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Ticagrelor Versus Clopidogrel in Minor Stroke or Transient Ischemic Attack With Intracranial Artery Stenosis: A Post Hoc Analysis of CHANCE-2.

ABSTRACT: Background This study aimed to investigate the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in Chinese patients by the presence and clinical presentation of intracranial artery stenosis (ICAS) using randomized trial data from the CHANCE-2 (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II) trial. Methods and Results A total of 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles were randomized to either the ticagrelor-aspirin or clopidogrel-aspirin group. Patients without imaging of the intracranial artery were excluded from the nonprespecified subgroup analysis of CHANCE-2. All patients included were classified into the following groups: without ICAS, symptomatic ICAS, or asymptomatic ICAS. The primary efficacy outcome was new strokes within 90 days. There were 5893 patients (median age, 64.8 years; 33.9% women) included, and 172 (4.9%), 171 (10.5%), and 57 (7.7%) cases of new strokes occurred within 90 days in the without ICAS, with symptomatic ICAS, and with asymptomatic ICAS groups, respectively. Ticagrelor-aspirin was associated with reduced risk of new stroke in patients without ICAS (62 [3.5%] versus 110 [6.3%]; hazard ratio [HR], 0.57 [95% CI, 0.41-0.78]) but not in those with symptomatic ICAS (HR, 0.77 [95% CI, 0.56-1.05]) or in those with asymptomatic ICAS (HR, 0.77 [95% CI, 0.43-1.38]) compared with clopidogrel-aspirin (P for interaction=0.14). There were no significant differences in the proportion of severe or moderate bleeding events among different ICAS groups. Conclusions Patients without ICAS received a significantly greater benefit from ticagrelor-aspirin than clopidogrel-aspirin after minor ischemic stroke or transient ischemic attack, and there was no statistically significant difference between treatments in patients with symptomatic ICAS or asymptomatic ICAS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

SUBMITTER: Wang C

PROVIDER: S-EPMC10727397 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Ticagrelor Versus Clopidogrel in Minor Stroke or Transient Ischemic Attack With Intracranial Artery Stenosis: A Post Hoc Analysis of CHANCE-2.

Wang Chunjuan C Jia Weili W Jing Jing J Meng Xia X Wang Anxin A Xu Qin Q Zhang Xinmiao X Pan Yuesong Y Xie Xuewei X Johnston S Claiborne SC Bath Philip M PM Lin Jinxi J Jiang Yong Y Li Hao H Wang Yilong Y Zhao Xingquan X Liu Liping L Li Zixiao Z Wang Yongjun Y

Journal of the American Heart Association 20231027 21

Background This study aimed to investigate the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in Chinese patients by the presence and clinical presentation of intracranial artery stenosis (ICAS) using randomized trial data from the CHANCE-2 (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II) trial. Methods and Results A total of 6412 patients with minor stroke or transient ischemic attack who carried <i>CYP2C19</i> loss-of-function alleles ...[more]

