Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review

The optimal timing for initiating direct oral anticoagulants (DOACs) for secondary stroke prevention in patients with atrial fibrillation and acute ischaemic stroke remains controversial due to concerns about haemorrhagic transformation. This study aimed to analyse the efficacy and safety of early v...

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Main Authors: Bengt Herweg, Aravind Dilli Babu, Sahib Singh, Asher Gorantla, Mirza Faris Ali Baig, Ram Bhutani, Harika Davuluri, Lekshminarayan Raghavakurup
Format: Article
Language:English
Published: BMJ Publishing Group 2024-11-01
Series:Open Heart
Online Access:https://openheart.bmj.com/content/11/2/e003002.full
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author Bengt Herweg
Aravind Dilli Babu
Sahib Singh
Asher Gorantla
Mirza Faris Ali Baig
Ram Bhutani
Harika Davuluri
Lekshminarayan Raghavakurup
author_facet Bengt Herweg
Aravind Dilli Babu
Sahib Singh
Asher Gorantla
Mirza Faris Ali Baig
Ram Bhutani
Harika Davuluri
Lekshminarayan Raghavakurup
author_sort Bengt Herweg
collection DOAJ
description The optimal timing for initiating direct oral anticoagulants (DOACs) for secondary stroke prevention in patients with atrial fibrillation and acute ischaemic stroke remains controversial due to concerns about haemorrhagic transformation. This study aimed to analyse the efficacy and safety of early versus late DOAC initiation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted, searching major databases (PubMed, Embase, Cochrane Library and ClinicalTrials.gov) up to May 2024. A total of 11 studies were identified, comprising nine cohort studies (75.5% weight) and two randomised controlled trials (RCTs) (24.5% weight), involving 13 020 participants. The early DOAC group (mean initiation 3.5±1.29 days) included 6250 participants, while the late group (5.7±1.25 days) had 6770 participants. Outcome measures included recurrent ischaemic stroke (RIS), intracranial haemorrhage (ICH), systemic embolism, major haemorrhage (MH), non-major haemorrhage (NMH) and all-cause mortality. Statistical analysis using the Cochrane Review Manager calculated ORs and 95% CIs via the Mantel-Haenszel random effects model. This pooled meta-analysis revealed that the early DOAC group had lower rates of RIS (2.2% vs 2.9%, OR 0.72, 95% CI 0.52 to 0.98, p=0.04, I2=40%) and ICH (0.51% vs 0.93%, OR 0.45, 95% CI 0.29 to 0.70, p<0.05, I2=0%) compared with the late DOAC group. Subgroup analysis of RCTs and cohort studies showed reduced RIS and ICH risks in the early DOAC group, with moderate heterogeneity. In the sensitivity analysis, the early group (<4 days) had a lower risk of RIS compared with the late group (>4 days) without a statistically significant impact on ICH. No significant differences in MH, NMH, systemic embolism or all-cause mortality were observed between either group; however, a limited number of RCTs and moderate heterogeneity weakened the conclusions. Additional RCTs are needed to provide more definitive insights.
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spelling doaj-art-e8018c25bcde4bd3a3692acaf08c9c502024-12-13T11:40:13ZengBMJ Publishing GroupOpen Heart2053-36242024-11-0111210.1136/openhrt-2024-003002Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic reviewBengt Herweg0Aravind Dilli Babu1Sahib Singh2Asher Gorantla3Mirza Faris Ali Baig4Ram Bhutani5Harika Davuluri6Lekshminarayan Raghavakurup7Electrophysiology, University of South Florida, Tampa, Florida, USAInternal Medicine, Sinai Hospital (LifeBridge Health), Baltimore, Maryland, USAInternal Medicine, Sinai Hospital (LifeBridge Health), Baltimore, Maryland, USACardiology, SUNY Downstate Medical Center, New York City, New York, USAInternal Medicine, Asante Three Rivers Medical Center, Grants Pass, Oregon, USAInternal Medicine, Sinai Hospital (LifeBridge Health), Baltimore, Maryland, USAInternal Medicine, Sinai Hospital (LifeBridge Health), Baltimore, Maryland, USAInternal Medicine, Sinai Hospital (LifeBridge Health), Baltimore, Maryland, USAThe optimal timing for initiating direct oral anticoagulants (DOACs) for secondary stroke prevention in patients with atrial fibrillation and acute ischaemic stroke remains controversial due to concerns about haemorrhagic transformation. This study aimed to analyse the efficacy and safety of early versus late DOAC initiation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted, searching major databases (PubMed, Embase, Cochrane Library and ClinicalTrials.gov) up to May 2024. A total of 11 studies were identified, comprising nine cohort studies (75.5% weight) and two randomised controlled trials (RCTs) (24.5% weight), involving 13 020 participants. The early DOAC group (mean initiation 3.5±1.29 days) included 6250 participants, while the late group (5.7±1.25 days) had 6770 participants. Outcome measures included recurrent ischaemic stroke (RIS), intracranial haemorrhage (ICH), systemic embolism, major haemorrhage (MH), non-major haemorrhage (NMH) and all-cause mortality. Statistical analysis using the Cochrane Review Manager calculated ORs and 95% CIs via the Mantel-Haenszel random effects model. This pooled meta-analysis revealed that the early DOAC group had lower rates of RIS (2.2% vs 2.9%, OR 0.72, 95% CI 0.52 to 0.98, p=0.04, I2=40%) and ICH (0.51% vs 0.93%, OR 0.45, 95% CI 0.29 to 0.70, p<0.05, I2=0%) compared with the late DOAC group. Subgroup analysis of RCTs and cohort studies showed reduced RIS and ICH risks in the early DOAC group, with moderate heterogeneity. In the sensitivity analysis, the early group (<4 days) had a lower risk of RIS compared with the late group (>4 days) without a statistically significant impact on ICH. No significant differences in MH, NMH, systemic embolism or all-cause mortality were observed between either group; however, a limited number of RCTs and moderate heterogeneity weakened the conclusions. Additional RCTs are needed to provide more definitive insights.https://openheart.bmj.com/content/11/2/e003002.full
spellingShingle Bengt Herweg
Aravind Dilli Babu
Sahib Singh
Asher Gorantla
Mirza Faris Ali Baig
Ram Bhutani
Harika Davuluri
Lekshminarayan Raghavakurup
Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review
Open Heart
title Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review
title_full Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review
title_fullStr Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review
title_full_unstemmed Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review
title_short Optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation: a comprehensive meta-analysis and systematic review
title_sort optimal timing of oral anticoagulation initiation in patients with acute ischaemic stroke and atrial fibrillation a comprehensive meta analysis and systematic review
url https://openheart.bmj.com/content/11/2/e003002.full
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