ticagrelor and Ischemic-Attack--Transient

Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors.. The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I2 statistics to assess statistical heterogeneity.. This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81-0.99, p = 0.03; I2 = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74-0.90, p < 0.0001; I2 = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84-1.06, p = 0.31; I2 = 62%), major bleeding (OR: 1.06; 95% CI: 0.97-1.15, p = 0.20; I2 = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76-1.96, p = 0.41; I2 = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78-1.43, p = 0.71; I2 = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19-1.66, p < 0.0001; I2 = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75-0.93, p = 0.0009; I2 = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71-0.89, p < 0.0001; I2 = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes.. Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Dual 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.. Databases 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.. Seven 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.. DAPT 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.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Antiplatelet therapy is the first-line management for noncardioembolic transient ischemic attack (TIA) and acute ischemic stroke (IS). Herein, we review the safety and efficacy of antiplatelet therapies in patients with IS and TIA, primarily focusing on the acute stage. We discuss current antiplatelet monotherapy and the factors influencing efficacy and continuation rate according to clinical trial data. Aspirin remains the most commonly used first-line antiplatelet agent for preventing noncardioembolic stroke recurrence, and clopidogrel, cilostazol, and ticagrelor are feasible alternatives. Various short-term dual antiplatelet therapies (including clopidogrel-aspirin and ticagrelor-aspirin combination therapy) for minor stroke and high-risk TIA are also reviewed. For selected patients with specific stroke etiologies, short-term dual antiplatelet therapy with aspirin combined with clopidogrel or ticagrelor can significantly reduce the risk of stroke. However, insufficient evidence supports the benefits of triple antiplatelet therapy for recurrent noncardioembolic stroke prevention, and this treatment substantially increases the rate of bleeding complications. Keyword: antiplatelet therapy, acute ischemic stroke, secondary prevention, transient ischemic attack.

Topics: Aspirin; Cerebral Infarction; Clopidogrel; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticagrelor

Dual 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.. To 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.. MEDLINE, Embase, and Cochrane from database inception until February 2021.. Randomized 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.. PRISMA 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.. The 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.. A 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).. DAPT 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.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Ticagrelor

In recent randomized controlled studies, the prevention of stroke and cognitive function of ticagrelor has been controversial. We conducted a meta-analysis to compare ticagrelor with other antiplatelet treatment in patients with vascular high-risk factors disease, defined as acute coronary syndrome, stroke or transient ischemic attack, coronary artery disease or peripheral artery disease.. We searched the PubMed, Embase, and Cochrane libraries for published randomized controlled trials and additional available data from ClinicalTrials.gov. The primary outcome was related adverse stroke events and the secondary outcome was cognitive function related adverse events. The outcomes were statistically analyzed using Peto odds ratio.. 12 RCTs with 105,654 patients were included in meta-analysis.. all stroke (OR 0.84, 95%CI 0.78-0.90, P < 0.001); Secondary outcomes: ischemic stroke (OR 0.83, 95%CI 0.77-0.90, P < 0.001), transient ischemic attack (OR 0.78, 95%CI 0.62-0.97, P = 0.029), intracranial hemorrhage (OR 1.33, 95%CI 1.09-1.61, P = 0.005), Parkinson's disease (OR 0.30, 95%CI 0.12-0.72, P = 0.007), dementia (OR 0.31, 95%CI 0.13-0.77, P = 0.012), dizziness (OR: 1.39, 95%CI 1.03-1.87, P = 0.032), insomnia (OR 1.45, 95%CI 1.05-2.00, P = 0.026).. Ticagrelor may provide more favorable outcomes for all stroke, ischemic stroke, and transient ischemic attack prevention in patients with vascular high-risk factors. However, this benefit may come with the cost of intracranial hemorrhage, dizziness and insomnia. Ticagrelor may reduce the risk of dementia and Parkinson's disease, although available data are limited.

Topics: Cognitive Dysfunction; Dementia; Dizziness; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Parkinson Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Stroke; Ticagrelor

Topics: Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Aspirin is a cornerstone of preventive treatment for stroke recurrence, but during the last few years the role of dual antiplatelet therapy (DAPT) is much more emerging.. This systematic review aimed to compare early use of P2Y12 inhibitors (clopidogrel/ticagrelor) plus aspirin to aspirin alone for acute treatment and secondary prevention in acute non-cardioembolic minor ischemic stroke or TIA.. A systematic search on MEDLINE and EMBASE was performed. Treatment effects were estimated with RRs and 95% CI. We used RevMan 5.4 for data analyses. We assessed methodological quality of selected studies according to Rob2 tools and quality of evidence with GRADE approach.. Four RCTs were included, enrolling 21,459 patients. Compared to aspirin alone, DAPT was superior in reducing stroke recurrence (RR 0.74, 95% CI 0.67-0.82, P <0.00001, absolute risk difference by 2%, NNT 50) and disabling stroke defined as mRS>2 (RR 0.84, 95% CI 0.75-0.95, P = 0.004), with no impact on all causes of mortality (RR 1.30, 95% CI 0.90-1.89, P = 0.16). An increased risk of major bleeding was emerged (RR 2.54, 95% CI 1.65-3.92, P <0.0001, absolute risk difference by 0,4%, NNH 250), in particular with ticagrelor, but there was no correlation between therapy duration and bleeding risk, as appeared from one-month (RR 3.06, 95% CI 1.64 to 5.69) and three-month (RR 2.09, 95% CI 1.18 to 3.69) follow-up analysis.. Early administration of P2Y12 inhibitors plus aspirin in patients with acute non-cardioembolic minor ischemic stroke or TIA reduced the incidence of ischemic stroke recurrence, impacting more significantly than the increased bleeding risk and influencing patients' quality of life by reducing disabling stroke.

