vs aspirin. In conclusion, we show a positive overall advantage (i.e. positive NCB) of effective stroke prevention with OAC, compared to no therapy or aspirin with one additional stroke risk factor, using Danish weights. 'Low risk' AF patients with no additional stroke risk factors (i.e.CHA2DS2-VASc 0 in males, 1 in females) do not derive…
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Rates of stroke and thromboembolism vary considerably in patients with CHA2DS2-VASc scores of 1 or 2 due to differences in outcomes, populations, and anticoagulation status.
“The rates of stroke and thromboembolism vary considerably in patients with CHA 2 DS 2 -VASc scores of 1 or 2 due to differences in outcomes, populations, and anticoagulation status (Web Addenda Table 1).371,376,377,1041”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [377]
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The ageing population is neglected in research studies of traumatic brain injury
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Li, Y., & Lip, G. Y. H. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.09.057 · Cited by 21 · see citing works
“A recent study from an Asian population, including 11,046 AF patients >90 years, showed that warfarin was associated with a lower risk of ischemic stroke and positive NCB[94].”
BackgroundInfluentialSelf-citationLip, G. Y. H., Potpara, T., Boriani, G., & Blomström‐Lundqvist, C. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12468 · Cited by 19 · see citing works
Self-citationAtrial Fibrillation in Patients With Hypertension
Lip, G. Y. H. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07901 · Cited by 19 · see citing works
“Even a single stroke risk factor confers risks of stroke and mortality, and oral anticoagulation confers a positive net clinical benefit compared with aspirin or no antithrombotic treatment.(8,9) Effective stroke prevention in AF means oral anticoagulation, whether as a vitamin K antagonist (eg, warfarin) or a non–vit…”
Self-citationStroke Prevention in Atrial Fibrillation
Voukalis, C., Shantsila, E., & Lip, G. Y. H. (2017) · The Journal of the Royal College of Physicians of Edinburgh · doi:10.4997/jrcpe.2017.105 · Cited by 18 · see citing works
Self-citationEmerging Tools for Stroke Prevention in Atrial Fibrillation
Voukalis, C., Lip, G. Y. H., & Shantsila, E. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.01.017 · Cited by 16 · see citing works
“Whilst there are variousways to defineNCB, it ismost commonly estimatedbybalancing the risk of ischemic stroke without OAC against the risk of intracranial haemorrhage with OAC (Lip et al., 2015).”
BackgroundSelf-citationPotpara, T., Dagres, N., Mujović, N. M., Vasić, D., Ašanin, M., Nedeljkovic, M. A., Marín, F. R., Fauchier, L., Blomström‐Lundqvist, C., & Lip, G. Y. H. (2016) · Advances in Therapy · doi:10.1007/s12325-016-0458-7 · Cited by 16 · see citing works
Self-citationDecision-making interventions to stop the global atrial fibrillation-related stroke tsunami
Cerasuolo, J. O., Montero‐Odasso, M., Ibáñez, A. M., Doocy, S., Lip, G. Y. H., & Sposato, L. A. (2017) · International Journal of Stroke · doi:10.1177/1747493016687579 · Cited by 17 · see citing works
