ticagrelor and Brain-Ischemia

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

Optimal timing and strategy of antiplatelet monotherapy after dual-antiplatelet therapy (DAPT) consisting of aspirin and P2Y12 inhibitor for patients who underwent percutaneous coronary intervention (PCI) is still being debated. The aim of this study was to evaluate the effect of ticagrelor monotherapy after short-term DAPT after PCI on mortality.. A systematic review and meta-analysis was performed using PubMed to search for ticagrelor monotherapy after short-term DAPT comparing conventional DAPT in patients who underwent PCI. Three randomized trials encompassing 26 143 patients [ticagrelor monotherapy after 1-3 months of DAPT (n = 13 062) vs. conventional therapy (n = 13 081)] were included. The efficacy endpoint of all-cause mortality was significantly lower with the ticagrelor monotherapy group vs. the conventional therapy group [risk ratio (RR) = 0.80, 95% confidence interval (CI) 0.65-0.98; P = 0.03; I2 = 0%; number needed to treat for benefit (NNTB) = 320]. The safety endpoint of Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was also significantly lower with the ticagrelor monotherapy group vs. the conventional therapy group (RR = 0.67, 95% CI 0.49-0.92; P = 0.01; I2 = 65%; NNTB = 156). There were no significant differences in ischaemic stroke, acute myocardial infarction, and stent thrombosis. The favourable effects of the ticagrelor monotherapy vs. the conventional therapy on all-cause mortality and BARC type 3 or 5 bleeding were consistent in the subset of patients presenting acute coronary syndromes (n = 15 157).. Ticagrelor monotherapy after short-term DAPT of 1-3 months was associated with decreased all-cause mortality and BARC type 3 or 5 bleeding not offset by increase of cardiac death, ischaemic stroke, acute myocardial infarction, and stent thrombosis.

Topics: Brain Ischemia; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; 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

Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Ischemic Stroke; Stroke; Thrombolytic Therapy; Ticagrelor; Treatment Outcome

Platelets participate centrally in atherothrombosis, resulting in vessel occlusion and ischaemia. Consequently, optimisation of antiplatelet regimens has the potential to further reduce the residual burden of morbidity and mortality associated with atherosclerosis. Ticagrelor is a potent oral platelet P2Y

Topics: Aspirin; Brain Ischemia; Humans; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Thromboembolic complications are not uncommon in patients undergoing neurointerventional procedures. The use of flow diverting stents is associated with higher risks of these complications despite current dual antiplatelet regimens.. To explore contemporary evidence on the safety of emerging dual antiplatelet regimens in flow diverting stenting procedures.. We performed a systematic review and meta-analysis to identify relevant articles in electronic databases, and relevant references. Studies reporting the complications and mortality of flow diverting stenting procedures using acetyl salicylic acid (ASA) + ticagrelor or ASA + prasugrel compared with ASA + clopidogrel were included.. Of 452 potentially relevant studies, we identified 49 studies (2526 patients) which reported the safety of ticagrelor or prasugrel for pooled analysis, and five studies (1005 patients) for meta-analysis. The pooled overall mortality in all studies was 2.14%, ischemic complications 6.89%, and hemorrhagic complications 3.68%. The use of ticagrelor or prasugrel was associated with a lower risk of mortality compared with clopidogrel (RR=4.57, 95% CI 1.23 to 16.99; p=0.02). Considering ischemic events, ASA + clopidogrel was as safe as ASA + prasugrel (RR=0.55, 95% CI 0.11 to 2.74; p=0.47) and ASA + ticagrelor (RR=0.74, 95% CI 0.32 to 1.74; p=0.49). ASA +ticagrelor was not associated with a higher risk of hemorrhagic complications (RR=0.92, 95% CI 0.27 to 3.16; p=0.89).. Evidence suggests that dual antiplatelet regimens including ticagrelor or prasugrel are safe for patients undergoing flow diversion procedures. Regimens using ticagrelor were associated with better survival than those using clopidogrel in the included studies.