Topics: Aspirin; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Quality of Life; Secondary Prevention; Stroke; Ticagrelor

Antiplatelet therapy is one of the mainstays for secondary stroke prevention. This narrative review aimed to highlight the current evidence and recommendations of antiplatelet therapy for stroke prevention.We conducted advanced literature search for antiplatelet therapy. Landmark studies and randomised controlled trials evaluating antiplatelet therapy for secondary stroke prevention are reviewed. Results from Cochrane systematic review, pooled data analysis and meta-analysis are discussed.Single-antiplatelet therapy (SAPT) with aspirin, aspirin/extended-release dipyridamole or clopidogrel reduces the risk of recurrent ischaemic stroke in patients with non-cardioembolic ischaemic stroke or transient ischaemic attack (TIA). Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute noncardioembolic ischaemic stroke or high-risk TIA. Prolonged use of DAPT is associated with higher risk of haemorrhage without reduction in stroke recurrence than SAPT. Compared with placebo, aspirin reduces the relative risk of recurrent stroke by approximately 22%. Aspirin/dipyridamole and cilostazol are superior to aspirin but associated with significant side effects. Cilostazol or ticagrelor might be more effective than aspirin or clopidogrel in patients with intracranial stenosis.SAPT is indicated for secondary stroke prevention in patients with non-cardioembolic ischaemic stroke or TIA. DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days followed by SAPT is recommended for patients with minor acute noncardioembolic stroke or high-risk TIA. Selection of appropriate antiplatelet therapy should also be based on compliance, drug tolerance or resistance.

Topics: Aspirin; Brain Ischemia; Cilostazol; Clopidogrel; Dipyridamole; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Antiplatelet therapy is key to prevent recurrences in patients with an acute or prior non-cardioembolic stroke or transient ischemic attack (TIA). The narrow balance between the risks of ischemic recurrence and major bleeding is a relevant clinical dilemma in this population.. This review covers the current evidence on antiplatelet therapy for patients with non-cardioembolic stroke or TIA. Randomized controlled trials of antithrombotic strategies for patients with these conditions were searched in Pubmed/Medline from 1970 to 2022.. Numerous randomized controlled trials have defined the current indications to the use of antiplatelet drugs for patients with non-cardioembolic ischemic stroke or TIA. For the management of these subjects, single antiplatelet therapy with aspirin or clopidogrel, or the combination of aspirin and dipyridamole, is usually recommended. After an acute stroke or TIA, a short course of dual antiplatelet therapy with aspirin in combination with clopidogrel or ticagrelor should be considered. The risk of bleeding might be higher with ticagrelor, but a direct comparison with clopidogrel is not available in this setting. The introduction of newer strategies, such as dual-pathway inhibition with aspirin and a direct oral anticoagulant (including emerging factor XI inhibitors under clinical development) may open a new research avenue in this challenging area.

Topics: Anticoagulants; Aspirin; Clopidogrel; Dipyridamole; Drug Therapy, Combination; Factor XI; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Antiplatelet therapy is the cornerstone for acute ischemic stroke or transient ischemic attack (TIA). The purpose of this study was to conduct a meta-analysis to assess the efficacy and safety of P2Y12 receptor inhibitor plus aspirin versus aspirin alone treated within 24 h after acute noncardioembolic ischemic stroke or TIA.. We search Pubmed, EMBASE, CENTRAL and clinicaltrials.gov from January 1966 to January 2021. We included randomized trials which compared P2Y12 receptor inhibitor plus aspirin versus aspirin alone. Relative risk (RR) with 95% confidence (CI) was used as a measure of P2Y12 receptor inhibitor plus aspirin versus aspirin. The primary efficacy endpoint was recurrent stroke and the primary safety endpoint was severe bleeding.. The search identified 5 randomized trials comparing P2Y12 receptor inhibitor plus aspirin and aspirin with 21,808 individuals enrolled. Pooled results from these trials showed that P2Y12 receptor inhibitor plus aspirin compared with aspirin was associated with a lower risk of recurrent stroke (RR 0.75, 95% CI 0.68 to 0.83). Ticagrelor plus aspirin compared with aspirin was associated with increased risk of severe bleeding (RR 3.98, 95% CI 1.74 to 9.10) and intracranial hemorrhage (RR 3.32, 95% CI 1.33 to 8.25), whereas clopidogrel plus aspirin vs. aspirin had similar hemorrhagic risk.. P2Y12 receptor inhibitor plus aspirin vs aspirin given within 24 h after acute noncardioembolic ischemic stroke or TIA reduces the risk of subsequent stroke. However, the risk of severe bleeding, including intracranial hemorrhage, was higher with ticagrelor plus aspirin vs aspirin.. CRD42020203730.

Topics: Aspirin; Cerebral Infarction; Drug Therapy, Combination; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor

Patients 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.. MEDLINE, 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.. No 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.

Topics: Aspirin; Bayes Theorem; Brain Ischemia; Clopidogrel; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Ticagrelor

The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (<24 hours) of DAPT (using either clopidogrel or ticagrelor with aspirin) versus single antiplatelet therapy (SAPT; aspirin alone) in acute non-cardioembolic ischemic stroke or TIA, incorporating data from large randomized controlled trials. Published trials fulfilling our criteria were identified from an electronic search of MEDLINE, with key words including: "clopidogrel or ticagrelor", "aspirin", "ischemic stroke", "transient ischemic attack", and "randomized controlled trial". Included were 3 randomized controlled trials of 21,067 patients assessing early administration (<24 hours from symptom onset) of DAPT versus SAPT in non-cardioembolic acute ischemic stroke or TIA. Our efficacy outcomes were ischemic stroke and all-cause mortality. Our safety outcome was severe bleeding. We performed a meta-analysis to pool results with a hierarchical Bayesian random-effects model. Dual antiplatelet therapy significantly reduced the risk of ischemic stroke (hazard ratio [HR], 0.73; 95% credible interval [CrI]: 0.54, 0.97), while increasing the risk of severe bleeding (HR, 2.48; 95% CrI: 1.07, 5.26). There was a non-significant numerical trend toward increased mortality with DAPT (HR, 1.29; 95% CrI: 0.73, 2.23). These observations were robust under the sensitivity analysis. In the present systematic review and meta-analysis of randomized controlled trials, DAPT reduced the risk of ischemic stroke at the cost of an increase in severe bleeding. Additional trials examining the ideal timing of DAPT administration are needed to thoroughly investigate the role, if any, of routine DAPT in patients with non-cardioembolic ischemic stroke or high-risk TIA.