“Contrarily, the net clinical benefit for aspirin is neutral.(18) Therefore, concordant with current guidelines, OACs are the treatment of choice for preventing ischemic stroke in high-risk AF patients (defined as having a CHA2DS2-VASc score of 2(19)) and in a considerable proportion with a single stroke risk factor (C…”
BackgroundSelf-citationEditors’ Choice 2016 papers in Thrombosis and Haemostasis
Lip, G. Y. H., & Weber, C. (2016) · Thrombosis and Haemostasis · doi:10.1160/th16-11-0899 · Cited by 14 · see citing works
“The journal also contributed to the debate on appropriate use of stroke risk scores, such as the CHA2DS2-VASc score – and whether OAC should be used in AF patients with bioprosthesis (23) or those with only one stroke risk factor, given the clearly positive net clinical benefit of OAC in such patients compared to aspi…”
Self-citationAdding Rigor to Stroke Rate Investigations in Patients With Atrial Fibrillation
Nielsen, P. B., & Lip, G. Y. H. (2017) · Circulation · doi:10.1161/circulationaha.116.025944 · Cited by 14 · see citing works
Self-citationRisk Stratification Models in Atrial Fibrillation
Shahid, F., & Lip, G. Y. H. (2017) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0036-1597285 · Cited by 13 · see citing works
Self-citationYeh, Y., Chan, Y., Chen, S., Chang, S., Wang, C., Kuo, C.-T., Lip, G. Y. H., Chen, S., & Chao, T. (2022) · The American Journal of Medicine · doi:10.1016/j.amjmed.2022.03.011 · Cited by 12 · see citing works
Self-citationTsai, C.-T., Chan, Y., Liao, J., Chen, T., Lip, G. Y. H., Chen, S.-A., & Chao, T. (2024) · BMC Medicine · doi:10.1186/s12916-024-03338-7 · Cited by 11 · see citing works
“The NCB with 95% confidence intervals (CI) were calculated from rate differences of ischemic stroke and ICH of the present study based on the weights previously produced and reported in the studies by Singer et al. [20], Connolly et al. [21], and Lip et al. [22].”
Self-citationLee, J., Joung, B., Cha, M., Lee, J. H., Lim, W., Kim, T., Shin, S. Y., Uhm, J., Lim, H. E., Kim, J., et al. (2018) · Korean Journal of Medicine · doi:10.3904/kjm.2018.93.2.87.e1 · Cited by 11 · see citing works
State of play and future direction with NOACs: An expert consensus
Cohen, A. T., Lip, G. Y. H., Caterina, R. D., Heidbüchel, H., Zamorano, J. L., Agnelli, G., Verheugt, F. W. A., & Camm, A. J. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.04.001 · Cited by 10 · see citing works
Self-citationTiili, P., Jukka Putaala, A., Mehtälä, J., Khanfir, H., Niiranen, J., Korhonen, P. A., Raatikainen, P. M. J., & Lehto, M. (2019) · Circulation Journal · doi:10.1253/circj.cj-18-0975 · Cited by 10 · see citing works
Shahid, F., Shantsila, E., & Lip, G. Y. H. (2016) · F1000Research · doi:10.12688/f1000research.10176.1 · Cited by 10 · see citing works
“In essence, patients with risk factors should be offered OAC unless contraindicated, given the positive net clinical benefit for treating such patients 6,10,11 .”
BackgroundInfluentialSelf-citationLee, J., Joung, B., Cha, M., Lee, J. H., Lim, W., Kim, T., Shin, S. Y., Uhm, J., Lim, H. E., Kim, J., et al. (2018) · Korean Journal of Medicine · doi:10.3904/kjm.2018.93.2.87 · Cited by 8 · see citing works
“하지만 연구마다 대상 환자군 과 항응고 치료 상태, 임상적 결과가 달리 설정되어 있어 상 당한 차이를 보이고 있어 신중한 해석이 필요하다[10,15-17].”
