Anticoagulation Timing in Acute Stroke With Atrial Fibrillation According to Chronic Kidney Disease: The OPTIMAS Trial
- PMID: 40402086
- DOI: 10.1161/STROKEAHA.125.051457
Anticoagulation Timing in Acute Stroke With Atrial Fibrillation According to Chronic Kidney Disease: The OPTIMAS Trial
Abstract
Background: Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of clinical relevance.
Methods: OPTIMAS (Optimal Timing of Anticoagulation After Acute Ischemic Stroke With Atrial Fibrillation) was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7-14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality.
Results: We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67-1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36-2.25]; Pinteraction=0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD (Pinteraction values of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively).
Conclusions: Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.
Keywords: atrial fibrillation; brain ischemia; cerebral hemorrhage; ischemic stroke; renal insufficiency, chronic.
Conflict of interest statement
Dr Werring reports consulting fees from Novo Nordisk, the National Institute for Health and Clinical Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility Trial: Randomised, Placebo Controlled, Double-Blind Crossover Study of Effects of Sildenafil on Cerebral Arterial Pulsatility in Patients With Cryptogenic or Lacunar Stroke and Small Vessel Disease); participation as the Steering Committee Chair for the MACE-ICH (Mannitol for Cerebral Oedema After Intracerebral Haemorrhage) and PLINTH (Platform Study for Intracerebral Haemorrhage) trials; serving as the President of the British and Irish Association of Stroke Physicians; and holding a National Institute for Health and Care Research Senior Investigator Award. B. Norrving reports payments for work in a data safety monitoring board in the HOVID trial (Hypertension, Oxidative Stress, and Vascular Damage in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) and fees from Simbec Orion. M. James reports travel or speaker honoraria from Daiichi Sankyo, Portola, and Boehringer Ingelheim. Dr Cohen reports speaker honoraria from Technoclone (paid to UCL Hospitals Charity) and GSK; consulting fees from UCB Biopharma (paid to UCL Hospitals Charity); and advisory board fees from Roche and Argenx. Dr Lip reports being a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthos (no fees received personally) and is a National Institute for Health and Care Research Senior Investigator. Dr Hunter reports grants from the National Institute for Health and Care Research for the Dementia Policy Research Unit-Queen Mary and the Research Support Service and being the Co-Chair of the EU Transforming Health and Care Systems Funding Board in 2023. Dr Ford reports receiving consulting fees from AstraZeneca for a project on management of stroke due to intracerebral hemorrhage (payment to his employer) and Bayer (for lecture on models of the National Health Service industry working) and is the Chief Executive of Health Innovation (Oxford and Thames Valley), which has multiple joint working agreements and medical education grants with industry partners that have contracts with Oxford University Hospitals NHS Trust. N. Sprigg reports grants from the National Institute for Health Research. Dr Freemantle reports consulting fees received from ALK, Sanofi Aventis, Gedeon Richter, Abbot, Galderma, AstraZeneca, Ipsen, Vertex, Thea, Novo Nordisk, Aimmune, and Gilead. Dr Wheeler reports compensation from Sana Therapeutics, Vertex Pharmaceuticals, and Silence Pharmaceuticals for data and safety monitoring services; grants from ProKidney, Amgen, Zydus Pharmaceuticals (USA), Inc, Reata, Merck Sharp, Dohme, Boehringer Ingelheim, Bayer, Galderma, GlaxoSmithKline, Astellas Pharma, Janssen Biotech, Napp, Vifor Fresenius, Mundipharma, and Tricida; and compensation from AstraZeneca, Galderma, and Fondazione Internazionale Menarini for consultant services. The other authors report no conflicts.
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