Topics: Aspirin; Clopidogrel; Dual Anti-Platelet Therapy; Early Medical Intervention; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Mortality; Platelet Aggregation Inhibitors; Proportional Hazards Models; Secondary Prevention; Ticagrelor

Topics: Aspirin; Clopidogrel; Drug Resistance; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Risk Assessment; Secondary Prevention; Severity of Illness Index; Ticagrelor

Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis.. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model.. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit.. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke.

Topics: Adenosine; Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Proportional Hazards Models; Recurrence; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine; Treatment Failure

The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included.. In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73-0.88; P<0.0001; I(2)=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69-0.85; P<0.0001; I(2)=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68-0.86; P<0.0001; I(2)=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke.. DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75-100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes.. http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.

Topics: Adenosine; Aged; Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Clopidogrel; Cohort Studies; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Population; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Secondary Prevention; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Vascular Diseases

The new definition and risk stratification for transient ischemic attack (TIA) have clear implications for the urgency of evaluation and treatment. The optimal antithrombotic treatment for TIA is being intensively studied. New guidelines for prevention of non-cardioembolic stroke in patients with stroke or TIA recommend the use of antiplatelet agents rather than oral anticoagulation. New antiplatelet drugs are being used in cardiovascular patients, and their role in cerebrovascular patients is being studied. The impact of genetic CYP2C19 polymorphisms is becoming clarified in cardiovascular patients and it is likely these polymorphisms will affect the management of cerebrovascular patients. The results of trials of clopidogrel plus aspirin in patients with lacunar strokes and acute TIAs are forthcoming. The results of CLOSURE I, a study of a patent foramen ovale device closure trial for cryptogenic stroke or TIA, showed no differences in stroke or TIA at 2 years.

Topics: Adenosine; Aryl Hydrocarbon Hydroxylases; Brain Ischemia; Cilostazol; Clinical Trials as Topic; Clopidogrel; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Fibrinolytic Agents; Foramen Ovale, Patent; Genotype; Humans; Ischemic Attack, Transient; Piperazines; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; Stroke; Tetrazoles; Thiophenes; Ticagrelor; Ticlopidine

Ticagrelor is one of the most recent antiplatelet drugs to be approved to treat ischemic heart disease. Its efficacy may exceed aspirin in improving clinical outcomes in patients with acute ischemic stroke who are ineligible for rt-PA.. We evaluated the safety regarding hemorrhagic complications (as a primary endpoint) and the efficacy (as a secondary endpoint) of a 180-mg loading dose of ticagrelor given within 9 h from the onset of the first-ever non-cardioembolic ischemic stroke.. We conducted our study on patients aged 18-75 years who presented with their first clinically manifested non-cardioembolic ischemic stroke and were recruited from the emergency department OF Kafr El-Sheik University Hospitals, Egypt. Eligible patients randomly received ticagrelor or aspirin loading and maintenance doses. Screening, randomization, and initiation of treatment all occurred within the first 9 h of stroke onset.. Eighty-five patients received ticagrelor, and 84 received aspirin. Patients who received ticagrelor had a better clinical outcome in terms of NIHSS improvement at 2 days and 1 week of discharge and a favorable mRS score after 1 week of discharge and at 90-day follow-up. There was no significant difference between the two groups regarding hemorrhagic adverse effects.. This pilot study found that ticagrelor had a better clinical outcome than aspirin based on NIHSS and mRS in acute ischemic stroke patients who received it within 9 h from symptom onset and had a shorter hospital stay duration. Ticagrelor was non-inferior to aspirin regarding hemorrhagic complications.. We registered our trial on ClinicalTrials.gov, named after "ticagrelor versus aspirin in ischemic stroke," and with a clinical trial number (NCT03884530)-March 21, 2019.

Topics: Aspirin; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Ischemic Stroke; Pilot Projects; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

This study was performed to investigate whether ticagrelor/aspirin versus clopidogrel/aspirin can further reduce the residual risk of stroke recurrence in patients with positive diffusion-weighted imaging (DWI) in the High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial.. Patients with DWI data in the CHANCE-2 trial were included and divided into those with and without acute infarction according to their DWI findings. The primary efficacy outcome and safety outcome were stroke recurrence and moderate to severe bleeding within 3 months of follow-up, respectively.. Of the 6,412 patients enrolled in the CHANCE-2 trial, 5,796 (90.4%) patients with DWI data were included in the subgroup analysis. A total of 4,369 patients (75.4%) had an acute infarction on DWI. Patients with positive DWI had higher risk of recurrent stroke (8.1%) than those without infarction (2.2%) within 3-month follow-up. Compared with clopidogrel/aspirin, ticagrelor/aspirin was associated with lower risk of stroke in patients with positive DWI (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.52-0.80, p < 0.001) than in those negative DWI (HR = 1.22, 95% CI = 0.55-2.72, p = 0.63), with a significant interaction association (p for interaction = 0.049). The risk of moderate to severe bleeding was similar between ticagrelor/aspirin and clopidogrel/aspirin treatment in the different groups.. Our study demonstrates that imaging evaluation should be emphasized before targeting the best candidates for genotype-guided dual antiplatelet therapy in future clinical research and practice. ANN NEUROL 2023;93:783-792.