How to Manage Occult Atrial Fibrillation Detected on Long-Term Monitoring
Lip, G. Y. H. (2016) · Circulation · doi:10.1161/circulationaha.115.016797 · Cited by 7 · see citing works
“European Society of Cardiology (ESC) guideline recommendations.(21)”
Self-citationEscalas de evaluación del riesgo tromboembólico y hemorrágico en la fibrilación auricular
Copete, J. P., Esteve‐Pastor, M. A., Roldán, V., Valdés, M., & Marín, F. R. (2016) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(16)30011-5 · Cited by 7 · see citing works
Potpara, T., Lip, G. Y. H., Blomström‐Lundqvist, C., Chiang, C., & Camm, A. J. (2017) · The American Journal of Medicine · doi:10.1016/j.amjmed.2017.02.026 · Cited by 6 · see citing works
Self-citationFibrilación auricular: enfoque para el médico no cardiólogo
de Caldas, U., Forero, J., Moreno, J., del Bosque, U., Agudelo, C. A., Cayre, I. P. S., Rodríguez, E., de Manizales, I. D. C., & Sánchez, P. (2017) · IATREIA · doi:10.17533/udea.iatreia.v30n4a05 · Cited by 7 · see citing works
“, reportaron recientemente que solo el 5% de los pacientes con FA que consultaban a urgencias tenían INR en rango terapéutico (15), lo cual está en consonancia con la baja tasa de tiempo en rango terapéutico que se ha demostrado en pacientes participantes de estudios clínicos controlados (66% del tiempo en rango terap…”
BackgroundInfluentialSkjøth, F., & Nielsen, P. B. (2016) · Thrombosis and Haemostasis · doi:10.1160/th16-07-0523 · Cited by 6 · see citing works
Self-citationNet Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation
Polymeris, A. A., Branca, M., Sylaja, P. N., Sandset, E. C., de Sousa, D. A., Thomalla, G., Paciaroni, M., Gattringer, T., Strbian, D., Trelle, S., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.56307 · Cited by 5 · see citing works
Direct oral anticoagulant reversal: how, when and issues faced
Dzeshka, M. S., Pastori, D., & Lip, G. Y. H. (2017) · Expert Review of Hematology · doi:10.1080/17474086.2017.1379896 · Cited by 5 · see citing works
“The evidence, which supports initiation of OAC for prevention of stroke/systemic embolism in the presence of one or more additional CHA2DS2VASc stroke risk factors, is based on positive net clinical benefit of antithrombotic therapy against potential harm of serious bleeding [43,44].”
BackgroundSelf-citationJung, M., Byeon, K., Kang, K., Lee, W. S., Kim, S., Park, Y. M., Hwang, Y. M., Lee, S. H., Jin, E., Roh, S., et al. (2023) · Journal of Arrhythmia · doi:10.1002/joa3.12840 · Cited by 4 · see citing works
Self-citationDzeshka, M., Brown, R. A., Capodanno, D., & Lip, G. (2017) · Interventional Cardiology Clinics · doi:10.1016/j.iccl.2016.08.007 · Cited by 6 · see citing works
Self-citationManagement of atrial fibrillation: easy as ABC
Mahmood, M., & Lip, G. Y. H. (2019) · Minerva Medica · doi:10.23736/s0026-4806.18.05824-x · Cited by 5 · see citing works
Self-citationGrymonprez, M., Steurbaut, S., Sutter, A. D., & Lahousse, L. (2020) · Open Heart · doi:10.1136/openhrt-2020-001465 · Cited by 5 · see citing works
“12 15–178 10 Physicians should be aware of the beneficial role of NOACs in this patient subgroup, instead of awaiting anticoagulation initiation until at least two risk factors are present.”
Harrison, S. L., Akpan, A., & Lip, G. Y. H. (2021) · Journal of the American Geriatrics Society · doi:10.1111/jgs.17142 · Cited by 5 · see citing works
“The net clinical benefit of OACs compared with no treatment or aspirin is clear for most people with AF, apart from those at lowest stroke risk.(2) The common risk factors for incident AF are also risk factors for stroke and bleeding in AF.”
BackgroundSelf-citationRitchie, L. A., Harrison, S. L., Penson, P. E., Akbari, A., Torabi, F., Hollinghurst, J., Harris, D. E., Oke, O. B., Akpan, A., Halcox, J., et al. (2024) · Age and Ageing · doi:10.1093/ageing/afae021 · Cited by 4 · see citing works
Self-citationEditors’ Choice 2015 papers in Thrombosis and Haemostasis
Weber, C., & Lip, G. Y. H. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-11-0911 · Cited by 4 · see citing works
“showed positive overall advantage in terms of net clinical benefit for OAC even in patients with AF and one stroke risk factor (39).”