Topics: Aspirin; Brain Ischemia; Clopidogrel; Female; Humans; Male; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Self Expandable Metallic Stents; Ticagrelor; Treatment Outcome

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

Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke.. Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses.. Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts.. Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Clopidogrel; Disease-Free Survival; Female; Humans; Male; Myocardial Infarction; Registries; Risk Factors; Stroke; Survival Rate; Ticagrelor

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

SARS-CoV-2 (COVID-19) infection is associated with acute ischemic stroke (AIS), which may be due to a prothrombotic state. Early reports have suggested high rates of reocclusion following mechanical thrombectomy (MT) with poor radiographic and clinical outcomes. We report our early experience using intra-procedural antithrombotics to address SARS-CoV-2 reocclusion.. We identified 6 patients that experienced early reocclusion after MT for COVID-19-associated AIS through retrospective chart review abstracting their basic demographics, COVID-19 status, and stroke management. All these patients were treated after reocclusion with aspirin and cangrelor intra-procedurally, the latter of which was converted to ticagrelor post-procedurally. Some patients additionally received argatroban infusion intraprocedurally.. Mean age was 54. There were 3 post-procedural and 3 intra-procedural re-occlusions. After repeat thrombectomy and treatment with aspirin and cangrelor, those with post-procedure reocclusion did not show further reocclusion, while those with intra-procedural reocclusion showed radiographic improvement with intraprocedural cangrelor administration. Outcomes for these patients were poor, with a median mRS of 4. Two patients developed petechial hemorrhage of their stroke which was managed conservatively, and one developed a retroperitoneal hemorrhage from femoral access requiring transfusion. There were no patients who developed new parenchymal hematomas.. COVID-19 AIS may be associated with a hypercoagulable state which risks malignant reocclusion complicating MT. We found antithrombotic treatment periprocedural cangrelor with or without argatroban transitioned to oral aspirin with ticagrelor to be a viable method for management of these patients.

Topics: Aspirin; Brain Ischemia; COVID-19; Humans; Ischemic Stroke; Middle Aged; Retrospective Studies; SARS-CoV-2; Stroke; Thrombectomy; Ticagrelor; Treatment Outcome

Stroke after acute coronary syndrome (ACS) can be devastating. It is uncertain whether the risks of ischaemic stroke or intracranial haemorrhage (ICH) are associated with different choices of P2Y12 inhibitors (potent P2Y12 inhibitors such as ticagrelor and prasugrel vs clopidogrel). Even though East Asians are known to have different thrombotic and haemorrhagic profiles from Caucasians, data on Chinese patients are sparse.. This was a retrospective cohort study conducting in Chinese patients with ACS who underwent first-ever percutaneous coronary intervention from 14 hospitals in Hong Kong between 2010 and 2017. The primary efficacy endpoint was ischaemic stroke. The secondary efficacy endpoint was a composite outcome of thrombotic events including all-cause mortality, non-fatal myocardial infarction and ischaemic stroke. The primary safety endpoint was ICH. The secondary safety endpoint was a composite of major bleeding events.. After adjustment of baseline characteristics by 1:1 propensity score matching, a total of 6220 patients (3110 on each group) were analysed. Compared with clopidogrel, potent P2Y12 inhibitors were associated with a lower risk of ischaemic stroke (HR 0.57; 95% CI 0.37 to 0.87; p=0.008) and a lower risk of thrombotic events (HR 0.77; 95% CI 0.66 to 0.90; p=0.001). Potent P2Y12 inhibitor was associated with similar risk of ICH (HR 0.65; 95% CI 0.34 to 1.25, p=0.20) and major bleeding (HR 0.83; 95% CI 0.68 to 1.01, p=0.069).. Potent P2Y12 inhibitors were associated with a lower adjusted risk of ischaemic stroke and thrombotic events, compared with clopidogrel. The risks of ICH and major bleeding were similar.