Topics: Aspirin; Cerebral Infarction; Clopidogrel; Drug Therapy, Combination; Genotype; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct (ACI) after minor stroke or transient ischemic attack.. Data were obtained from the double-blind CHANCE-2 trial (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II), which was conducted across 202 centers in China from September 2019 to March 2021. Patients with positive diffusion-weighted imaging were included and classified into PCI and ACI groups according to the hyperintense lesions on diffusion-weighted imaging. The primary efficacy and safety outcomes were a new stroke and severe or moderate bleeding within 90 days, respectively.. A total of 4168 patients were included in this substudy, with 1427 PCI and 2741 ACI. During the 90-day follow-up, the risk of stroke recurrence in patients with PCI was similar to that with ACI (7.4% versus 8.3%; adjusted hazard ratio, 1.01 [95% CI, 0.79-1.29];. Our study demonstrated that stroke recurrence was similar between PCI and ACI in patients with minor stroke or transient ischemic attack. Additionally, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke within 90 days in both PCI and ACI patients.. URL: https://www.. gov; Unique identifier: NCT04078737.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Infarction; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19 loss-of-function (LOF) alleles after a transient ischemic attack (TIA) or minor ischemic stroke. However, the association between the degree of CYP2C19 LOF and ideal treatment allocation remains unknown.. To investigate whether the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin are consistent with the expected degree of CYP2C19 LOF after TIA or minor stroke.. CHANCE-2 was a multicenter, double-blind, double-dummy, placebo-controlled randomized clinical trial. Patients were enrolled at 202 centers in China from September 23, 2019, through March 22, 2021. Patients with at least two *2 or *3 alleles (*2/*2, *2/*3, or *3/*3) according to point-of-care genotyping were classified as "poor metabolizers," and those with one *2 or *3 allele (*1/*2 or *1/*3) were classified as "intermediate metabolizers.". Patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or clopidogrel (300-mg loading dose on day 1 followed by 75 mg/d for days 2-90). All patients received aspirin (75- to 300-mg loading dose followed by 75 mg/d for 21 days).. The primary efficacy outcome was a new ischemic or hemorrhagic stroke. The secondary efficacy outcome was a composite of new clinical vascular events and individual ischemic stroke events within 3 months. The primary safety outcome was severe or moderate bleeding. Analyses were performed according to the intention-to-treat principle.. Of the 6412 patients enrolled, the median age was 64.8 years (IQR, 57.0-71.4 years), and 4242 patients (66.2%) were men. Of the 6412 patients, 5001 (78.0%) were intermediate metabolizers, and 1411 (22.0%) were poor metabolizers. The primary outcome occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status (6.0% [150 of 2486] vs 7.6% [191 of 2515]; hazard ratio [HR], 0.78 [95% CI, 0.63-0.97] among intermediate metabolizers and 5.7% [41 of 719] vs 7.5% [52 of 692]; HR, 0.77 [95% CI, 0.50-1.18] among poor metabolizers; P = .88 for interaction). Patients taking ticagrelor-aspirin had a higher risk of any bleeding event compared with those taking clopidogrel-aspirin, irrespective of metabolizer status: 5.4% (134 of 2486) vs 2.6% (66 of 2512) (HR, 2.14 [95% CI, 1.59-2.89]) among intermediate metabolizers and 5.0% (36 of 719) vs 2.0% (14 of 692) (HR, 2.99 [95% CI, 1.51-5.93]) among poor metabolizers (P = .66 for interaction).. This prespecified analysis of a randomized clinical trial found no difference in treatment effect between poor and intermediate CYP2C19 metabolizers. The relative clinical efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin were consistent across CYP2C19 genotypes.. ClinicalTrials.gov Identifier: NCT04078737.

Topics: Aged; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; East Asian People; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Body mass index (BMI) may affect the response to platelet P2Y. In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we randomized patients with minor stroke or TIA who carried the. Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel-ASA, ticagrelor-ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69-1.04) The interaction of treatment and BMI group was significant (. In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel-ASA, patients with obesity received more clinical benefit from ticagrelor-ASA therapy than those without obesity.. Clinicaltrials.gov, no. NCT04078737.

Topics: Aspirin; Body Mass Index; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Obesity; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Topics: Arteries; Aspirin; Clopidogrel; Constriction, Pathologic; Drug Therapy, Combination; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Ticagrelor is one of the most recent antiplatelet drugs used to treat ischemic heart disease. Its efficacy may equal or exceed aspirin in improving clinical outcomes in patients with acute ischemic stroke who are ineligible for rt-PA.. We aimed at evaluating the safety (as a primary endpoint) and efficacy (as a secondary endpoint) of a 180 mg loading dose of ticagrelor given within 9 h from the onset of first-ever ischemic stroke.. We conducted an open-label, randomized prospective controlled clinical trial between May 2019 and September 2020 on patients who presented with their first-ever ischemic stroke and were recruited from the emergency department, of Kafr el-sheik University Hospitals, Egypt. Eligible patients randomly received aspirin or ticagrelor loading and maintenance doses. Treatment began within 9 h of stroke onset.. Aspirin was given to 84 patients; ticagrelor was given to 85. There was no significant difference between the 2 groups regarding the hemorrhagic and nonhemorrhagic complications. Patients who received ticagrelor had a better outcome regarding NIHSS improvement at 2 days and 1 week or discharge and a favorable mRS score after 1 week or discharge and at 90-day follow-up.. Ticagrelor was noninferior to aspirin regarding safety profile. Compared with aspirin, ticagrelor had a better clinical outcome based on NIHSS and mRS in first-ever acute ischemic stroke patients who received it within 9 h from symptom onset, leading to a shorter hospital stay.

