Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF
Abstract
Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA).Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767.Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08).Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF.Funding Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.
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Long-term oral anticoagulation with a VKA or NOAC conveys benefits in AF patients who survived a stroke.
“Long-term OAC with a VKA 363,[479][480][481] or NOAC 482 conveys benefits in AF patients who survived a stroke.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [480]
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- Authors
- Hankey, G. J., Patel, M. R., Stevens, S. R., Becker, R. C., Breithardt, G., Carolei, A., Diener, H.-C., Donnan, G. A., Halperin, J. L., Mahaffey, K. W., Mas, J.-L., Massaro, A., Norrving, B., Nessel, C. C., Paolini, J. F., Roine, R. O., Singer, D. E., Wong, L., Califf, R. M., Fox, K. A., & Hacke, W.
- Affiliations
- Royal Perth Hospital (AU)
- Duke Medical Center (US)
- University of Münster (DE)
- University of L'Aquila (IT)
- Essen University Hospital (DE)
- The University of Melbourne (AU)
- Icahn School of Medicine at Mount Sinai (US)
- Centre Hospitalier Sainte-Anne (FR)
- Universidade de São Paulo (BR)
- Lund University (SE)
- Janssen Research & Development (United States) (US)
- Turku University Hospital (FI)
- Harvard University (US)
- Duke University (US)
- Edinburgh Royal Infirmary (GB)
- Heidelberg University (DE)
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 11
- Issue
- 4
- Pages
- 315-322
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2110258159
- Cited by
- 354
- References
- 16
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 17 · 2022: 16 · 2021: 20 · 2020: 19 · 2019: 24 · 2018: 24 · 2017: 23 · 2016: 39 · 2015: 32 · 2014: 45 · 2013: 44 · 2012: 24
- FWCI
- 29.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Funders
- GlaxoSmithKline
- Medicines Company
- Johnson and Johnson
- Daiichi-Sankyo
- Merck
- Novartis
- Bayer
- Momenta Pharmaceuticals
- Eli Lilly and Company
- AstraZeneca
- Bristol-Myers Squibb
- Boehringer Ingelheim
- 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
- rivaroxaban, warfarin, atrial fibrillation, stroke history, transient ischemic attack, stroke prevention, systemic embolism, bleeding risk, subgroup analysis, ROCKET AF, direct oral anticoagulants, non-inferiority, anticoagulant safety, international normalized ratio, oral anticoagulation
- MeSH terms
- Rivaroxaban, Aged, Anticoagulants, Atrial Fibrillation, Ischemic Attack, Transient, Double-Blind Method, Humans, Morpholines, Thiophenes, Warfarin, Multicenter Studies as Topic, Treatment Outcome, Stroke, Secondary Prevention, Intention to Treat Analysis
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