Incidence Of Ischemic Events Research Articles

Efficacy and Safety of Ticagrelor Monotherapy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Retrospective Study

Background: Dual antiplatelet therapy (DAPT) is the standard treatment for percutaneous coronary intervention (PCI), but its optimal duration is controversial. Ticagrelor monotherapy has obvious advantages in reducing the bleeding risk, so this study investigated its efficacy and safety. Objective: The objective of this study was to explore the efficacy and safety of administering ticagrelor monotherapy to patients with acute coronary syndrome (ACS) undergoing PCI. Methods: This retrospective study chose 110 patients with ACS undergoing PCI from January 2022 to April 2024. In accordance with different antiplatelet therapy methods, 58 patients received DAPT of ticagrelor and aspirin, and 54 cases were included in the control group (CG) after excluding 4 cases. Meanwhile, 52 cases received ticagrelor monotherapy after 3 months of DAPT, and 49 cases were classified as the observation group (OG) after excluding 3 cases. The platelet inhibition rates, platelet aggregation functions, and adverse events before and after treatment were compared. Results: Intergroup comparison showed no significant difference in adenosine diphosphate-induced platelet inhibition rates 3 months (T1) and 6 months (T2) after operation (p = 0.129, 0.137), and the inhibition rate in OG was significantly lower than that in CG 12 months (T3) after operation (p < 0.001). At T1, T2, and T3, no significant difference in fibrinogen and prothrombin time was found (p = 0.112, 0.751, 0.590, 0.771, 0.109, 0.121). After 12-month follow-up, intergroup comparison revealed no significant difference in the incidence of ischemic events (OG vs. CG: 4.08% vs. 9.26%; p = 0.515) and a significantly lower incidence of bleeding events in OG than in CG (OG vs. CG: 4.08% vs. 18.52%; p = 0.023). Conclusion: Administering ticagrelor monotherapy after short-term DAPT (three months) to patients with ACS undergoing PCI effectively controlled the platelet inhibition rate, reduced bleeding events, and did not increase the risk of ischemic events.

Is initial unilateral revascularization acceptable in pediatric patients with bilateral moyamoya disease with mild contralateral hemodynamic disturbance?

Although asymmetrical vascular involvement between hemispheres is common in pediatric patients with bilateral moyamoya disease, whether hemispheres with mild vascular changes and hemodynamic impairment require immediate surgical revascularization or whether they can be observed until disease progression remains unclear. The authors evaluated the long-term outcomes of their strategy to initially perform unilateral surgery and withhold surgery to the contralateral hemispheres with mild vascular changes and hemodynamic impairment. The authors retrospectively evaluated Japanese pediatric patients (onset age ≤ 15 years) diagnosed with bilateral sporadic moyamoya disease who underwent unilateral revascularization. The authors investigated whether the patient underwent additional collateral surgery and the incidence of ischemic events during follow-up. They also compared visual assessments of arterial spin labeling (ASL) images obtained before initial surgery, before additional contralateral surgery, and at last follow-up. Overall, 30/47 patients (63.8%) experienced progression of hemodynamic impairment in the contralateral hemisphere and underwent additional surgery. The age at initial surgery of the patients who needed additional contralateral surgery was significantly younger than that of the patients who did not require contralateral surgery (mean [SD] 7.0 [3.0] years vs 9.8 [2.6] years, p = 0.002). One patient (age 4 years) developed ischemic stroke before admission for preoperative evaluation 2 months after novel symptom onset, and another patient (age 6 years) experienced ischemic stroke in the contralateral hemisphere while discontinuing antiplatelet agents before surgery; both patients fully recovered from the neurological deficits. In contralateral hemispheres that required additional surgery, the ASL visual assessment scores significantly decreased before the additional contralateral surgery compared to those obtained before the initial surgery (p = 0.008). In pediatric patients with bilateral moyamoya disease, withholding surgery for hemispheres with mild vascular changes and hemodynamic impairment is generally safe. Younger patients were more likely to experience contralateral progression and require additional surgery, so close follow-up is needed. ASL imaging is useful for detecting and following the progression of hemodynamic impairment in conservatively treated hemispheres.

Cardiovascular events in CML patients treated with Nilotinib: validation of the HFA-ICOS baseline risk score