Topics: Acute Coronary Syndrome; Brain Ischemia; China; Clopidogrel; Hemorrhage; Hemorrhagic Stroke; Humans; Intracranial Hemorrhages; Ischemic Stroke; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Stroke; Ticagrelor

Insulin resistance was reported to increase the risk of ischemic stroke, which can be assessed by the triglyceride glucose (TyG) index. However, it remains unclear whether the TyG index influences the platelet reactivity during the treatment of ischemic patients.. Ischemic stroke patients receiving dual antiplatelet therapy (DAPT) within 48 h onset were consecutively included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The top quartile of TyG index was defined as insulin resistance. The platelet reactivity was assessed by thromboelastography. The platelet inhibition rate induced by arachidonic acid (AA) or adenosine diphosphate (ADP) was used to confirm the high residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel, respectively. The association between TyG index and platelet reactivity was assessed by Kruskal-Wallis test. The independent risk factors of HRPR were determined by multivariate logistic regression analysis.. A total of 1002 patients were included and divided into 4 groups by quartiles of the TyG index (< 2.02; 2.02-2.27; 2.27-2.52; ≥2.52). The findings demonstrated that the maximum intensity of the clot increased, but the AA-induced platelet inhibition rate decreased, depending on the TyG index quartiles. No significant difference was found in the ADP-induced platelet inhibition rate among groups. The prevalence of aspirin HRPR increased depending on the TyG index quartile. Unlike the non-insulin resistance group, the insulin resistance group was independently associated with aspirin HRPR (OR = 1.689, 95% CI 1.14 to 2.51, P = 0.009).. In acute ischemic stroke patients taking DAPT, the elevation of the TyG index is associated with enhanced platelet reactivity and higher prevalence of aspirin HRPR. Insulin resistance assessed by the TyG index could be an independent risk factor for aspirin HRPR.

Topics: Brain Ischemia; Glucose; Humans; Ischemic Stroke; Platelet Aggregation; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticagrelor; Ticlopidine; Triglycerides

Ticagrelor plus aspirin could reduce the risks of major adverse cardiac events in diabetic patients with stable coronary artery disease (SCD), and yet it also increases bleeding risk. This study would compare the cost and effectiveness of aspirin and ticagrelor plus aspirin therapies in diabetic patients with SCD from a US healthcare sector perspective.. A state-transition Markov model was developed to project probabilities of myocardial infarction, ischaemic stroke, bleeding, and death with and without ticagrelor among all diabetic patients with SCD as the overall population, and those with a history of previous percutaneous coronary intervention (PCI) as a sub-population. Model inputs were extracted from published sources. Lifetime costs and quality-adjusted life-years (QALYs) were measured. The clinical benefits and bleeding risk of ticagrelor added to aspirin were translated into additional 0.08 QALYs at incremental costs of $19 580 in the overall population, yielding an incremental cost-utility ratio (ICUR) of $260 032/QALY. In the sub-population with an additional 0.43 QALYs at an incremental cost of $20 189, the ICUR was $46 426/QALY. Two-way sensitivity showed the clinical benefits of ticagrelor plus aspirin was counterbalanced by its risk of major bleeding. One-way sensitivity and probabilistic sensitivity analysis demonstrated that the results were generally robust except the all-cause death reduction.. The results indicated that ticagrelor plus aspirin is likely to be a cost-effective option in the diabetic patients with a history of PCI. Diabetes management can be improved by carefully prescribing ticagrelor to individuals with low risk of bleeding and high risk of ischaemic events.

Topics: Aspirin; Brain Ischemia; Coronary Artery Disease; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

