Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) : Protocol for a randomized controlled trial
(2022) In International Journal of Stroke 17(5). p.583-589- Abstract
Rationale: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four... (More)
Rationale: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design: OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes: The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target: A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion: OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938
(Less)
- author
- author collaboration
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- acute ischemic stroke, anticoagulation, Atrial fibrillation, DOAC, timing
- in
- International Journal of Stroke
- volume
- 17
- issue
- 5
- pages
- 583 - 589
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85122942607
- pmid:35018878
- ISSN
- 1747-4930
- DOI
- 10.1177/17474930211057722
- language
- English
- LU publication?
- yes
- id
- f2bca6f0-7530-48c2-b76a-7185192dd5d1
- date added to LUP
- 2022-02-24 15:30:04
- date last changed
- 2024-04-20 15:42:17
@article{f2bca6f0-7530-48c2-b76a-7185192dd5d1,
abstract = {{<p>Rationale: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design: OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes: The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target: A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion: OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938</p>}},
author = {{Best, Jonathan G. and Arram, Liz and Ahmed, Norin and Balogun, Maryam and Bennett, Kate and Bordea, Ekaterina and Campos, Marta G. and Caverly, Emilia and Chau, Marisa and Cohen, Hannah and Dehbi, Hakim Moulay and Doré, Caroline J. and Engelter, Stefan T. and Fenner, Robert and Freemantle, Nick and Hunter, Rachael and James, Martin and Lip, Gregory Y.H. and Murray, Macey L. and Norrving, Bo and Sprigg, Nikola and Veltkamp, Roland and Zaczyk, Iwona and Werring, David J.}},
issn = {{1747-4930}},
keywords = {{acute ischemic stroke; anticoagulation; Atrial fibrillation; DOAC; timing}},
language = {{eng}},
number = {{5}},
pages = {{583--589}},
publisher = {{Wiley-Blackwell}},
series = {{International Journal of Stroke}},
title = {{Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) : Protocol for a randomized controlled trial}},
url = {{http://dx.doi.org/10.1177/17474930211057722}},
doi = {{10.1177/17474930211057722}},
volume = {{17}},
year = {{2022}},
}