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Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial
Abstract
Background Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.Methods Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.Results The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).Conclusion Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.
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“VKA therapy prevents stroke, non-central nervous system embolus, myocardial infarction, and vascular death better than single or dual antiplatelet therapy with aspirin and clopidogrel (annual risk of 5.6% for aspirin and clopidogrel vs. 3.9% with VKA therapy).431”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [431]
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Gwyn, J. C., Thomas, M. R., & Kirchhof, P. F. (2017) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvx002 · Cited by 21
Combining Antiplatelet and Antithrombotic Therapy (Triple Therapy): What Are the Risks and Benefits?
Asencio, L. A., Huang, J. J., & Alpert, J. S. (2014) · The American Journal of Medicine · doi:10.1016/j.amjmed.2014.02.030 · Cited by 21
Non-vitamin K oral anticoagulants in atrial fibrillation: Where are we now?
Dzeshka, M. S., & Lip, G. Y. H. (2014) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2014.10.017 · Cited by 21
“[18] ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al.”
MethodWeimar, C., Benemann, J., Katsarava, Z., Weber, R., & Diener, H. (2008) · European Neurology · doi:10.1159/000144085 · Cited by 21
Wu, B. Y., Li, K., Liu, X., & He, B. (2013) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-013-6490-9 · Cited by 21
Manjila, S. V., Masri, T. J., Shams, T., Chowdhry, S. A., Sila, C., & Selman, W. R. (2011) · Neurosurgical FOCUS · doi:10.3171/2011.2.focus1164 · Cited by 19
Clopidogrel “resistance”: Pre- vs post-receptor determinants
Hurst, N. L., Nooney, V. B., Raman, B., Chirkov, Y. Y., Caterina, R. D., & Horowitz, J. D. (2013) · Vascular Pharmacology · doi:10.1016/j.vph.2013.10.002 · Cited by 21
“Furthermore, althoughclopidogrel and aspirin in combination have been utilized to prevent thromboembolic events in patientswith atrialfibrillation, they are less effective than anticoagulation with warfarin [5].”
BackgroundPersson, J., Lindbäck, J., Hofman‐Bang, C., Lagerqvist, B., Stenestrand, U., & Samnegård, A. (2011) · EuroIntervention · doi:10.4244/eijv6i9a183 · Cited by 21
Resuming anticoagulant therapy after intracerebral bleeding
Becattini, C., Sembolini, A., & Paciaroni, M. (2016) · Vascular Pharmacology · doi:10.1016/j.vph.2016.05.012 · Cited by 22
Stroke Prevention in Atrial Fibrillation
Mtwesi, V., & Amit, G. (2019) · Medical Clinics of North America · doi:10.1016/j.mcna.2019.05.006 · Cited by 21
JACKSON, K. P., Gersh, B. J., Stockbridge, N., Fleming, T. R., Temple, R., Califf, R. M., Connolly, S. J., Wallentin, L. C., & Granger, C. B. (2008) · American Heart Journal · doi:10.1016/j.ahj.2008.01.023 · Cited by 21
Coronary Stents and Chronic Anticoagulation
Sourgounis, A., Lipiecki, J., Lo, T., & Hamon, M. (2009) · Circulation · doi:10.1161/circulationaha.108.834861 · Cited by 21
Fiedler, K. A., Byrne, R. A., Schulz, S., Sibbing, D., Mehilli, J., Ibrahim, T., Mæng, M., Laugwitz, K., Kastrati, A., & Sarafoff, N. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.01.005 · Cited by 22
“Previous studies have shown that both DAT and VKA are each associated with an annual risk of total bleeding events of up to 13% to 15% per year.(10) Moreover, because each regimen impairs hemostasis by distinct mechanistic pathways, there is concern that adding VKA to DAT results in an additive risk of clinically impo…”
Antithrombotic Medication for Cardioembolic Stroke Prevention
Font, M. À., Krupiński, J., & Arboix, A. (2011) · Stroke Research and Treatment · doi:10.4061/2011/607852 · Cited by 22
Bontempo, L. J., & Goralnick, E. (2011) · Emergency Medicine Clinics of North America · doi:10.1016/j.emc.2011.08.008 · Cited by 20
Atrial fibrillation, stroke, and quality of life
Chinitz, J. S., Castellano, J. M., Kovacic, J. C., & Fuster, V. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06494.x · Cited by 20
Cangemi, R., Pignatelli, P., Carnevale, R., Corazza, G. R., Pastori, D., Farcomeni, A., Basili, S., Davı̀, G., Ferro, D., Hiatt, W. R., et al. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.04.142 · Cited by 20
“time [32,33].”
Can We Predict Outcomes in Atrial Fibrillation?
Desai, N. R., & Giugliano, R. P. (2012) · Clinical Cardiology · doi:10.1002/clc.20989 · Cited by 20
Update on the management of atrial fibrillation
Amerena, J. V., Walters, T. E., Mirzaee, S., & Kalman, J. M. (2013) · The Medical Journal of Australia · doi:10.5694/mja13.10191 · Cited by 20
Metadata
- Authors
- ‡
- Corresponding author
- ‡
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 367
- Issue
- 9526
- Pages
- 1903-1912
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2159193915
- Cited by
- 1,952
- References
- 24
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 33 · 2023: 44 · 2022: 44 · 2021: 68 · 2020: 68 · 2019: 82 · 2018: 92 · 2017: 87 · 2016: 107 · 2015: 118 · 2014: 134 · 2013: 155 · 2012: 208
- FWCI
- 77.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Sanofi
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Keywords
- atrial fibrillation, clopidogrel, aspirin, oral anticoagulation, stroke prevention, vascular events, major bleeding, anticoagulation monitoring, clopidogrel resistance, irbesartan, antiplatelet therapy, vascular death, myocardial infarction
- MeSH terms
- Clopidogrel, Irbesartan, Aged, Anticoagulants, Aspirin, Atrial Fibrillation, Biphenyl Compounds, Drug Therapy, Combination, Humans, Platelet Aggregation Inhibitors, Risk Factors, Severity of Illness Index, Tetrazoles, Ticlopidine, International Normalized Ratio, Stroke
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