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

Increasing studies showed that several anti-platelet drugs turned out to be a promising strategy for inflammatory response. In this study, we investigated the protective efficiency of pretreatment of indobufen or aspirin combined with clopidogrel or ticagrelor (IACT) on cerebral ischemic injury via NF-κB/NLRP3 pathway. Ischemia/reperfusion (I/R) injury was simulated in vivo by middle cerebral artery occlusion/reperfusion (MCAO/R) model, and rats were pretreated with indobufen and aspirin and their combinations with clopidogrel or ticagrelor respectively. The platelet aggregation, cerebral infarct size, water content, neurological impairment and LDH release were measured. The relative expression of inflammasome mediated pyroptosis was determined by ELISA, RT-PCR, Tunel, Immunofluorescence and Western blotting as appropriate. In vitro, I/R injury was simulated in PC12 cells using oxygen glucose deprivation/reperfusion (OGD/R) and Lipopolysaccharide (LPS) to induce pyroptosis. The effect of combinations were significantly greater than MCAO/R group on decreasing the platelet aggregation, infarct size, brain edema, LDH release and neurologic impairment. LPS aggravated I/R-induced PC12 cell injury, which was significantly suppressed by pretreatment of IACT and Bay11-7082. Mechanistically, IACT alleviated transcriptionally encoded IL-1β, IL-18 and NLRP3 via inhibiting nuclear transportation of NF-κB. Importantly, at protein level, NLRP3, Caspase-1, IL-18, IL-1β and GSDMD were significantly decreased in combination groups both in vivo and vitro. IACT reduce inflammasome mediated pyroptosis in MCAO/R rats and OGD/R PC12 cells through inhibiting NF-κB/NLRP3 signaling pathway, which suggests that drug combination is a protective strategy with clinical potential against I/R-induced injury. Graphical abstract.

Topics: Animals; Aspirin; Brain Ischemia; Clopidogrel; Inflammasomes; Ischemic Stroke; Isoindoles; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Phenylbutyrates; Pyroptosis; Rats; Reperfusion Injury; Stroke; Ticagrelor

Patients with ischemic stroke are often treated with clopidogrel monotherapy as part of secondary stroke prevention. The prevalence of loss of function (LOF) mutations in the CYP2C19 gene is higher in Asians than in Western populations. Patients with loss of function (LOF) mutations are at risk for poorer secondary outcomes when prescribed clopidogrel.. We aimed to determine the cost effectiveness of genotype-guided antiplatelet therapy in an Asian population with the aim of prescribing ticagrelor as an alternative to patients with LOF mutations.. Markov models were developed to look at the cost effectiveness of genetic testing of CYP2C19, with patients who screened positive for LOF alleles being switched to ticagrelor compared to universal clopidogrel treatment. Effect ratios were obtained from the literature and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. Lifetime costs and quality-adjusted life-years (QALYs) were calculated. The primary endpoints were the incremental cost-effectiveness ratios (ICERs).. The prevalence of the LOF mutations was 61% in the population, with 65% of ethnic Chinese, 60% of ethnic Indian, and 53% of ethnic Malay patients having LOF mutations. Based on this prevalence, the overall ICER of genetic testing was S$33,839/QALY with ICERS of S$30,755/QALY, S$33,177/QALY, and S$41,470/QALY for Chinese, Indians, and Malays, respectively.. This study suggests that it is cost effective to screen for LOF mutations in the CYP2C19 gene in ischemic stroke populations, with ticagrelor as a substitute for clopidogrel in those with LOF mutations.

Topics: Aged; Asian People; Brain Ischemia; Clopidogrel; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Genotype; Humans; Ischemic Stroke; Loss of Function Mutation; Middle Aged; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Ticagrelor

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

To evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI).. Data for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n = 23,447) were treated with clopidogrel, while those in the later cohort (n = 24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke.. Of 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p = 0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke.. The introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

Topics: Aged; Brain Ischemia; Clopidogrel; Comorbidity; Humans; Incidence; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Stroke; Sweden; Ticagrelor; Time Factors; Treatment Outcome

Aims It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population. Methods and results Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period ( p = 0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p = 0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction. Conclusion The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

Topics: Aged; Brain Ischemia; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Prognosis; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Sweden; Ticagrelor; Time Factors

Topics: Acute Coronary Syndrome; Brain Ischemia; Humans; Incidence; Purinergic P2Y Receptor Antagonists; Registries; Sweden; Ticagrelor