BackgroundThe therapeutic landscape of chronic myeloid leukaemia (CML) has been transformed by tyrosine kinase inhibitors (TKI). Nilotinib, showed higher rates of major molecular response than imatinib, however associated with higher cardiovascular (CV) toxicity. We sought to describe the CV events associated with nilotinib in a real-world population and assess the predictive value of the HFA-ICOS risk score.MethodsThe HFA-ICOS baseline risk was calculated for patients with CML treated with nilotinib beween 2006 and 2021. The primary end point was the incidence of all CV events. The secondary end point was the incidence of ischaemic events. Survival analysis evaluated the risk (hazard ratio [HR]) of events stratified by baseline risk category, whilst on nilotinib therapy.ResultsTwo hundred and twenty-nine eligible patients were included. The incidence of CV events was 20.9% (95% CI: 15.7–26.2%) following a median duration of treatment of 34.4 months. The secondary end point occurred in 12.7% (95% CI: 8.4–16.9%) of the population. Patients with higher HFA-ICOS baseline score had higher rates of CV events (low: 11.2%, medium: 28.2% [HR: 2.51, 95% CI: 1.17–5.66], high/very high: 32.4% [HR: 3.57, 95% CI: 1.77–7.20]) and ischaemic events (low: 5.20%, medium: 17.9% [HR: 2.19, 95% CI: 0.97–4.96], high/very high: 21.6% [HR: 3.9, 95% CI: 1.91–7.89]). In patients who did not have a CV event, the median total dose at last follow up or cessation of nilotinib therapy was lower when compared to the total daily median dose of nilotinib in patients who had a CV event (450 mg vs. 600 mg, p = 0.0074).ConclusionsThe HFA-ICOS risk stratification tool is an efficient discriminator at low, medium and high/very high risk of developing cardiovascular events, with an overall positive trend towards increasing cardiotoxicity rates with rising risk catergories. This study provides evidence to support the use of this predictive tool in nilotinib treated patients.

Efficacy of P2Y12 receptor inhibitors in myocardial infarction in individuals carrying different CYP2C19 genotypes living in the northern region of Russia

Aim. To evaluate the efficacy of P2Y12 receptor inhibitors (clopidogrel and ticagrelor) in patients with myocardial infarction (MI) living in the northern region of Russia (Khanty-Mansi Autonomous Okrug — Yugra), depending on the carriage of various CYP2C19 allelic variants.Material and methods. This prospective observational study included 218 patients with acute MI who underwent percutaneous coronary intervention (PCI). The patients also underwent determination of allelic variants of the CYP2C19 gene. Patient were divided into groups receiving clopidogrel (n=164, 75%) and ticagrelor (n=54, 25%). Using biostatistical analysis methods, a comparison of clinical and genetic characteristics was performed, as well as an assessment of the risk of ischemic events between the groups in the long-term (108 months, 9 years) post-infarction period.Results. Reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes, as well as severe comorbidity, are reliable independent predictors of composite outcome (cardiovascular death, recurrent acute coronary syndrome, coronary stent/bypass thrombosis, myocardial revascularization, acute ischemic cerebrovascular accident) during a long-term (9 years) follow-up. The advantages of ticagrelor over clopidogrel in terms of the effect on the incidence of ischemic events in the long-term period were established without a significant difference for bleeding both in the general cohort of patients and among carriers of CYP2C19 allelic variants (*1/*2, *2/*2, *1/*3) and (*1/*17,*17/*17) in patients with MI.Conclusion. Ticagrelor is significantly more effective than clopidogrel in reducing the risk of ischemic events in the general cohort of patients, as well as in carriers of reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes during 9-year follow-up after the index MI.

Is CYP2C Haplotype Relevant for Efficacy and Bleeding Risk in Clopidogrel-Treated Patients?

A recently discovered haplotype-CYP2C:TG-determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, RM; or ultrarapid, UM). We investigated whether the CYP2C:TG haplotype affected efficacy/bleeding risk in clopidogrel-treated patients. Adults (n = 283) treated with clopidogrel over 3-6 months were classified by CYP2C19 phenotype based on the CYP2C19*2*17 genotype, and based on the CYP2C19/CYP2C cluster genotype, and regarding carriage of the CYP2:TG haplotype, and were balanced on a number of covariates across the levels of phenotypes/haplotype carriage. Overall, 45 (15.9%) patients experienced ischemic events, and 49 (17.3%) experienced bleedings. By either classification, the incidence of ischemic events was similarly numerically higher in PM/IM patients (21.6%, 21.8%, respectively) than in mutually similar NM, RM, and UM patients (13.2-14.8%), whereas the incidence of bleeding events was numerically lower (13.1% vs. 16.6-20.5%). The incidence of ischemic events was similar in CYP2C:TG carries and non-carries (14.1% vs. 16.1%), whereas the incidence of bleedings appeared mildly lower in the former (14.9% vs. 20.1%). We observed no signal to suggest a major effect of the CYP2C19/CYP2C cluster genotype or CYP2C:TG haplotype on the clinical efficacy/safety of clopidogrel.

