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How do anticoagulated atrial fibrillation patients who suffer ischemic stroke or spontaneous intracerebral hemorrhage differ?

ABSTRACT: BACKGROUND:Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC-treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR). HYPOTHESIS:We assumed that in AF patients suffering ischemic stroke/TIA or ICH, patient characteristics could be different in patients with therapeutic INR than in patients with warfarin. METHODS:FibStroke is a multicenter, retrospective registry collating details of AF patients with ischemic stroke/TIA or intracranial hemorrhage in 2003-2012. This substudy included AF patients on OAC with first lifetime ischemic stroke/TIA or spontaneous ICH. RESULTS:A total of 1457 patients with 1290 ischemic strokes/TIAs and 167 ICHs were identified. Of these, 553 (42.9%) strokes/TIAs and 96 (57.5%) ICHs occurred in patients with INR within therapeutic range. During OAC with therapeutic INR, congestive heart failure (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.18-4.58) and hypercholesterolemia (OR: 2.52, 95% CI: 1.51-4.19) were more common in patients with ischemic stroke/TIA, whereas a history of bleeding (OR: 0.30, 95% CI: 0.11-0.82) was less common when compared with patients with ICH. In the whole cohort, renal impairment (OR: 1.86, 95% CI: 1.23-2.80) and mechanical valve prosthesis (OR: 4.41, 95% CI: 1.32-14.7) were overrepresented in patients with stroke/TIA, whereas aspirin use (OR: 0.52, 95% CI: 0.30-0.91) and high INR (OR: 0.40, 95% CI: 0.33-0.48) were overrepresented in patients with ICH. CONCLUSIONS:In anticoagulated AF patients with therapeutic INR and first lifetime cerebrovascular event, congestive heart failure and hypercholesterolemia were associated with ischemic stroke/TIA and history of bleeding with ICH.

SUBMITTER: Lehtola H

PROVIDER: S-EPMC6490034 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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How do anticoagulated atrial fibrillation patients who suffer ischemic stroke or spontaneous intracerebral hemorrhage differ?

Lehtola Heidi H Hartikainen Juha J Hartikainen Päivi P Kiviniemi Tuomas T Nuotio Ilpo I Palomäki Antti A Ylitalo Antti A Airaksinen K E Juhani KEJ Mustonen Pirjo P

Clinical cardiology 20180510 5

<h4>Background</h4>Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC-treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR).<h4>Hypothesis</h4>We assumed that in AF patients suffering ischemic stroke/TIA ...[more]

PMID: 29745996

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Project description:Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross-sectional study was done on consecutive oral anticoagulant-treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel-Oral-Anticoagulants-In-Stroke-Patients)-Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32-0.82], 0.48 [0.26-0.86], 0.55 [0.34-0.89], and 0.82 [0.75-0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87-14.04], 1.37 [1.04-1.81] per 10 years, 1.19 [1.10-1.29] per 10 mm Hg, and 1.81 [1.09-3.03]). Cerebral microbleeds and moderate-to-severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34-6.18], and 2.62 [1.28-5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31-0.90], 0.29 [0.05-0.97], 0.48 [0.30-0.76], and 0.32 [0.13-0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02353585.

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.

Project description:Background and purposeAnticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH).MethodsWe conducted a retrospective study using the California State Inpatient Database including all nonfederal hospital admissions in California from 2005 to 2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke before or at the time of ECH diagnosis. We calculated adjusted hazard ratios for ischemic stroke during follow-up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and comorbidities. In subgroup analyses, subjects were stratified by primary ECH diagnosis, severity/type of ECH, age, CHA2DS2-VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer.ResultsWe identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years.ConclusionsPatients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.

Project description:Spontaneous Intracerebral hemorrhage (ICH) is a devastating injury that accounts for 10-15% of all strokes. The rupture of cerebral blood vessels damaged by hypertension or cerebral amyloid angiopathy creates a space-occupying hematoma that contributes toward neurological deterioration and high patient morbidity and mortality. Numerous protocols have explored a role for surgical decompression of ICH via craniotomy, stereotactic guided endoscopy, and minimally invasive catheter/tube evacuation. Studies including, but not limited to, STICH, STICH-II, MISTIE, MISTIE-II, MISTIE-III, ENRICH, and ICES have all shown that, in certain limited patient populations, evacuation can be done safely and mortality can be decreased, but functional outcomes remain statistically no different compared to medical management alone. Only 10-15% of patients with ICH are surgical candidates based on clot location, medical comorbidities, and limitations regarding early surgical intervention. To date, no clearly effective treatment options are available to improve ICH outcomes, leaving medical and supportive management as the standard of care. We recently identified that remote ischemic conditioning (RIC), the non-invasive, repetitive inflation-deflation of a blood pressure cuff on a limb, non-invasively enhanced hematoma resolution and improved neurological outcomes via anti-inflammatory macrophage polarization in pre-clinical ICH models. Herein, we propose a pilot, placebo-controlled, open-label, randomized trial to test the hypothesis that RIC accelerates hematoma resorption and improves outcomes in ICH patients. Twenty ICH patients will be randomized to receive either mock conditioning or unilateral arm RIC (4 cycles × 5 min inflation/5 min deflation per cycle) beginning within 48 h of stroke onset and continuing twice daily for one week. All patients will receive standard medical care according to latest guidelines. The primary outcome will be the safety evaluation of unilateral RIC in ICH patients. Secondary outcomes will include hematoma volume/clot resorption rate and functional outcomes, as assessed by the modified Rankin Scale (mRS) at 1- and 3-months post-ICH. Additionally, blood will be collected for exploratory genomic analysis. This study will establish the feasibility and safety of RIC in acute ICH patients, providing a foundation for a larger, multi-center clinical trial.

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How do anticoagulated atrial fibrillation patients who suffer ischemic stroke or spontaneous intracerebral hemorrhage differ?

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How do anticoagulated atrial fibrillation patients who suffer ischemic stroke or spontaneous intracerebral hemorrhage differ?

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