Topics: Humans; Ischemic Attack, Transient; Ischemic Stroke; Pilot Projects; Platelet Aggregation Inhibitors; Prospective Studies; Secondary Prevention; Stroke; Ticagrelor; Treatment Outcome

Hypertension is a risk factor of poor stroke outcomes and associated with antiplatelet resistance. This study aimed to explore the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in patients with different hypertension status, using randomized trial data from the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II).. A total of 6412 patients with minor stroke or transient ischemic attack who carried. Ticagrelor-aspirin was associated with reduced risk of new stroke in patients without hypertension (32 [4.8%] versus 60 [7.2%]; hazard ratio, 0.55 [95% CI, 0.35-0.86]), but not in those with a newly diagnosed hypertension (20 [5.3%] versus 36 [9.1%]; hazard ratio 0.59 [95% CI, 0.33-1.07]), or those with a previously diagnosed hypertension (139 [7.0%] versus 147 [7.4%]; hazard ratio, 0.93 [95% CI, 0.74-1.18]) compared with clopidogrel-aspirin (. In the CHANCE-2 trial, patients without hypertension received a significantly greater benefit from ticagrelor- aspirin than those with previous hypertension after minor stroke or transient ischemic attack, and a similar benefit trend was observed in those with newly diagnosed hypertension.. URL: https://www.. gov; Unique identifier: NCT04078737.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Hypertension; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy (DAPT) with ticagrelor and aspirin has been found to be effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA) in individuals who carry CYP2C19 loss-of-function (LOF) alleles; however, uncertainties remain about the time course of benefit and risk with ticagrelor and aspirin in these patients.. To obtain time-course estimates of efficacy and risk with ticagrelor and aspirin after minor stroke or TIA in individuals with CYP2C19 LOF alleles.. The Ticagrelor or Clopidogrel With Aspirin in High-risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) randomized clinical trial enrolled patients 40 years and older from 202 hospitals in China with acute minor stroke or TIA who carried CYP2C19 LOF alleles between September 23, 2019, and March 22, 2021, and were followed up for 90 days. All 6412 patients enrolled in the CHANCE-2 trial were included in this secondary analysis. Data were analyzed in October 2021.. Ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2-90) or clopidogrel (300 mg on day 1 followed by 75 mg daily on days 2-90). All patients received aspirin (75-300 mg on day 1 followed by 75 mg daily for 21 days).. The efficacy outcome was major ischemic event, defined as the composite of ischemic stroke or nonhemorrhagic death. Safety outcomes included moderate to severe bleeding and any bleeding.. A total of 6412 patients were included (3205 in the ticagrelor and aspirin group and 3207 in the clopidogrel and aspirin group). The median (IQR) age was 65 (57-71) years, and 4242 patients (66%) were men. The reduction of major ischemic events with ticagrelor and aspirin predominately occurred in the first week (absolute risk reduction, 1.34%; 95% CI, 0.29 to 2.39) and attenuated but remained in the next 3 weeks (absolute risk reduction in the second week, 0.11%; 95% CI, -0.24 to 0.45; absolute risk reduction in the third week, 0.14%; 95% CI, -0.11 to 0.38; absolute risk reduction in the fourth week, 0.04%; 95% CI, -0.18 to 0.25). The risk of moderate to severe bleeding was consistently low in the ticagrelor and aspirin group. The absolute increase in any bleeding seen in the first week (0.87%; 95% CI, 0.25 to 1.50) remained in the next 3 weeks (absolute increase in the second week, 1.21%; 95% CI, 0.75 to 1.68; absolute increase in the third week, 0.33%; 95% CI, -0.05 to 0.72; absolute increase in the fourth week, 0.23%; 95% CI, -0.03 to 0.49).. Among patients with minor stroke or TIA who carried CYP2C19 LOF alleles, benefit with ticagrelor and aspirin was present predominately in the first week, with additional small benefit accruing in the next 2 weeks.

Topics: Aged; Alleles; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial.. Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y. In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit.. In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points.. In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%–2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%–0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%–1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups.. In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage.. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.

Topics: Adult; Aged; Aspirin; Cerebral Hemorrhage; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Ticagrelor

Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in. We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried. A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively.. Among Chinese patients with minor ischemic stroke or TIA who were carriers of

Topics: Aged; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Incidence; Ischemic Attack, Transient; Ischemic Stroke; Loss of Function Mutation; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Ticagrelor

It remains unclear whether smoking status has an impact on platelet reactivity and clinical outcomes of ticagrelor versus clopidogrel in patients with acute minor stroke or transient ischaemic attack (TIA).. A subgroup analysis of a randomized controlled trial was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by VerifyNow P2Y12 assay at baseline, 7 + 2 days and 90 ± 7 days. High on-treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208. Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days. Patients who smoked one or more cigarettes per day for at least 1 year in their lives were defined as smokers.. Of 675 patients enrolled in the trial, 370 patients (54.8%) were smokers. At 7 + 2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% vs. 21.8%) and non-smokers (2.3% vs. 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR (P = 0.058). At 90 ± 7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers: 7.0% vs. 4.9%; hazard ratio, 1.57; 95% confidence interval, 0.65-3.79; P = 0.39; non-smokers: 5.3% vs. 13.5%; hazard ratio, 0.39; 95% confidence interval, 0.17-0.91; P = 0.01; P for interaction = 0.02).. Among patients with minor stroke or TIA, ticagrelor was superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of new stroke, particularly for non-smokers.

Topics: Clopidogrel; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Smoking; Stroke; Ticagrelor

Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.. We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.. A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).. Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).

Topics: Aged; Aged, 80 and over; Aspirin; Disability Evaluation; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor

In patients with acute cerebral ischemia, the rate of stroke, myocardial infarction, or death during 90 days was reported to be non-significantly lower with ticagrelor compared with aspirin, with no increase in major hemorrhage. Dual antiplatelet therapy may be more effective in this setting.. To investigate whether ticagrelor combined with aspirin are superior to aspirin alone in preventing stroke or death in patients with non-severe, non-cardioembolic ischemic stroke or high-risk transient ischemic attack.. The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) trial is a randomized, placebo-controlled, double-blind, event-driven study. Patients will be randomized within 24 h of onset of acute ischemic symptoms. THALES is expected to randomize 13,000 at ∼450 sites worldwide, to collect 764 primary outcome events. Study treatments are ticagrelor 180 mg loading dose on day 1, then 90 mg twice daily on days 2-30, or matching placebo. All patients will also receive open-label aspirin 300-325 mg on day 1, then 75-100 mg once daily on days 2-30.. The primary efficacy outcome is time to the composite endpoint of stroke or death through 30-day follow-up. The primary safety outcome is time to first severe bleeding event.. The THALES trial will provide important information about the benefits and risks of dual antiplatelet therapy with ticagrelor and aspirin in patients with acute cerebral ischemia in a global setting (funding: AstraZeneca).. http://www.clinicaltrials.gov . Unique identifier: NCT03354429.