One-year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after acute large vessel occlusion stroke

Although low-dose direct oral anticoagulants (DOACs) are recommended for patients at high risk of bleeding complications, it remains unclear whether the dose reduction in real-world setting is also appropriate in patients after large-vessel occlusion (LVO) stroke. This study hypothesized that patients with atrial fibrillation (AF) and LVO receiving low-dose DOACs have an increased risk of ischemic and hemorrhagic events. The study aimed to assess 1 year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after LVO stroke. A post hoc analysis was performed using the acute LVO registry data, which enrolled patients with AF and LVO who received apixaban within 14 days of stroke onset. The incidences of ischemic events (ischemic stroke, acute coronary syndrome, acute myocardial infarction, and systemic embolism), major bleeding events, and death from any cause were compared between patients receiving standard- and low-dose apixaban. Of 643 patients diagnosed with LVO, 307 (47.7%) received low-dose apixaban. After adjustment for clinically relevant variables, no significant differences were observed in the incidence of ischemic events (adjusted hazard ratio [aHR]: 2.12, 95% confidence interval [CI] 0.75–6.02), major bleeding events (aHR: 1.17, 95% CI 0.50–2.73), and death from any cause (aHR: 1.95, 95% CI 0.78–4.89) between patients receiving standard- and low-dose apixaban. No significant differences were observed in the incidence of ischemic events, major bleeding events, or death from any cause between patients with AF and LVO receiving standard- and low-dose apixaban.

Impact of CYP2C19 gene polymorphisms on clinical outcomes in patients with myocardial infarction during 60 months of follow-up

Objective: To evaluate the effect of CYP2C19 gene polymorphisms on clinical outcomes in patients after successful revascularization for acute myocardial infarction with and without ST segment elevation during clopidogrel therapy for 60 months of follow-up.Methods: From 2011 to 2012, 363 patients with acute myocardial infarction who underwent coronary revascularization were included in the study. In the postoperative period, the patients underwent genetic analysis for the CYP2C19 gene polymorphism. All patients received dual antiplatelet therapy with aspirin and clopidogrel. The 60-month follow-up period assessed the primary composite endpoint of the cumulative incidence of all-cause mortality, recurrent myocardial infarction, and stroke.Results: At 60 months after the initial intervention, 71 patients had a composite primary endpoint event (all-cause death, recurrent myocardial infarction, or stroke): 50 (20%, 95% CI 16–25) in the group patients with "wild genotype" and 21 patients of the "loss of function (LOF) *2+*3" group (19%, 95% CI 13–27). No significant relationship was observe between carriage of LOF alleles of the CYP2C19 and the primary endpoint during the 60-month follow-up (HR 0.99, 95% CI 0.59–1.65, P = .965), as well as between carriage of the homozygous CYP2C19 variant (*2/*2) and the development of myocardial infarction during the same period (HR 1.26, 95% CI 0.30–5.20, P = .752).Conclusion: No correlation was observed between the CYP2C19 gene polymorphisms (*2, *3 alleles) and the incidence of ischemic events in patients with myocardial infarction after myocardial revascularization throughout a 60-month follow-up period. Received 27 November 2022. Revised 25 September 2023. Accepted 26 September 2023. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: I.O. GrazhdankinData collection and analysis: I.O. GrazhdankinStatistical analysis: V.L. LukinovDrafting the article: I.O. Grazhdankin, A.A. Prokhorikhin, V.I. Baystrukov, E.I. Kretov, V.L. LukinovCritical revision of the article: A.M. ChernyavskiyFinal approval of the version to be published: I.O. Grazhdankin, A.A. Prokhorikhin, V.I. Baystrukov, E.I. Kretov, A.M. Chernyavskiy, V.L. Lukinov

Activated clotting time and outcomes of chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-CTO Registry.

The optimal range of activated clotting time (ACT) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We examined the association between ACT and in-hospital ischemic and bleeding outcomes in patients who underwent CTO PCI in the Prospective Global Registry for the Study of CTO Intervention. ACT values were available for 4377 patients who underwent CTO PCI between 2012 and 2023 at 29 centers. The mean ACT distribution was less than 250 seconds (19%), 250 to 349 seconds (50%), and greater than or equal to 350 seconds (31%). The incidence of ischemic events, bleeding events, and net adverse cardiovascular events (NACE) was 0.8%, 3.0%, and 3.8%, respectively. In multiple logistic regression analysis, increasing nadir ACT was associated with decreasing ischemic events (adjusted odds ratio [aOR] per 50-second increments: 0.69 [95% confidence interval (CI), 0.50-0.94; P=.017]; and increasing peak ACT was associated with increasing bleeding events (aOR per 50-second increments: 1.17 [95% CI ,1.01-1.36; P=.032]). A U-shaped association was seen between mean ACT and NACE, where restricted cubic spline analysis demonstrated that patients with a low ( less than 200 seconds) or high ( greater than 400 seconds) ACT had increasing NACE risk compared with an ACT of 200 to 400 seconds (aOR 2.06, 95% CI 1.18-3.62; P=.012). Among patients who underwent CTO PCI, mean ACT had a U-shaped relationship with NACE, where patients with a low ( less than 200 seconds) ACT (driven by ischemic events) or high ( greater than 400 seconds) ACT (driven by bleeding) had higher NACE compared with an ACT of 200 to 400 seconds.