BackgroundSelf-citationLee, K. B., Kim, T., Park, J., Park, J., Kang, K., Kim, J., Park, H. W., Choi, E., Kim, J., Lee, Y. S., et al. (2022) · Yonsei Medical Journal · doi:10.3349/ymj.2022.63.4.317 · Cited by 4 · see citing works
Optimizing stroke prevention in elderly patients with atrial fibrillation
Lip, G. Y. H. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13480 · Cited by 4 · see citing works
Self-citationMisconceptions on Interpretation of Risk Prediction Tools in Atrial Fibrillation
Nielsen, P. B., Larsen, T. B., & Lip, G. Y. H. (2016) · The American Journal of Medicine · doi:10.1016/j.amjmed.2015.11.038 · Cited by 4 · see citing works
“Atrial fibrillation patients with one stroke risk factor (ie, CHA2DS2-VASc score of 1 in males or 2 in females) have a positive net clinical benefit from OAC treatment, while patients with a CHA2DS2-VASc score of 0 in males or 1 in females did not benefit from OAC or even aspirin, compared with no treatment.(4) In the…”
BackgroundSelf-citationVoukalis, C., & Lip, G. Y. H. (2017) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.02.010 · Cited by 4 · see citing works
Self-citationPotpara, T., & Olesen, J. B. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.12.076 · Cited by 4 · see citing works
Polymeris, A. A., Koga, M., Strbian, D., Adhiyaman, V., Krishnan, M., Branca, M., Horvath, T., Goeldlin, M. B., Shim, G. C., Gumbinger, C., et al. (2025) · Journal of Stroke · doi:10.5853/jos.2024.04322 · Cited by 3 · see citing works
“We additionally analyzed the net clinical benefit of antiplatelet use over non-use, adopting established methodology as in prior research, 12,13 with weighting of the type of events for their impact on death and disability relative to recurrent ischemic stroke or systemic embolism.”
InfluentialShahid, F., Shantsila, E., & Lip, G. Y. H. (2016) · European Heart Journal Supplements · doi:10.1093/eurheartj/suw049 · Cited by 3 · see citing works
Self-citationStroke prevention in atrial fibrillation: can we do better?
Lane, D. A., & Lip, G. Y. H. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.117 · Cited by 3 · see citing works
Self-citationShahid, F., Shantsila, E., & Lip, G. Y. H. (2016) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvv057 · Cited by 3 · see citing works
Self-citation2025 Thai guideline for the diagnosis and management of atrial fibrillation
Ngarmukos, T., Methavigul, K., Rungpradubvong, V., Apiyasawat, S., Wongcharoen, W., Pumprueg, S., Boonyapisit, W., Suwanagool, A., Chantrarat, T., Makarawate, P., et al. (2025) · Asian Biomedicine · doi:10.2478/abm-2025-0028 · Cited by 2 · see citing works
“Patients with an annual risk of ≥1% but 2% for ischemic stroke and thromboembolism should be considered for OAC, balancing the benefits of stroke and thromboembolism risk reduction versus the individual patient’s bleeding risk [29, 30].”
InfluentialThromboemboliás kockázat pitvarfibrillációban
Csanádi, Z. (2016) · Orvosi Hetilap · doi:10.1556/650.2016.30575 · Cited by 2 · see citing works
Nielsen, P. B., Potpara, T., & Lip, G. Y. H. (2018) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2018.07.003 · Cited by 2 · see citing works
Self-citationOkutucu, S. (2020) · The Anatolian Journal of Cardiology · doi:10.14744/anatoljcardiol.2020.17064 · Cited by 2 · see citing works
“equal weight, and the paroxysmal nature of the AF may be considered (18).”
