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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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“VKA therapy is superior single or DAPT therapy with respect to stroke risk reduction.(18,19) However, the patient‐level efficacy of VKA is dependent on time spent within the therapeutic range (TTR), defined as an internal normalized ratio (INR) between 2.”
BackgroundAtrial Fibrillation Begets Myocardial Infarction
Dukes, J. W., & Marcus, G. M. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.11392 · Cited by 16
Wyse, D. G. (2007) · Circulation · doi:10.1161/circulationaha.107.704122 · Cited by 16
Kim, W., Park, J., Kang, K., Cho, Y., Hong, K., Lee, S. J., Ko, Y., Lee, K. B., Park, T. H., Lee, J., et al. (2016) · Journal of Clinical Neurology · doi:10.3988/jcn.2016.12.1.34 · Cited by 15
Assessment and management of coagulopathy in neurocritical care
Salem, A. M., Roh, D. J., Kitagawa, R. S., Choi, H. A., & Chang, T. R. (2019) · Journal of Neurocritical Care · doi:10.18700/jnc.190086 · Cited by 15
Caracciolo, A., Mazzone, P., Laterra, G., Garcia-Ruiz, V., Polimeni, A., Galasso, S., Saporito, F., Carerj, S., D’Ascenzo, F., Marquis‐Gravel, G., et al. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8112016 · Cited by 15
Chan, B., Wong, L. Y. H., Tan, B. Y., Yeo, L. L. L., & Venketasubramanian, N. (2024) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd11020048 · Cited by 19
“In the ACTIVE-W trial (2003–2005), patients who were warfarin candidates were randomized between ASA+CLO and warfarin, and the study was stopped early due to the clear superiority of warfarin [10].”
MethodFauchier, L., Pellegrin, C., Bernard, A., Clémenty, N., Angoulvant, D., Lip, G. Y. H., & Babuty, D. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.02.042 · Cited by 15
Su, Y., Cheng, X., & Dong, Q. (2015) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12419 · Cited by 15
“The occurrence of major and severe hemorrhage was similar between DAPT and warfarin groups [37].”
ResultRodríguez‐Mañero, M., Bertomeu‐González, V., Cordero, A., Arribas, J. M., Mazón, P., Fácila, L., Cosín, J., Galve, E., Lekuona, I., González‐Juanatey, J. R., et al. (2013) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2012.06.011 · Cited by 15
“Studies published in the last decade have shown that both aspirin monotherapy and dual antiplatelet therapy with clopidogrel are less effective than OAC and furthermore are associated with higher rates of bleeding.(17,18) It is therefore encouraging that the awareness of physicians (both general practitioners and card…”
ResultManagement of Atrial Fibrillation in Elderly Adults
Desai, Y. B., El‐Chami, M. F., León, A. R., & Merchant, F. M. (2016) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14483 · Cited by 16
“antiplatelet therapy with warfarin, bleeding rates were comparable between the two arms, but ischemic stroke reduction was significantly better with warfarin, leading to early termination of the trial.(31) Although few studies have compared DOACs with antiplatelet therapy, the Apixaban Versus Acetylsalicylic Acid to P…”
ResultManagement of Intracranial Hemorrhage in the Anticoagulated Patient
Macdonald, R. L. (2018) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2018.06.013 · Cited by 16
Angelini, F., Fortuni, F., Tsivgoulis, G. K., Agnelli, G., Bocchino, P. P., Franchin, L., FILIPPO, O. D., Bellettini, M., D’Ascenzo, F., Crimi, G., et al. (2020) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-020-07068-9 · Cited by 15
Furusho, H., Takamura, M., Takata, S., Sakagami, S., Hirazawa, M., Kato, T., Murai, H., Okajima, M., & Kaneko, S. (2008) · Circulation Journal · doi:10.1253/circj.cj-08-0290 · Cited by 15
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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