Abstract 12054: Activated Clotting Time and Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry

Introduction: The optimal range of activated clotting time (ACT) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods: We examined the association between ACT and in-hospital ischemic and bleeding outcomes in patients who underwent CTO PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436). Results: ACT values were available for 4,377 patients who underwent CTO PCI between 2012 and 2023 at 29 centers. Mean ACT distribution was: <250 seconds (19%), 250-349 seconds (50%), and ≥350 seconds (31%). The incidence of ischemic events was 0.8%, bleeding events 3.0%, and net adverse cardiovascular events (NACE, composite of in-hospital all-cause mortality, myocardial infarction, stroke, urgent repeat revascularization, pericardiocentesis, and bleeding) 3.8%. In multiple logistic regression analysis, increasing nadir ACT was associated with decreasing ischemic events: adjusted odds ratio (aOR) per 50-second increments: 0.69 (95% confidence interval [CI] 0.50-0.94, p=0.017); and increasing peak ACT was associated with increasing bleeding events: aOR per 50-second increments 1.17 (95% CI 1.01-1.36, p=0.032). A U-shaped association was seen between mean ACT and NACE, where restricted cubic spline analysis demonstrated that patients with low (<200 seconds) or high (>400 seconds) ACT had increasing NACE risk, compared with ACT 200-400 seconds (aOR 2.06, 95% CI 1.18-3.62, p=0.012) (Figure). Conclusions: Among patients who underwent CTO PCI, mean ACT had a U-shaped relationship with NACE, where patients with low (<200 seconds) ACT (driven by ischemic events) or high (>400 seconds) ACT (driven by bleeding) had higher NACE compared with ACT of 200-400 seconds.

Effect of dual antiplatelet therapy prolongation in acute coronary syndrome patients with both high ischemic and bleeding risk: insight from the OPT-CAD study.

In current clinical practice, controversy remains regarding the clinical benefits of prolonged dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients facing high risks of both ischemia and bleeding ("bi-risk") following percutaneous coronary intervention (PCI). This study aimed to investigate the feasibility of identifying a group of bi-risk ACS patients after PCI using the OPT-BIRISK criteria, emphasizing extended DAPT treatment safety and efficacy beyond 12 months in these bi-risk ACS after PCI in real-world conditions. This analysis compared extended DAPT and single antiplatelet therapy (SAPT) at 12-24 months in ACS patients undergoing PCI complicated with both ischemic and bleeding risk as defined by OPT-BIRISK criteria without premature DAPT discontinuation before 9 months or major clinical adverse events within 12 months. This was a post hoc analysis of the Optimal antiPlatelet Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) study. The main research outcome was the incidence of ischemic events within 12-24 months, which was determined as a composite of stroke, myocardial infarction, and cardiac death events. Through propensity score matching (PSM), groups were balanced. For the external validation of the OPT-BIRISK criteria to identify a bi-risk ACS patient, ischemic events, BARC 2, 3, 5 bleeding events, and BARC 3, 5 bleeding events at 5 years were analyzed. The total number of ACS patients analyzed in this analysis was 7,049, of whom 4,146 (58.8%) were bi-risk patients and 2,903 (41.2%) were not. The frequency of ischemic events was significantly different between the two groups at 5 years (11.70% vs. 5.55%, P < 0.001), and the incidence of BARC 2,3,5 bleeding was significantly higher in the bi-risk group (6.90% vs. 4.03%, P < 0.001) than in the non-bi-risk group. Among the bi-risk patients without any clinical adverse events within 12 months that underwent extended DAPT treatment (n = 2,374, 75.7%) exhibited a lower risk of stroke at 12-24 months (1.10% vs. 2.10%, P = 0.036) relative to those that underwent SAPT (n = 763, 24.3%), while bleeding risk did not differ significantly between these groups. PSM cohort analysis results were consistent with those of overall group analyses. In conclusion, the findings showed that using the OPT-BIRISK criteria could help physicians identify ACS patients at a high risk of developing recurrent ischemia and bleeding episodes after PCI. Compared to antiplatelet monotherapy, a strategy of extended DAPT may offer potential benefits in lowering the risk of stroke without carrying a disproportionately high risk of serious bleeding problems among these patients who were event-free after a year of DAPT.

Contemporary Use of Ticagrelor vs Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A GRACE Risk Score Stratification–Based Analysis in a Large-Scale, Real-World Study From China