Shahid, F., Lip, G. Y. H., & Shantsila, E. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.05.002 · Cited by 1 · see citing works
Self-citationStroke prevention in atrial fibrillation: Where are we now?
Lip, G. Y. H. (2015) · Indian Heart Journal · doi:10.1016/j.ihj.2015.11.002 · Cited by 1 · see citing works
“The net clinical benefit is also positive for OAC vs untreated or OAC vs aspirin; in contrast, the NCB is neutral/negative for aspirin vs untreated.(15)”
Self-citationBeneficios y riesgos de los anticoagulantes orales en la fibrilación auricular
Roldána, V., & Marín, F. R. (2019) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(19)30029-9 · Cited by 1 · see citing works
Optimizing prognosis in atrial fibrillation: A call to action in Portugal
Ferreira, J., António, N., Cortez‐Dias, N., Gonçalves, L. R., Sargento‐Freitas, J., HAFE, P. V., & Gil, V. M. (2020) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2020.07.011 · Cited by 1 · see citing works
Lip, G. Y. H. (2016) · Circulation · doi:10.1161/circulationaha.116.023663 · Cited by 1 · see citing works
“European Society of Cardiology (ESC) guideline recommendations.(21)”
BackgroundSelf-citationMazurek, M., & Lip, G. Y. H. (2017) · European Heart Journal Acute Cardiovascular Care · doi:10.1177/2048872616688455 · Cited by 1 · see citing works
Self-citationNielsen, P. B., Larsen, T. B., & Lip, G. Y. H. (2016) · Stroke · doi:10.1161/strokeaha.116.013672
Self-citationPotpara, T., Jokić, V., & Mijatovic, Z. (2016) · Srce i krvni sudovi · doi:10.5937/siks1601018p
Primärprävention und Sekundärprävention des Hirninfarkts
Ringelstein, E. B. (2020) · Springer Reference Medizin · doi:10.1007/978-3-662-60676-6_149
Risk Stratification in Atrial Fibrillation
Shahid, F., Dzeshka, M. S., Shantsila, E., & Lip, G. Y. H. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-55429-9.00004-2
Self-citationNielsen, P. B., Buchan, I. E., & Lip, G. Y. H. (2019) · The American Journal of Medicine · doi:10.1016/j.amjmed.2019.01.038
Self-citationSchlaganfall – Prävalenz, Bedeutung und Implikationen für die Prävention und Gesundheitsförderung
Uphaus, T., & Gröschel, K. (2021) · Springer Reference Pflege, Therapie, Gesundheit · doi:10.1007/978-3-662-62426-5_43
Capiau, A., Grymonprez, M., Backer, T. L. M. D., Gevaert, S., Boussery, K., & Lahousse, L. (2021) · Tijdschrift voor Geneeskunde · doi:10.47671/tvg.77.21.107
- Authors
- Skjøth, F., Nielsen, P., Larsen, T. B., & Lip, G.
- Affiliations
- Birmingham City Hospital (GB)
- Aalborg University Hospital (DK)
- Corresponding author
- Lip, Gregory
- Venue
- Thrombosis and Haemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2015
- Volume
- 114
- Issue
- 10
- Pages
- 826-834
- ISSN
- 0340-6245 (ISSN-L)
- 2567-689X
- OpenAlex
- W2160740406
- Cited by
- 106
- References
- 30
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 15 · 2016: 39 · 2015: 4
- FWCI
- 16.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- 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, CHA2DS2-VASc score, oral anticoagulation, warfarin, aspirin, stroke prevention, intracranial hemorrhage, bleeding risk, net clinical benefit
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Aspirin, Atrial Fibrillation, Decision Support Techniques, Denmark, Female, Fibrinolytic Agents, Hemorrhage, Humans, Male, Middle Aged, Predictive Value of Tests, Registries, Risk Factors, Time Factors, Warfarin, Treatment Outcome, Risk Assessment, Patient Selection, Stroke
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