Ticagrelor is a direct acting and reversibly binding P2Y12 antagonist approved for the prevention of thromboembolic events. Its potential benefits in ischemic stroke have not been investigated sufficiently. Mice were subjected to 2 hours of transient middle cerebral artery occlusion (MCAO). Mice were orally treated with ticagrelor (10 or 30 mg/kg), aspirin (60 mg/kg), or vehicle at 3 and 24 hours before MCAO and 0 and 6 hours after reperfusion. The infarct volume and neurological deficits 22 hours after reperfusion were evaluated. Cerebral blood flow (CBF) within 24 hours after MCAO was monitored. We performed western blotting and in vitro analysis using oxygen-glucose deprivation (OGD) stress in human brain microvessel endothelial cells (HBMVECs) to investigate the protective effects of ticagrelor. Ticagrelor (30 mg/kg) improved neurological deficits, reduced the infarct volume, and improved CBF. It promoted the phosphorylation of endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase 1/2 (ERK1/2) during the early phase after reperfusion. Increased phosphorylation of eNOS and ERK1/2 were also observed in HBMVECs after OGD stress. Ticagrelor attenuate ischemia reperfusion injury possibly via phosphorylation of eNOS and ERK1/2 in endothelial cells. This suggests that ticagrelor has neuroprotective effects via mechanisms other than its antiplatelet action.

Topics: Animals; Brain Infarction; Brain Ischemia; Cerebrovascular Circulation; Disease Models, Animal; Humans; Infarction, Middle Cerebral Artery; Mice; Neuroprotective Agents; Nitric Oxide Synthase Type III; Phosphorylation; Purinergic P2Y Receptor Antagonists; Reperfusion Injury; Stroke; Ticagrelor

Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI.. We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year.. We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE.. HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i.

Topics: Acute Disease; Adenosine; Aspirin; Blood Platelets; Brain Ischemia; Cardiovascular Diseases; Clopidogrel; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Survival Analysis; Ticagrelor; Ticlopidine

The ADP-responsive P2Y12 receptor is expressed on both platelets and microglia. Clinical data show that ticagrelor, a direct-acting, reversibly binding P2Y12-receptor antagonist, reduces total cardiovascular events, including stroke. In our present study, we investigated the expression of P2Y12 receptors and the effects of ticagrelor on brain injury in Sprague-Dawley rats subjected to a permanent middle cerebral artery occlusion (MCAo). Rats were treated per os with ticagrelor 3 mg/kg or vehicle at 10 minutes, 22, and 36 hours after MCAo and killed after 48 hours. Immunofluorescence analysis showed an ischemia-related modulation of the P2Y12 receptor, which is constitutively expressed in Iba1(+) resting microglia. After MCAo, activated microglia was mainly concentrated around the lesion, with fewer cells present inside the ischemic core. Ticagrelor significantly attenuated the evolution of ischemic damage-evaluated by magnetic resonance imaging (MRI) at 2, 24, and 48 hours after MCAo-, the number of infiltrating cells expressing the microglia/monocyte marker ED-1, the cerebral expression of proinflammatory mediators (interleukin 1 (IL-1), monocyte chemoattractant protein 1 (MCP-1), nitric oxide synthase (iNOS)) and the associated neurologic impairment. In transgenic fluorescent reporter CX3CR1-green fluorescent protein (GFP) mice, 72 hours after MCAo, ticagrelor markedly reduced GFP(+) microglia and both early and late infiltrating blood-borne cells. Finally, in primary cultured microglia, ticagrelor fully inhibited ADP-induced chemotaxis (P<0.01). Our results show that ticagrelor is protective against ischemia-induced cerebral injury and this effect is mediated, at least partly, by inhibition of P2Y12-mediated microglia activation and chemotaxis.

Topics: Adenosine; Animals; Brain Ischemia; Chemokine CCL2; Ectodysplasins; Fibrinolytic Agents; Interleukin-1; Mice; Mice, Transgenic; Microglia; Nerve Tissue Proteins; Nitric Oxide Synthase Type II; Purinergic P2Y Receptor Antagonists; Rats; Rats, Sprague-Dawley; Stroke; Ticagrelor; Time Factors