ObjectiveTo evaluate potential gains in outcomes from ticagrelor-based strategy according to risk stratification by Global Registry of Acute Coronary Events (GRACE) score. MethodsA total of 19,704 patients discharged alive post–acute coronary syndrome who underwent percutaneous coronary intervention and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, composed of cardiac death, myocardial infarction, and/or stroke. Secondary outcomes included all-cause mortality and Bleeding Academic Research Consortium type 2 to 5 and 3 to 5 bleeding. ResultsThe ticagrelor group comprised 6432 (32.6%) patients and the clopidogrel group comprised 13,272 (67.4%) patients. During the follow-up period, there was a significant reduction in the incidence of ischemic events in patients treated using ticagrelor who had excessive risk of bleeding. According to the GRACE score, among low-risk patients, ticagrelor use compared with clopidogrel was not associated with decreased ischemic events (HR, 0.82; 95% CI, 0.57 to 1.17; P=.27) with excessive risk of Bleeding Academic Research Consortium type 3 to 5 bleeding (HR, 1.59; 95% CI, 1.16 to 2.17; P=.004). The risk of ischemic events (HR, 0.60; 95% CI, 0.41 to 0.89; P=.01) were lower in the intermediate- to high-risk patients treated with ticagrelor without significant difference in BARC type 3 to 5 bleeding risk (HR, 1.11; 95% CI, 0.75 to 1.65; P=.61). ConclusionThere was still a gap between guideline-indicated therapy and the clinical practice in a sizable subset of patients with acute coronary syndrome who underwent percutaneous coronary intervention. The GRACE risk score could identify patients who would derive benefit from the ticagrelor-based antiplatelet strategy.

Neurosurgical management of proton beam therapy-induced moyamoya syndrome.

Proton beam therapy (PBT) is an increasingly used treatment modality for pediatric patients with brain tumors. Moyamoya syndrome (MMS) is well recognized as a complication of traditional photon radiotherapy, however its association with PBT is less well described. The authors discuss their initial experience with the neurosurgical management of MMS secondary to PBT in a large-volume pediatric neurovascular service. The authors performed a retrospective case review of consecutive children referred for neurosurgical management of MMS after PBT between 2009 and 2022. Patient demographic characteristics, oncological history and treatment, interval between PBT and MMS diagnosis, and MMS management were recorded. Clinical outcome at last review was classified as good if the modified Rankin Scale (mRS) score was ≤ 2 and/or the patient attended mainstream education without additional assistance. Poor outcome was defined as mRS score ≥ 3 and/or the patient received additional educational support. The recorded radiological outcomes included angiographic analysis of stenosis, evidence of brain ischemia/infarction on MRI, and postsurgical angiographic revascularization. Ten patients were identified. Oncological diagnosis included craniopharyngioma (n = 6), optic pathway glioma (1), ependymoma (1), Ewing sarcoma (1), and rhabdosarcoma (1). The median (interquartile range [IQR]) age at PBT was 5.1 (2.7-7.9) years. The median (IQR) age at MMS diagnosis was 7.8 (5.7-9.3) years. The median time between PBT and diagnosis of MMS was 20 (15-41) months. Six patients had poor functional status after initial oncological treatment and prior to diagnosis of MMS. All 10 patients had endocrine dysfunction, 8 had visual impairment, and 4 had behavioral issues prior to MMS diagnosis. Four patients had a perioperative ischemic event: 2 after tumor surgery, 1 after MMS surgical revascularization, and 1 after receiving a general anesthetic for an MRI scan during oncological surveillance. Seven children were treated with surgical revascularization, whereas 3 were managed medically. The incidence of ischemic events per cerebral hemisphere was reduced after surgical revascularization: only 1 patient of 7 had an ischemic event during the follow-up period after surgery. No children moved from good to poor functional status after MMS diagnosis. MMS can occur after PBT. Magnetic resonance angiography sequences should be included in surveillance MRI scans to screen for MMS, and families should be counseled about this complication. Management at a high-volume pediatric neurovascular center, including selective use of revascularization surgery, appears to maintain functional status in these children.

Dengzhan Shengmai capsule versus Aspirin in the treatment of carotid atherosclerotic plaque: A single-centre, non-inferiority, prospective, randomised controlled trial

BackgroundAspirin is an effective antiplatelet agent for the treatment of carotid atherosclerosis. However, the high risk of bleeding events associated with the drug makes it necessary to seek a safer alternative, with similar or more efficacy than aspirin. Dengzhan Shengmai (DZSM) capsules have been widely used to treat carotid atherosclerosis, and if proven to be non-inferior to aspirin, it may be preferable over the latter for carotid atherosclerosis treatment due to its numerous advantages. We conducted a randomised trial to test the non-inferiority of DZSM to aspirin for the treatment of carotid atherosclerotic plaques. MethodsWe performed a single-centre, prospective, open-label, randomised non-inferiority trial. Patients with carotid atherosclerotic plaques were enrolled and randomly assigned (1:1) to receive either DZSM capsules or aspirin. The follow-up period was 12 months. The primary outcome was the mean change in carotid intima-media thickness (IMT). Secondary outcomes included ischaemic events, rate of lumen stenosis, lipid levels, and plaque scores, length, counts, and vulnerability. Adverse events and laboratory test results were recorded as safety outcomes. The non-inferiority of DZSM was demonstrated when the lower limit of the one-sided 97.5% confidence interval (CI) of the difference in IMT between groups was more than -0.06 mm (margin of non-inferiority). This trial has been registered at ClinicalTrials.gov (CHiCTR1900021365). ResultsFrom 1 April 2019 to 30 September 2019, 150 patients were enrolled, and there was no statistical difference in demographics between the groups. Intention-to-treat analysis showed that the decrease in IMT(∆IMT) was 0.216 ± 0.160 and 0.225 ± 0.149 mm in the DZSM and aspirin groups, respectively. The one-sided 97.5% CI for the difference between ∆IMTs was (-0.0593, +∞). The non-inferiority of DZSM was demonstrated (Pnon-inferiority = 0.0234). There was no significant difference in the incidence of ischaemic events between the groups (P = 1.0). The DZSM group had significantly reduced plaque scores (P < 0.0001), length (P < 0.0001), and counts (P < 0.0001), and improved plaque vulnerability (P < 0.0001). The DZSM group also had reduced levels of low-density lipoprotein cholesterol (LDL-C) (P < 0.0001). Finally, the DZSM group had a lower incidence of total adverse events (14.7% vs. 28%, P = 0.046), especially gastrointestinal discomfort (5.3% vs. 16%, P = 0.034). Although there was no significant difference in bleeding events (0 vs. 5.3%, P = 0.120), the DZSM group tended to have a lower incidence. ConclusionThis trial demonstrated that DZSM was not inferior, in efficacy, to aspirin in treating carotid atherosclerotic plaques, and was found to be superior to aspirin in terms of safety. This study provides a new approach for treating carotid plaques, especially in aspirin-intolerant patients.

