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Early Anticoagulation in Patients with Acute Ischemic Stroke Due to Atrial Fibrillation: A Systematic Review and Meta-Analysis.

ABSTRACT: Introduction: There is uncertainty regarding the optimal timing for initiation of oral anticoagulation in patients with acute ischemic stroke (AIS) due to atrial fibrillation (AF). Methods: We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and prospective observational studies to assess the efficacy and safety of early anticoagulation in AF-related AIS (within 1 week versus 2 weeks). A second comparison was performed assessing the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin-K antagonists (VKAs) in the two early time windows. The outcomes of interest were IS recurrence, all-cause mortality, symptomatic intracerebral haemorrhage (sICH) and any ICH. Results: Eight eligible studies (6 observational, 2 RCTs) were identified, including 5616 patients with AF-related AIS who received early anticoagulation. Patients that received anticoagulants within the first week after index stroke had similar rate of recurrent IS, sICH and all-cause mortality compared to patients that received anticoagulation within two weeks (test for subgroup differences p = 0.1677; p = 0.8941; and p = 0.7786, respectively). When DOACs were compared to VKAs, there was a significant decline of IS recurrence in DOAC-treated patients compared to VKAs (RR: 0.65; 95%CI: 0.52-0.82), which was evident in both time windows of treatment initiation. DOACs were also associated with lower likelihood of sICH and all-cause mortality. Conclusions: Early initiation of anticoagulation within the first week may have a similar efficacy and safety profile compared to later anticoagulation (within two weeks), while DOACs seem more effective in terms of IS recurrence and survival compared to VKAs.

SUBMITTER: Palaiodimou L

PROVIDER: S-EPMC9457225 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Early Anticoagulation in Patients with Acute Ischemic Stroke Due to Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Palaiodimou Lina L Stefanou Maria-Ioanna MI Katsanos Aristeidis H AH Paciaroni Maurizio M Sacco Simona S De Marchis Gian Marco GM Shoamanesh Ashkan A Malhotra Konark K de Sousa Diana Aguiar DA Lambadiari Vaia V Kantzanou Maria M Vassilopoulou Sofia S Toutouzas Konstantinos K Filippou Dimitrios K DK Seiffge David J DJ Tsivgoulis Georgios G

Journal of clinical medicine 20220825 17

<b>Introduction:</b> There is uncertainty regarding the optimal timing for initiation of oral anticoagulation in patients with acute ischemic stroke (AIS) due to atrial fibrillation (AF). <b>Methods:</b> We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and prospective observational studies to assess the efficacy and safety of early anticoagulation in AF-related AIS (within 1 week versus 2 weeks). A second comparison was performed assessing the ef ...[more]

PMID: 36078915

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Project description:ObjectiveThe aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes.MethodsThis was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months.ResultsOf 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51).InterpretationPrior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Project description:BackgroundNon-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved.AimsWe sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF).MethodsWe recruited hospitalised patients (2013-2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence.ResultsAmong 396 patients (median age 75.0 years, interquartile range [IQR] 70-80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12-33]; median ARMS score 17 [IQR 17-19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence.ConclusionsAdherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.KEY MESSAGESAdherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.Independent patient-related factors rather than composite scores were associated with poor adherence.The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.

Project description:Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe. Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation. Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0-3 for transient ischemic attack (TIA), 3-5 for small-sized AIS (<1.5 cm), and 7-9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded. Study Outcomes: Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities]. Sample Size Estimates: Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A). Discussion: AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02283294.

Project description:To understand anticoagulation therapy in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) after receiving reperfusion treatments in the real world. This retrospective study collected basic clinical data, the initiation time of anticoagulation therapy, treatment plans, and prognosis of AIS patients with AF who underwent intravenous thrombolysis (IVT), and/or endovascular thrombectomy (EVT) from January 2019 to January 2022 in four tertiary hospitals in Jiangxi Province. A multivariate logistic regression analysis was used to analyze the factors influencing anticoagulation therapy in these patients. The reasons for delay or non-initiation of anticoagulation therapy were analyzed by questionnaire. A total of 410 patients met the selection criteria, including 168 (41.0%) in the IVT group, 144 (35.1%) in the EVT group, and 98 (23.9%) in the IVT + EVT group. Initiation of anticoagulation therapy within 14 days post-AIS was found in 175 patients in total (42.7%), which is significantly different in three groups (49.7% in IVT group, 30.3% in EVT group, and 20.0% in IVT + EVT groups, P < 0.01). Multivariate logistic regression analysis revealed that prior use of antiplatelet drugs was more common in patients receiving early anticoagulation therapy (OR = 0.122, 95% CI 0.065-0.228, P < 0.01). Patients receiving no anticoagulation had higher-3-days post-reperfusion NIHSS score (OR = 1.109, 95% CI 1.073-1.147, P < 0.01) and more in-hospital haemorrhagic transformation (OR = 2.572, 95% CI 1.423-4.648, P < 0.01). Of all patients, 281 had a favorable 90-day prognosis (mRS score 0-2), including 152 (86.9%) in the early anticoagulation group and 129 (54.9%) in the delay anticoagulation group (P < 0.01). Postoperative 90-day outcomes included 25 (6.1%) cases of recurrent ischemic stroke (P = 0.55) and 27 (6.6%) bleeding events (P = 0.32). Early initiation of anticoagulation therapy improves 90-day outcomes in NVAF post-related AIS patients with related AF after receiving reperfusion treatments; however, the initiation of anticoagulation in most patients might be much later than the currently recommended timing in real world.

Project description:Background and Purpose- Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (AF) are at risk for ischemic events. While risk calculators (CHA2DS2-VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and major bleeding in AF patients, decisions about anticoagulation must consider the net clinical benefit of anticoagulation. Furthermore, stroke and bleeding risk are highly correlated, making decisions more difficult. Methods- We examined patients in the GERFHS III study (Genetic and Environmental Risk Factors for Hemorrhagic Stroke)-a population-based retrospective study of spontaneous ICH patients without a structural or traumatic cause in the Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. CHA2DS2-VASc and HAS-B(L)ED (minus L because labile international normalized ratio was unavailable) scores were calculated for ICH patients with AF. Using a Markov state transition model, we estimated net clinical benefit of anticoagulation relative to no treatment in quality-adjusted life years (QALYs). We defined minimal clinically relevant benefit as 0.1 QALYs. Results- Among 1186 cases of spontaneous ICH, 95 cases had AF and met our survival criteria. Within 1 year, 8 of 95 (8%) would be expected to have a major bleeding event on anticoagulation, and 5 of 95 (5%) of patients would be expected to have an ischemic stroke off anticoagulation. Sixty-eight of 95 (71%) patients would have higher risk for major bleeding than for ischemic stroke. Anticoagulation with directly acting anticoagulants would result in no clinically significant gain or loss in 73%. Roughly 12% would gain >0.1 QALYs, and 15% would lose >0.1 QALYs. Among patients receiving aspirin, most have no significant net clinical benefit or loss. Overall, anticoagulation of the entire cohort would result in an aggregate loss of 0.92 QALYs. Conclusions- Our analysis suggests that universal anticoagulation after ICH would be associated with a net loss of QALY. Additional factors should be considered before anticoagulating patients with AF after ICH. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00930280.

Dataset Information

Early Anticoagulation in Patients with Acute Ischemic Stroke Due to Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Publications

Early Anticoagulation in Patients with Acute Ischemic Stroke Due to Atrial Fibrillation: A Systematic Review and Meta-Analysis.

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