Topics: Aged; Aged, 80 and over; Aspirin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Research Design; Stroke; Ticagrelor

Background and Purpose- Recurrent ischemia risk is high in the acute period after cerebral ischemic events. Effects of antiplatelet agents may vary by time to loading dose (TLD). We explored the risk of recurrent events and safety and efficacy of ticagrelor versus aspirin in relation to TLD. Methods- We randomized 13 199 patients with noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to 90-day ticagrelor or aspirin treatment within 24 hours of symptom onset. For this analysis, 13 126 patients were categorized by TLD as <12 hours or ≥12 hours from start of index event. The primary end point was the composite of stroke, myocardial infarction, or death within 90 days. Major bleeding was the primary safety end point. Results- TLD was <12 hours in 4403 (33.5%) and ≥12 hours in 8723 (66.5%). The Kaplan-Meier% for the primary end point for all patients with TLD<12 hours was 7.5% versus 6.9% in TLD≥12 hours. Among patients with TLD<12 hours, the primary end point occurred in 147/2196 (6.8%) randomized to ticagrelor and in 184/2207 (8.3%) randomized to aspirin (hazard ratio, 0.79; 95% CI, 0.64-0.98; P=0.036). Among patients with TLD≥12 hours, the primary end point occurred in 6.7% patients randomized to ticagrelor versus 7.0% to aspirin (hazard ratio, 0.95; 95% CI, 0.81-1.12; P=0.55). There was no significant treatment-by-TLD interaction. Major bleeding rates were comparable on ticagrelor and aspirin, regardless of TLD. Conclusions- The event rate for the primary end point was higher in patients treated early (<12 hours) versus later (≥12 hours). In this exploratory analysis, a larger numerical difference in the primary end point was observed among patients on ticagrelor than on aspirin when TLD was <12 hours compared with ≥12 hours, although the interaction terms for treatment-by-TLD were not significant. For major bleeding, no relation to TLD was observed. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Topics: Aged; Aged, 80 and over; Aspirin; Endpoint Determination; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Recurrence; Risk; Stroke; Ticagrelor; Time-to-Treatment

Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited.. This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators.. SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages.. The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78-1.01) when calculated on adjudicator-assessed events and 0.88 (0.78-1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75-0.99) based on the adjudicators' diagnoses and 0.85 (0.75-0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%.. In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication.. ClinicalTrials.gov Identifier: NCT01994720.

Topics: Aspirin; Hemorrhage; Humans; Ischemic Attack, Transient; Mortality; Myocardial Infarction; Observer Variation; Platelet Aggregation Inhibitors; Proportional Hazards Models; Research Personnel; Secondary Prevention; Stroke; Ticagrelor

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registr

Topics: Aged; Clopidogrel; Double-Blind Method; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Peripheral Arterial Disease; Stroke; Ticagrelor

Antiplatelet therapy combining aspirin and clopidogrel is considered to be a key intervention for acute ischaemic minor stroke (AIMS) and transient ischaemic attack (TIA). However, the interindividual variability in response to clopidogrel resulting from the polymorphisms in clopidogrel metabolism-related genes has greatly limited its efficacy. To date, there are no reports on individualised antiplatelet therapy for AIMS and TIA based on the genetic testing and clinical features. Therefore, we conduct this randomised controlled trial to validate the hypothesis that the individualised antiplatelet therapy selected on the basis of a combination of genetic information and clinical features would lead to better clinical outcomes compared with the standard care based only on clinical features in patients with AIMS or TIA.. This trial will recruit 2382 patients with AIMS or TIA who meet eligibility criteria. Patients are randomly assigned in a 1:1 ratio to pharmacogenetic group and standard group. Both groups receive a loading dose of 300 mg aspirin and 300 mg clopidogrel on day 1, followed by 100 mg aspirin per day on days 2-365. The P2Y12 receptor antagonist is selected by the clinician according to the genetic information and clinical features for pharmacogenetic group and clinical features for the standard group on days 2-21. The primary efficacy endpoint is a new stroke event (ischaemic or haemorrhagic) that happens within 1 year. The secondary efficacy endpoint is analysed as the individual or composite outcomes of the new clinical vascular event (ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death). Baseline characteristics and outcomes after treatment will be evaluated.. This protocol has been approved by the ethics committee of Yangpu Hospital, Tongji University School of Medicine (No. LL-2018-KY-012). We will submit the results of this trial for publication in a peer-reviewed journal.. ChiCTR1800019911; Pre-results.

Topics: Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticagrelor

Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial. The required sample size was 952 patients. It was registered with ClinicalTrials.gov (NCT02506140). Study outcomes The primary outcome was the proportion of patients with high on-treatment platelet reactivity at 90 days. High on-treatment platelet reactivity is defined as the P2Y12 reaction unit >208 measured using the VerifyNow P2Y12 assay. Conclusion The Platelet Reactivity in Acute Non-disabling Cerebrovascular Events study explored whether ticagrelor combined with aspirin could reduce further the proportion of patients with high on-treatment platelet reactivity at 90 days after acute minor stroke or transient ischemic attack compared with clopidogrel and aspirin.

Topics: Adenosine; Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Heterozygote; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Research Design; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis.. We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.. In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca).. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Topics: Adenosine; Aged; Aortic Diseases; Aspirin; Atherosclerosis; Carotid Stenosis; Female; Humans; Intracranial Embolism; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Recurrence; Stroke; Ticagrelor; Treatment Outcome

In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis.. Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model.. A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61).. The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Topics: Adenosine; Aged; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Aspirin; Cohort Studies; Double-Blind Method; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Treatment Outcome

Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial.. SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720.. Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0·88]; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 [0·84-1·13]; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group.. In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention.. AstraZeneca.