PMID: 37889172

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Project description:ImportanceAsymptomatic intracranial stenosis (ICS) is a frequent finding on imaging results, particularly in the assessment of acute stroke. Although the management of symptomatic ICS is informed by randomized trials, to our knowledge there are few data on the prevalence and prognosis of asymptomatic ICS in patients with stroke and transient ischemic attack (TIA).ObjectiveTo study the age-specific prevalence and prognosis of asymptomatic ICS in a population-based cohort of patients with TIA and minor stroke.Design, setting, and participantsAll patients (predominantly white) recruited to the Oxford Vascular Study (Oxfordshire, England) between March 1, 2011, and March 1, 2018, with TIA and minor ischemic stroke (National Institutes of Health Stroke Scale score, ≤3), irrespective of age, were included (n = 1579). We determined the age-specific prevalence of 50% or more asymptomatic ICS and the associated stroke risk by face-to-face follow-up to 2018 on standard medical treatment without stenting.ExposuresPatients underwent magnetic resonance angiography of the intracranial and cervicocranial arteries, computed tomography angiography if magnetic resonance angiography was contraindicated, or carotid/transcranial Doppler ultrasonography if computed tomography angiography was contraindicated.Main outcomes and measuresThe primary outcomes were the prevalence and prognosis of asymptomatic ICS.ResultsOf 1368 eligible patients (mean [SD] age, 69.2 [13.9] years; 700 men [51.2%]) with intracranial vascular imaging, 426 ICS were identified in 260 patients (19.0%): 58 (4.2%) with only symptomatic ICS, 155 (11.3%) with only asymptomatic ICS, and 47 (3.4%) with both. The prevalence of any asymptomatic ICS increased from 4.8% for patients younger than 70 years to 34.6% for patients 90 years or older (P for trend < .001; odds ratio per decade, 1.96; 95% CI, 1.69-2.27) and was greater than that of 50% or more asymptomatic carotid bifurcation stenosis (202 [14.8%] vs 105 patients [7.2%]; relative risk, 2.04; 95% CI, 1.63-2.55, P < .001). However, the 155 patients with only asymptomatic ICS had no increase in risk of ischemic stroke compared with those with no ICS (unadjusted HR, 1.03, 95% CI, 0.49-2.17), with 8 first recurrent events (5.2%) during 506 patient-years of follow-up and 3 in the territory of the ICS (annualized risk, 0.59%; 95% CI, 0.12-1.73).Conclusions and relevanceThe prevalence of asymptomatic ICS increases with age in white patients with TIA and minor stroke and is greater than that of asymptomatic carotid stenosis, but asymptomatic ICS does not increase the short- or medium-term risk of distal recurrent ischemic stroke for patients receiving standard medical treatment.

Project description:IntroductionPatients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens-namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days.Methods and analysisMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated.Ethics and disseminationNo formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.

Project description:ImportanceDual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack (TIA). However, there is emerging evidence for the use of ticagrelor and aspirin, and the 2 DAPT regimens have not been compared directly.ObjectiveTo compare ticagrelor and aspirin with clopidogrel and aspirin in patients with acute minor ischemic stroke or TIA in the prevention of recurrent strokes or death.Data sourcesMEDLINE, Embase, and Cochrane from database inception until February 2021.Study selectionRandomized clinical trials that enrolled adults with acute minor ischemic stroke or TIA and provided the mentioned interventions within 72 hours of symptom onset, with a minimum follow-up of 30 days.Data extraction and synthesisPRISMA guidelines for network meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. Fixed-effects models were fit using a bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank curve plots were produced.Main outcomes and measuresThe primary outcome was a composite of recurrent stroke or death up to 90 days. Secondary outcomes include major bleeding, mortality, adverse events, and functional disability. A sensitivity analysis was performed at 30 days for the primary outcome.ResultsA total of 4014 citations were screened; 5 randomized clinical trials were included. Data from 22 098 patients were analyzed, including 5517 in the clopidogrel and aspirin arm, 5859 in the ticagrelor and aspirin arm, and 10 722 in the aspirin arm. Both clopidogrel and aspirin (HR, 0.74; 95% CrI, 0.65-0.84) and ticagrelor and aspirin (HR, 0.79; 95% CrI, 0.68-0.91) were superior to aspirin in the prevention of recurrent stroke and death. There was no statistically significant difference between clopidogrel and aspirin compared with ticagrelor and aspirin (HR, 0.94; 95% CrI, 0.78-1.13). Both DAPT regimens had higher rates of major hemorrhage than aspirin alone. Clopidogrel and aspirin was associated with a decreased risk of functional disability compared with aspirin alone (HR, 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR, 0.85; 95% CrI, 0.75-0.97).Conclusions and relevanceDAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.