Impact of &lt;i&gt;CYP2C19&lt;/i&gt; gene polymorphisms on clinical outcomes in patients with myocardial infarction during 12-month follow-up

Highlights. CYP2C19 gene polymorphisms in patients with acute myocardial infarction are common in clinical practice. The article assesses the role of genetic predisposition in the development of ischemic and hemorrhagic events during dual antiplatelet therapy (aspirin and clopidogrel) within the first 12 months after revascularization for acute myocardial infarction.Aim. To evaluate the impact of CYP2C19 gene *1, *2, *3, *17 alleles polymorphism on 12-month clinical outcomes in patients who underwent coronary revascularization due to acute myocardial infarction and took clopidogrel.Methods. 363 patients with acute myocardial infarction undergoing percutaneous coronary intervention were enrolled in the prospectively study in 2010–2012. CYP2C19 gene *1, *2, *3, *17 alleles polymorphism analysis was performed in all study participants. Dual antiplatelet therapy, consisting of aspirin and clopidogrel, was prescribed for 12 months. The follow-up period was 12 months, the incidence of cardiovascular death, non-fatal myocardial infarction, stroke and bleeding was assessed.Results. 12 months after inclusion in the study, the incidence of composite endpoint (defined as cardiovascular death, non-fatal myocardial infarction and stroke) was observed in 18 patients (7% [5%; 11%]; 95% CI) with wild-type CYP2C19 gene and in 12 patients (11% [6%; 18%]; 95% CI) with lost-of-function *2+*3 alleles, with no statistical difference (OR = 1.6 [0.7; 3.6], 95% CI; p = 0.301). Presence of any LOF-alleles did not predict composite endpoint events (OR = 1.56 [0.71; 3.34], 95% CI, p&lt;0.253). Multivariable logistic regression analysis revealed that CYP2C19*2 homozygotes have higher risk of composite endpoint (OR = 6.34, 95% CI [1.57; 22.23], p&lt;0.005) and myocardial infarction (OR = 5.45, 95% CI [1.14; 19.97], p&lt;0.016) compared to *2 heterozygotes and wild-type carriers. 14 patients had major bleedings, required blood transfusion or hospitalization. Patient’s age, increase in creatinine level and gain-of-function (GOF) CYP2C19*17 homozygotic carriage were identified as the predictors of major bleeding during follow-up period.Conclusion. In this study CYP2C19 LOF alleles polymorphism except the CYP2C19*2 homozygotic carriage demonstrated no impact on the incidence of ischemic events during 12-month follow-up in patients with acute MI who underwent successful revascularization. CYP2C19*17 homozygotes demonstrated increased risk of major bleeding only in young individuals with elevated blood creatinine levels.

Effects of Aspirin Therapy on Bypass Efficacy and Survival of Patients Receiving Direct Cerebral Revascularization.

