Cost-effectiveness of CYP2C19 genotyping to guide antiplatelet therapy for acute minor stroke and high-risk transient ischemic attack.
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ABSTRACT:
SUBMITTER: Cai Z
PROVIDER: S-EPMC8016871 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA.
| S-EPMC4901037 | biostudies-other
Project description:Studies on antiplatelet effect of ticagrelor/aspirin and clopidogrel/aspirin in patients with acute minor stroke and transient ischemic attack (TIA) stratified by CYP2C19 metabolizer status is limited. We gained data from the Platelet Reactivity In Non-disabling Cerebrovascular Events study. Platelet reactivity was tested at baseline, 2 hours, 24 hours, 7 days and 90 days after initial dose, including high on-treatment platelet reactivity (HOPR), which was defined as P2Y12 reaction unit >208, and percentage inhibition of platelet aggregation (IPA). A total of 365 patients were included. There were 199 (54.5%) individuals classified as carriers of CYP2C19 loss-of-function alleles. For carriers and non-carriers, the proportions of HOPR were significantly lower in those with ticagrelor/aspirin compared with those with clopidogrel/aspirin at 2 hours, 24 hours, 7 days, respectively (all p<0.05). IPA was higher at all time points except at baseline in patients with ticagrelor/aspirin compared with those with clopidogrel/aspirin in both carriers and non-carriers of CYP2C19 lose-of-function alleles (all p<0.05). Our findings showed that ticagrelor/aspirin therapy possessed greater platelet inhibition and more rapid onset in platelet inhibition compared with clopidogrel/aspirin therapy both in carriers and non-carriers of CYP2C19 lose-of-function alleles with acute minor stroke or TIA.
| S-EPMC7906170 | biostudies-literature
Project description:Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.
| S-EPMC4101094 | biostudies-literature
Project description:This study aims to determine which factors within the first week after a first-ever transient ischemic attack (TIA) or minor ischemic stroke (MIS) are associated with stroke survivors' ability to return to either partial or full time paid external work (RTpW). In this single-center prospective cohort study, we recruited 88 patients with first-ever TIA or MIS (NIHSS ≤ 5). Bivariate analyses were conducted between patients that did (RTpW) or did not return to paid work (noRTpW) within 7 days after stroke onset and at 3-months follow-up. Then, we conducted multivariate logistic and negative binomial regression analyses assessing (i) which factors are associated with RTpW at 3 months (ii) the likelihood that patients would RTpW at 3 months and (iii) the number of months necessary to RTpW. Overall, 43.2% of the patients did not RTpW at 3 months. At 3-months follow-up, higher anxiety/depression and fatigue-related disabilities were associated with noRTpW. Multivariate analysis showed that higher NIHSS scores at onset and hyperlipidemia (LDL cholesterol > 2.6 mmol/L or statins at stroke onset) were associated with noRTpW at 3 months. Stroke severity and/or newly diagnosed hypercholesterolemia at stroke onset in TIA or MIS patients were associated with not returning to paid work at 3 months.
| S-EPMC9325246 | biostudies-literature
Project description:Background and purposePremature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events.MethodsFifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement.ResultsDuring 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer.ConclusionsSeveral biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies.
| S-EPMC4820048 | biostudies-literature
Project description:ObjectiveTo evaluate the care and outcomes of patients with TIA or minor stroke admitted to the hospital vs discharged from the emergency department (ED).MethodsWe used the Ontario Stroke Registry to create a cohort of patients with minor ischemic stroke/TIA who presented to the hospital April 1, 2008, to March 31, 2009, or April 1, 2010, to March 31, 2011, in the province of Ontario, Canada. We compared processes of care and outcomes (death or recurrent stroke/TIA) in patients admitted to the hospital and discharged with and without stroke prevention clinic follow-up.ResultsIn our sample of 8,540 patients, the use of recommended interventions was highest in admitted patients, followed by discharged patients referred to prevention clinics, followed by those discharged without clinic referral. Eight percent of nonadmitted patients returned to the hospital with recurrent stroke/TIA within 1 week of the index event. One-year stroke case-fatality was similar in admitted and discharged patients (adjusted hazard ratio 1.11; 95% confidence interval 0.92-1.34). Among patients discharged from EDs, referral to a stroke prevention clinic was associated with a markedly lower risk of mortality (adjusted hazard ratio 0.49; 95% confidence interval 0.38-0.64).ConclusionsPatients with minor ischemic stroke or TIA discharged from the ED are less likely than admitted patients to receive timely stroke care interventions. Among discharged patients, referral to a stroke prevention clinic is associated with improved processes of care and lower mortality. Additional strategies are needed to improve access to high-quality outpatient TIA care.