Project description:BackgroundDual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended as the secondary prevention of minor ischemic stroke or transient ischaemic attack (TIA). However, genetic polymorphisms of CYP2C19 had been identified as the major cause of poor responsiveness to clopidogrel. Ticagrelor, unlike clopidogrel, did not depend on metabolic activation, but it remained unclear whether ticagrelor was superior to clopidogrel in ischemic stroke. We performed a network meta-analysis to compare the efficacy and safety of ticagrelor, clopidogrel, and aspirin in the minor ischemic stroke and TIA populations.MethodsDatabases of Cochrane Library, ClinicalTrials.gov, and PubMed were searched up to June 19, 2023. Randomized controlled trials (RCTs) assessing antiplatelet drugs for minor stroke or TIA were included. Statistical processing was conducted by using multivariate meta-analysis routines of STATA.ResultsSeven RCTs were included involving 41,745 participants. There was no significant difference between the two DAPTs in preventing stroke recurrence (OR, 1.16; 95% CI, 0.93-1.44), ischemic stroke recurrence (OR, 1.16; 95% CI, 0.93-1.45), and major hemorrhage (OR, 1.22; 95% CI, 0.62,2.39). Compared with aspirin alone, the two DAPT regimen reduced the risk of stroke recurrence (clopidogrel: OR, 0.69; 95% CI, 0.60-0.80, ticagrelor: OR, 0.66; 95% CI, 0.49-0.87) and ischemic stroke recurrence, but increased the incidence of major hemorrhage (clopidogrel: OR, 2.05; 95% CI, 1.22- 3.77; ticagrelor: OR, 2.55; 95% CI, 1.25-4.99). Despite being associated with a higher risk of any bleeding, ticagrelor did not impact the composite of vascular events or mortality. While ticagrelor and aspirin reduced the risk of ischemic stroke recurrence (OR, 0.77; 95% CI, 0.63- 0.92) without increasing the risk of major bleeding (OR 0.94; 95% CI 0.45-1.95) in the Asian population mainly Chinese.ConclusionsDAPT was superior to aspirin in stroke prevention, but little difference existed between the two DAPT regimens. Asian population mainly Chinese may benefit from DAPT with aspirin and ticagrelor. But further head-to-head RCTs are needed to validate the study results.

Project description:ImportanceDual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA.ObjectiveTo obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA.Design, setting, and participantsThis analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019.InterventionsIn the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset.Main outcomes and measuresThe primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage.ResultsThe study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant.Conclusions and relevanceIn this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

Project description:Background and Purpose- The role of aspirin plus clopidogrel (A+C) therapy compared with aspirin monotherapy in patients presenting with acute ischemic stroke (IS) or transient ischemic attack remains uncertain. We conducted this study to determine the optimal period of efficacy and safety of A+C compared with aspirin monotherapy. Methods- Ten randomized controlled trials (15 434 patients) were selected using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) (inception June 2018) comparing A+C with aspirin monotherapy in patients with transient ischemic attack or IS. The primary efficacy outcome was recurrent IS, and the primary safety outcome was major bleeding. The secondary outcomes were major adverse cardiovascular events (composite of stroke, myocardial infarction, and cardiovascular mortality) and all-cause mortality. We stratified analysis based on the short- (≤1 month), intermediate- (≤3 month), and long-term (>3 month) A+C therapy. Effects were estimated as relative risk (RR) with 95% CI. Results- A+C significantly reduced the risk of recurrent IS at short-term (RR, 0.53; 95% CI, 0.37-0.78) and intermediate-term (RR, 0.72; 95% CI, 0.58-0.90) durations. Similarly, major adverse cardiovascular event was significantly reduced by short-term (RR, 0.68; 95% CI, 0.60-0.78) and intermediate-term (RR, 0.76; 95% CI, 0.61-0.94) A+C therapy. However, long-term A+C did not yield beneficial effect in terms of recurrent IS (RR, 0.81; 95% CI, 0.63-1.04) and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.71-1.07). Intermediate-term (RR, 2.58; 95% CI, 1.19-5.60) and long-term (RR, 1.87; 95% CI, 1.36-2.56) A+C regimens significantly increased the risk of major bleeding as opposed to short-term A+C (RR, 1.82; 95% CI, 0.91-3.62). Excessive all-cause mortality was limited to long-term A+C (RR, 1.45; 95% CI, 1.10-1.93). Conclusions- Short-term A+C is more effective and equally safe in comparison to aspirin alone in patients with acute IS or transient ischemic attack.

Dataset Information

Ticagrelor Versus Clopidogrel in Minor Stroke or Transient Ischemic Attack With Intracranial Artery Stenosis: A Post Hoc Analysis of CHANCE-2.

Publications

Ticagrelor Versus Clopidogrel in Minor Stroke or Transient Ischemic Attack With Intracranial Artery Stenosis: A Post Hoc Analysis of CHANCE-2.

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