Topics: Adenosine; Adult; Aged; Aspirin; Atherosclerosis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibrinolytic Agents; Humans; International Cooperation; Ischemic Attack, Transient; Male; Middle Aged; Proportional Hazards Models; Stroke; Ticagrelor; Treatment Outcome

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Topics: Adenosine; Aged; Aspirin; Double-Blind Method; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor

The risk of recurrent ischemia is high in the acute period after ischemic stroke and transient ischemic attack. Aspirin is recommended by guidelines for this indication, but more intensive antiplatelet therapy may be justified.. We aim to evaluate whether ticagrelor, a potent antiplatelet agent that blocks the P2Y12 receptor without requiring metabolic activation, reduces the risk of major vascular events compared with aspirin when randomization occurs within 24 h after symptom onset of a nonsevere ischemic stroke or high-risk transient ischemic attack.. Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) is a randomized, double-blind, event-driven trial and will include an estimated 13,600 participants randomized in 33 countries worldwide to collect 844 primary events.. The primary endpoint is the composite of stroke (ischemic or hemorrhagic), myocardial infarction, and death. Time to the first primary endpoint will be compared in the treatment groups during 90-day follow-up, with major hemorrhage serving as the primary safety endpoint. Participants will be followed for an additional 30 days after the randomized treatment period.. The SOCRATES trial fulfills an important clinical need by evaluating a potent antiplatelet agent as a superior alternative to current standard of care in patients presenting acutely with ischemic stroke or transient ischemic attack.

Topics: Adenosine; Aspirin; Double-Blind Method; Fibrinolytic Agents; Follow-Up Studies; Humans; Internationality; Ischemic Attack, Transient; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Research Design; Ticagrelor; Treatment Outcome

We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (e.g., cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events.. In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79-0.93; P=0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P=0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70-0.90; P<0.001) and a number needed to treat of 54. For cardiovascular death/myocardial infarction/stroke/(severe) recurrent ischemia/transient ischemic attack/arterial thrombotic events, total events were fewer with ticagrelor (2030 versus 2290; rate ratio, 0.88; 95% confidence interval, 0.82-0.95; P<0.001), with fewer recurrent events with ticagrelor (740 versus 834; P=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75-0.91; P<0.001). Recurrent PLATO major or Thrombolysis in Myocardial Infarction (TIMI) major non-coronary artery bypass graft bleeding events were infrequent and not different between the two therapies (P=0.96 and 0.38, respectively).. In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported.. URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Clopidogrel; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Severity of Illness Index; Stroke; Thrombosis; Ticagrelor; Ticlopidine; Treatment Outcome

Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages.. We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively).. Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.. URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Brain Ischemia; Clopidogrel; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Ticagrelor; Ticlopidine

The CHANCE-2 study compared 3 weeks of aspirin-ticagrelor to aspirin-clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin-ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown.. Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty.. Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY.. Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin-ticagrelor compared to standard-of-care aspirin-clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine.

Topics: Aspirin; Canada; Clopidogrel; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Quality of Life; Quality-Adjusted Life Years; Stroke; Ticagrelor; Ticlopidine

Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended on. Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively).. A total of 6,412. This post hoc analysis of CHANCE-2 trial showed that. This study provides Class II evidence that. URL: www.. gov. Unique identifier: NCT04078737.

Topics: Aspirin; Cerebral Infarction; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Neoplasm Recurrence, Local; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticagrelor; Treatment Outcome

It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II).. This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried. A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63-1.18];. In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials.. URL: https://www.. gov; Unique identifier: NCT04078737.

Topics: Aspirin; Atherosclerosis; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Wang Y, Meng X, Wang A, et al.

Topics: Alleles; Clopidogrel; Cytochrome P-450 CYP2C19; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

The goal of this work was to investigate the short-term time-course benefit and risk of ticagrelor with aspirin in acute mild-moderate ischemic stroke or high-risk TIA in The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial.. In an exploratory analysis of the THALES trial, we evaluated the cumulative incidence of irreversible efficacy and safety outcomes at different time points during the 30-day treatment period. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or nonhemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage and fatal bleedings. Net clinical impact was defined as the combination of these 2 endpoints.. This analysis included a total of 11,016 patients (5,523 in the ticagrelor-aspirin group, 5,493 in the aspirin group) with a mean age of 65 years, and 39% were women. The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction 1.15%, 95% CI 0.36%-1.94%) and remained throughout the 30-day treatment period. An increase in major hemorrhage was seen during the first week and remained relatively constant in the following weeks (absolute risk increase ≈0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (absolute risk reduction 0.97%, 95% CI, 0.17%-1.77%) and remained constant throughout the 30 days.. In patients with mild-moderate ischemic stroke or high-risk TIA, the treatment effect of ticagrelor-aspirin was present from the first week. The ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the treatment period, which may support the use of 30-day treatment with ticagrelor and aspirin in these patients.. This study provides Class II evidence that, for patients with mild-moderate ischemic stroke or high-risk TIA, the ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the 30-day treatment period.