Background: Both patency maintenance and neoangiogenesis contribute to cerebrovascular bypass efficacy. However, the combined impact of the aforementioned two indicators on postoperative revascularization following superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass has been less well elucidated. Meanwhile, there is a paucity of evidence with conflicting results about postoperative aspirin therapy. Objective: The objective of the study was to investigate the correlation between aspirin use and STA-MCA bypass efficacy, including patency, postoperative neoangiogenesis, and follow-up outcomes. Methods: A total of 181 MMD patients (201 procedures) undergoing STA-MCA bypass at our institution (2017–2019) were retrospectively reviewed. The bypass efficacy level and postoperative complications were compared between aspirin and non-aspirin groups. Results: Among 95 PS-matched pairs, the aspirin group presented a significantly more favorable bypass efficacy than the non-aspirin group [odds ratio (OR) 2.23, 95% confidence interval (CI) 1.11–4.61; p = 0.026]. Multivariate logistic regression analysis confirmed the profound impact of aspirin as an independent predictor of bypass efficacy [adjusted OR 2.91, 95% CI 1.34–6.68; p = 0.009]. A remarkable negative correlation was found between bypass efficacy and the rate of ischemic complications (Phi = −0.521). Postoperative aspirin therapy was associated with a non-significant trend toward a lower incidence of ischemic events [OR 0.73, 95% CI 0.23–2.19; p = 0.580]. No significant difference in bleeding rates was observed between aspirin and control groups [OR 1.00, 95% CI 0.12–8.48; p = 1.000]. Conclusion: Among patients undergoing STA-MCA bypass procedures, bypass efficacy is a good predictor of follow-up outcomes. Postoperative aspirin therapy can improve patency, neoangiogenesis, and overall bypass efficacy, thereby protecting against postoperative ischemic complications. Clinical Trial Registration: http://www.chictr.org.cn/, identifier CTR2100046178.

Abstract 164: Impact Of Chronic Kidney Disease On The Risk And Outcomes Of Type-2 Myocardial Infarction In Geriatric Patients With Prior Bypass Grafting

Background: Coronary artery disease associates with increasing age and correlates with CABG being more common in elderly. However, prognostic data of ischemic events post-CABG is limited especially in geriatric patients who are underrepresented in clinical-trials. Furthermore, CKD accelerates coronary atherosclerosis and although treatment practices improved, incidence of ischemic events remain high due to oxygen supple-demand mismatch. Thus, we aim to evaluate impact of CKD on risk of Type-2 Myocardial Infarction (T2MI) in geriatric patients post-bypass grafting. Methods: Data from National Inpatient Sample (2018) was used to identify T2MI-related hospitalizations in geriatric patients with prior history of CABG and CKD. Logistic regression was used to assess the odds of T2MI with CKD. In-hospital outcomes and co-morbidities were compared between CKD &amp; non-CKD cohorts. Results: T2MI-associated hospitalizations among studied population has higher odds when controlled for confounders (OR 1.48, 95%CI: 1.33-1.64, p&lt;0.001). The two cohorts, CKD(n=399485) vs non-CKD(n=676550), had comparable sociodemographics (Table 1b); age at admission (78 vs 77); males (70.6% vs 70%); race- white (77.9% vs 83.5%), black (8.7% vs 5.4%), Hispanic (7.8% vs 6.5%). The odds of adverse cardiac events (cardiac arrest, cardiogenic shock, and dysrhythmia), all-cause mortality, and hospital length-of-stay was higher in CKD cohort with an exception for stroke (Table 1c). Statistical significance was observed (p&lt;0.001) for all co-morbidities (except age) and outcomes. Conclusion: CKD confers an increased risk of T2MI-related hospitalizations and adverse in-hospital outcomes in geriatric patients post-bypass grafting. It finds significance in the need to mitigate risk factors of T2MI and adopt appropriate treatment practices in this population subset.

Impact of Ticagrelor vs. Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention After Risk Stratification With the CHA2DS2-VASc Score.

BackgroundsThe clinical benefit of ticagrelor vs. clopidogrel in unselected patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) remains controversial in the real world. This study was aimed to investigate the impact of ticagrelor vs. clopidogrel in subjects with ACS without atrial fibrillation or flutter (AF) after PCI based on risk stratification using the CHA2DS2-VASc score.MethodsIn 2016–2019, patients who underwent PCI with at least one stent implanted in the General Hospital of Northern Theater Command were classified as low- or high-risk groups according to the CHA2DS2-VASc score. Incidences of 12-month ischemia [cardiac death, myocardial infarction (MI), or stroke], all-cause death, Bleeding Academic Research Consortium (BARC) 2,3,5 bleeding, BARC 3,5 bleeding, and net adverse clinical events (NACEs) (all-cause death, MI, stroke, or BARC 3, 5 bleeding) with aspirin plus different P2Y12 inhibitors (clopidogrel or ticagrelor) were appraised among different risk groups. Propensity score matching (PSM) and Cox multivariate analysis were used to balance the groups.ResultsA total of consecutive 17,037 patients with ACS were enrolled. The optimal cut-off value of the CHA2DS2-VASc score for ischemic events by the Youden test was 3 points. Among patients with high risk (CHA2DS2-VASc ≥ 3, n = 6,151), ticagrelor was associated with slightly lower risks of ischemic events (2.29% vs. 3.54%, P = 0.02) and stroke (0.39% vs. 1.08%, P = 0.01) without excessive risk of BARC 3, 5 bleeding events (2.16% vs. 2.11%, P = 0.92) compared to clopidogrel within 12 months after PCI. For patients with low risk (CHA2DS2-VASc < 3, n = 10,886), a statistically significant difference was seen in the incidence of overall 12-month BARC 2, 3, 5 bleeding events by P2Y12 receptor inhibitor (4.00% vs. 3.26%) with a similar incidence of the ischemic events (1.40% vs. 1.52%). Results in the PSM cohort and the adjustment with Cox multivariate analysis were consistent with the main outcomes.ConclusionHigher CHA2DS2-VASc scores were associated with a higher incidence of 1-year ischemic events for the patients with ACS after PCI. Compared with clopidogrel, ticagrelor was associated with lower ischemic events within 12 months after PCI without excessive risk of bleeding in high-risk patients but shows poor safety with excess bleeding in low-risk patients.