| S-EPMC4844241 | biostudies-literature
Project description:Importance:The timely delivery of guideline-concordant care may reduce the risk of recurrent vascular events for patients with transient ischemic attack (TIA) and minor stroke. Although many health care organizations measure stroke care quality, few evaluate performance for patients with TIA or minor stroke, and most include only a limited subset of guideline-recommended processes. Objective:To assess the quality of guideline-recommended TIA and minor stroke care across the Veterans Health Administration (VHA) system nationwide. Design, Setting, and Participants:This cohort study included 8201 patients with TIA or minor stroke cared for in any VHA emergency department (ED) or inpatient setting during federal fiscal year 2014 (October 1, 2013, through September 31, 2014). Patients with length of stay longer than 6 days, ventilator use, feeding tube use, coma, intensive care unit stay, inpatient rehabilitation stay before discharge, or receipt of thrombolysis were excluded. Outlier facilities for each process of care were identified by constructing 95% CIs around the facility pass rate and national pass rate sites when the 95% CIs did not overlap. Data analysis occurred from January 16, 2016, through June 30, 2017. Main Outcomes and Measures:Ten elements of care were assessed using validated electronic quality measures. Results:In the 8201 patients included in the study (mean [SD] age, 68.8 [11.4] years; 7877 [96.0%] male; 4856 [59.2%] white), performance varied across elements of care: brain imaging by day 2 (6720/7563 [88.9%]; 95% CI, 88.2%-89.6%), antithrombotic use by day 2 (6265/7477 [83.8%]; 95% CI, 83.0%-84.6%), hemoglobin A1c measurement by discharge or within the preceding 120 days (2859/3464 [82.5%]; 95% CI, 81.2%-83.8%), anticoagulation for atrial fibrillation by day 7 after discharge (1003/1222 [82.1%]; 95% CI, 80.0%-84.2%), deep vein thrombosis prophylaxis by day 2 (3253/4346 [74.9%]; 95% CI, 73.6%-76.2%), hypertension control by day 90 after discharge (4292/5979 [71.8%]; 95% CI, 70.7%-72.9%), neurology consultation by day 1 (5521/7823 [70.6%]; 95% CI, 69.6%-71.6%), electrocardiography by day 2 or within 1 day prior (5073/7570 [67.0%]; 95% CI, 65.9%-68.1%), carotid artery imaging by day 2 or within 6 months prior (4923/7685 [64.1%]; 95% CI, 63.0%-65.2%), and moderate- to high-potency statin prescription by day 7 after discharge (3329/7054 [47.2%]; 95% CI, 46.0%-48.4%). Performance varied substantially across facilities (eg, neurology consultation had a facility outlier rate of 53.0%). Performance was higher for admitted patients than for patients cared for only in EDs with the greatest disparity for carotid artery imaging (4478/5927 [75.6%] vs 445/1758 [25.3%]; P < .001). Conclusions and Relevance:This national study of VHA system quality of care for patients with TIA or minor stroke identified opportunities to improve care quality, particularly for patients who were discharged from the ED. Health care systems should engage in ongoing TIA care performance assessment to complement existing stroke performance measurement.
| S-EPMC5885264 | biostudies-literature
Project description:Background and Purpose- While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods- The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results- At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% versus 14.3%; odds ratio, 0.97 [95% CI, 0.82-1.14]; P=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% versus 4.0%; odds ratio, 0.73 [95% CI, 0.53-1.01]; P=0.06) and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% versus 7.4%; odds ratio, 0.78 [95% CI, 0.62-0.99]; P=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% versus 6.0%; odds ratio, 0.74 [95% CI, 0.57-0.96]; P=0.02). In multivariate analysis, age, subsequent ischemic stroke, serious adverse events, and major bleeding were significantly associated with disability in TIA; for those with stroke, female sex, hypertension, or diabetes mellitus, National Institutes of Health Stroke Scale score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions- In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.
| S-EPMC7313376 | biostudies-literature
Project description:BACKGROUND:We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. METHODS AND RESULTS:In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke (P=0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. CONCLUSIONS:Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack.
| S-EPMC5669168 | biostudies-literature
Project description:ImportanceInfarction patterns may serve as important imaging markers to assess the probability of stroke recurrence in transient ischemic attack (TIA) and minor stroke. However, it is unclear whether patients with different infarction patterns benefit differently from dual antiplatelet therapy.ObjectivesTo investigate whether infarction patterns can stratify the risk of recurrent stroke and whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone are consistent in different infarction patterns after TIA or minor stroke.Design, setting, and participantsIn this prespecified imaging substudy of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial, a total of 1342 patients with noncardioembolic TIA or minor stroke at 45 sites of CHANCE from October 1, 2009, to July 30, 2012, were included in this substudy. The final analysis was conducted on July 30, 2016, and included 1089 patients with required magnetic resonance imaging sequences. Infarction patterns were grouped into multiple acute infarctions (MAIs), single acute infarction (SAI), and no acute infarction (NAI) according to diffusion-weighted imaging.Main outcomes and measuresPrimary and secondary efficacy outcomes were stroke recurrence and new clinical vascular event after 3 months, respectively. The safety outcome was moderate to severe bleeding risk after 3 months.ResultsAmong 1089 patients, the mean (SD) age was 63.1 (10.7) years and 731 patients (65%) were men. Patients with MAIs (hazard ratio [HR], 5.8; 95% CI, 2.2-15.1; P < .001) and SAI (HR, 3.9; 95% CI, 1.5-10.5; P = .007) had higher risk of recurrent stroke than those with NAI after adjustment for potential confounders at 3-month follow-up. Stroke recurrence occurred in 15 (10.1%) and 25 (18.8%) of patients with MAIs administered clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 0.5; 95% CI, 0.3-0.96; P = .04), 24 (8.9%) and 24 (8.5%) of patients with SAI administered clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 1.1; 95% CI, 0.6-2.0; P = .71), and 3 (2.6%) and 2 (1.4%) of patients with NAI administered clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 1.7; 95% CI, 0.3-11.1; P = .56), with P = .04 for treatment × infarction pattern interaction effect. Clopidogrel plus aspirin did not increase moderate to severe bleeding risk.Conclusions and relevanceInfarction patterns can efficiently stratify the risk of recurrent stroke within 3 months of noncardioembolic TIA or minor ischemic stroke. Patients with MAIs received the most pronounced clinical benefit from dual antiplatelet therapy without increasing the risk of moderate to severe bleeding. However, even if after dual antiplatelet treatment, patients with MAIs still had a risk of stroke recurrence as high as those with SAI.Trial registrationclinicaltrials.gov Identifier: NCT00979589.
| S-EPMC5885215 | biostudies-literature