Topics: Aged; Aspirin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemia; Ischemic Attack, Transient; Ischemic Stroke; Male; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Topics: Brain Ischemia; Humans; Ischemic Attack, Transient; Ischemic Stroke; Stroke; Ticagrelor

Major adverse cardiac event (MACE) and bleeding risks following percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are not well defined in individuals with heart failure (HF). We followed 1,145 individuals in the Pharmacogenomic Resource to improve Medication Effectiveness Genotype Guided Antiplatelet Therapy cohort for MACE and bleeding events following PCI for ACS. We constructed Cox proportional hazards models to compare MACE and bleeding in those with versus without HF, adjusting for sociodemographics, comorbidities, and medications. We also determined predictors of MACE and bleeding events in both groups. 370 (32%) individuals did and 775 (68%) did not have HF prior to PCI. Mean age was 61.7 ± 12.2 years, 31% were female, and 24% were African American. After a median follow-up of 0.78 years, individuals with HF had higher rates of MACE compared to those without HF (48 vs. 24 events per 100 person years) which remained significant after multivariable adjustment (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.00 to 1.72). Similarly, bleeding was higher in those with versus without HF (22 vs. 11 events per 100 person years), although this was no longer statistically significant after multivariable adjustment (HR 1.29, 95% CI 0.86 to 1.93). Diabetes and peripheral vascular disease were predictors of MACE, and end-stage renal disease was a predictor of bleeding among participants with HF. MACE risk is higher in individuals with versus without HF following PCI for ACS. However, the risk of bleeding, especially among those with end-stage renal disease , must be considered when determining post-PCI anticoagulant strategies.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Aspirin; Case-Control Studies; Clopidogrel; Diabetes Mellitus; Dual Anti-Platelet Therapy; Female; Heart Failure; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Ischemic Stroke; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Multivariate Analysis; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome

Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease.. Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality.. Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P=0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]).. Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.

Topics: Acute Coronary Syndrome; Aspirin; Cerebrovascular Disorders; Coronary Artery Disease; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Network Meta-Analysis; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticagrelor

Standard approaches to trial design and analyses can be inefficient and non-pragmatic. Failure to consider a range of outcomes impedes evidence-based interpretation and reduces power. Traditional approaches synthesizing information obtained from separate analysis of each outcome fail to incorporate associations between outcomes and recognize the cumulative nature of outcomes in individual patients, suffer from competing risk complexities during interpretation, and since efficacy and safety analyses are often conducted on different populations, generalizability is unclear. Pragmatic and efficient approaches to trial design and analyses are needed.. Approaches providing a pragmatic assessment of benefits and harms of interventions, summarizing outcomes experienced by patients, and providing sample size efficiencies are described. Ordinal outcomes recognize finer gradations of patient responses. Desirability of outcome ranking is an ordinal outcome combining benefits and harms within patients. Analysis of desirability of outcome ranking can be based on rank-based methodologies including the desirability of outcome ranking probability, the win ratio, and the proportion in favor of treatment. Partial credit analyses, involving grading the levels of the desirability of outcome ranking outcome similar to an academic test, provides an alternative approach. The methodologies are demonstrated using the acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes study (SOCRATES; NCT01994720), a randomized clinical trial.. Two 5-level ordinal outcomes were developed for SOCRATES. The first was based on a modified Rankin scale. The odds ratio is 0.86 (95% confidence interval = 0.75, 0.99;. Ordinal outcomes can improve efficiency through required pre-specification, careful construction, and analyses. Greater pragmatism can be obtained by composing outcomes within patients. Desirability of outcome ranking provides a global assessment of the benefits and harms that more closely reflect the experience of patients. The desirability of outcome ranking probability, the proportion in favor of treatment, the win ratio, and partial credit can more optimally inform patient treatment, enhance the understanding of the totality of intervention effects on patients, and potentially provide efficiencies over standard analyses. The methods provide the infrastructure for incorporating patient values and estimating personalized effects.

Topics: Adult; Aspirin; Humans; Ischemic Attack, Transient; Odds Ratio; Platelet Aggregation Inhibitors; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design; Stroke; Ticagrelor; Treatment Outcome

Topics: Aspirin; Brain Ischemia; Humans; Ischemic Attack, Transient; Stroke; Ticagrelor

Topics: Aspirin; Brain Ischemia; Humans; Ischemic Attack, Transient; Stroke; Ticagrelor

Johnston SC, Amarenco P, Denison H, et al.

Topics: Aspirin; Brain Ischemia; Humans; Ischemic Attack, Transient; Ischemic Stroke; Stroke; Ticagrelor

Stroke symptoms can be unsettling, even when symptoms resolve, but focusing on stroke prevention can be empowering provided that effective interventions for appropriate patient populations are available. Current options include interventions for symptomatic carotid artery stenosis, anticoagulation for atrial fibrillation, high-dose statins, new oral anticoagulants, new developments in atrial fibrillation detection, and new therapeutics are in development. For antiplatelet therapy, aspirin monotherapy is effective but dual antiplatelet therapy with the combination of aspirin and clopidogrel increases hemorrhage risks over the long term that outweigh potential benefits. In the short term though, both the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trials have shown a benefit of short-term dual-antiplatelet therapy, though the increased major hemorrhage risk seen in POINT could justify applying dual-antiplatelet therapy to just the first 21 days. Furthermore, since clopidogrel is a prodrug that must be metabolized to have antiplatelet activity, it is not surprising that the treatment effect in CHANCE was limited to patients who were not carriers of loss-of-function alleles for clopidogrel metabolism. Ticagrelor, an antiplatelet agent which failed to meet its primary endpoint as monotherapy compared to aspirin in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial, is currently being tested as combination therapy with aspirin compared to aspirin alone in Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES). These developments along with improvements to the infrastructure to perform rapid evaluations and to apply intensive secondary stroke prevention interventions hold continued promise for the future.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).. An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.. A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.. Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Topics: Adenosine; Aged; Aspirin; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Purinergic P2Y Receptor Antagonists; Risk; Stroke; Ticagrelor; Treatment Outcome

Topics: Adenosine; Aspirin; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Ticlopidine

Topics: Adenosine; Aspirin; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Ticlopidine

Topics: Aspirin; Double-Blind Method; Humans; Ischemic Attack, Transient; Stroke; Ticagrelor

Topics: Adenosine; Angioplasty, Balloon, Coronary; Aspirin; Drug Therapy, Combination; Evidence-Based Medicine; Guideline Adherence; Humans; Ischemic Attack, Transient; Long-Term Care; Platelet Aggregation Inhibitors; Postoperative Care; Stents; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Female; Humans; Ischemic Attack, Transient; Male; Stroke; Ticagrelor; Ticlopidine