Cisplatin Induced Ischemic Stroke in Germ cell tumour

Germ cell tumors are common among young males with excellent outcomes even in advanced stages. Despite a superb curability rate, treatment-related side effects and complications affect the quality of life. We report a case where Cisplatin-based chemotherapy, the backbone for germ cell tumors treatment, led to ischemic insult. The purpose is to highlight the importance of keeping the incidence of ischemic events following cisplatin-based chemotherapy in differentials for effective management.

The efficacy and safety of ticagrelor versus clopidogrel in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention

Objective: To compare the efficacy and safety of ticagrelor and clopidogrel in elderly Chinese patients with acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI) in the real world. Methods: This study is a post-hoc analysis of a single center, retrospective cohort study. Between March 2016 and March 2018, elderly (age≥65) ACS patients who underwent PCI in the General Hospital of Northern Theater Command were included in the study. The patients were grouped according to P2Y12 receptor inhibitor. The primary endpoints of this study were ischemic events during the 2-year follow-up, which were defined as the composite of cardiac death, myocardial or stroke. The secondary efficiency endpoints included all-cause death and BARC 2, 3, 5 bleeding events. Results: A total of 4 022 elderly (mean age: (71.5±5.3) years) ACS patients were included in this study. Based on the choice of P2Y12 receptor inhibitor, patients were divided into clopidogrel (n=3 201) and ticagrelor (n=821) groups. Incidences of ischemic events (3.2% (26/821) vs. 5.6% (179/3 201), P=0.005) at 2 years were significantly lower in ticagrelor group compared to clopidogrel group. BARC 2, 3, 5 bleeding events (1.7% (14/821) vs. 1.6% (52/3 201), P=0.818) were comparable between the two groups. The incidence of all-cause death (1.5% (12/821) vs. 4.1% (132/3 201), P=0.005) were also lower in the ticagrelor group compared to the clopidogrel group. Clinical outcomes were consistent after adjusting for confounding factors, the incidence of ischemic events (HR= 0.637, 95%CI 0.409-0.991, P=0.046) and all-cause mortality (HR=0.402, 95%CI 0.213-0.758, P=0.005) was significantly lower in the ticagrelor group compared with the clopidogrel group. Risk of BARC 2, 3, 5 bleeding events were similar between the two groups (HR=0.957, 95%CI 0.496-1.848, P=0.897). Conclusion: In real-world clinical practice, for elderly patients with ACS undergoing PCI, ticagrelor use might reduce the incidence of long-term ischemic events and all-cause death without increasing the risk of bleeding.

Effect of prior antiplatelet therapy on large vessel occlusion in patients with non-valvular atrial fibrillation newly initiated on apixaban

IntroductionWe evaluated the effect of prior antiplatelet therapy on large vessel occlusion (LVO) in patients with non-valvular atrial fibrillation (NVAF) newly initiated on apixaban. MethodsPatients with acute LVO with acute stroke due to NVAF or stenosis with NVAF started on apixaban within 14 days of onset were enrolled. We compared incidence of major bleeding, cerebral hemorrhage, ischemic events, cerebral infarction, and all-cause mortality between patients with and without prior antiplatelet therapy for acute LVO. We also compared these events between patients who continued antiplatelet therapy after onset (continued group) and those who discontinued it (discontinued group). Hazard ratios were estimated after adjusting for confounders; interaction was evaluated considering intravenous thrombolysis (IVT) or endovascular treatment (EVT) according to major bleeding. ResultsThe study comprised 686 eligible patients (excluded [n = 194]; enrolled [n = 492]). The antiplatelet group consisted of older patients (mean: 79 vs. 76 years; p = 0.006) and had a higher cumulative incidence of major bleeding (7.3% vs. 2.9%, p = 0.003). The incidence of ischemic events and all-cause mortality was similar between the groups. Among the 109 patients in the antiplatelet group, the cumulative incidence of major bleeding, ischemic events, and all-cause mortality was comparable between continued group (n = 26) and discontinued group (n = 83). There were no significant differences between groups with and without IVT/EVT. However, major bleeding occured more frequently in the antiplatelet group without IVT. ConclusionPrior antiplatelet therapy for LVO in patients with NVAF newly initiated on apixaban was associated with major bleeding, which was more frequent in the antiplatelet group without IVT.