Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.

BACKGROUND AND PURPOSE: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions. METHODS: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes. RESULTS: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54). CONCLUSIONS: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Traditional and Non-Traditional Lipid Parameters in Relation to Parenchymal Hemorrhage Following Endovascular Treatment for Acute Ischemic Stroke in Anterior Circulation.

Purpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT. Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve. Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk. Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.

Impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease patients complicated with end-stage renal disease.

It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.

Effect of statins combined with PCSK9 inhibitors on the prognosis of patients with acute coronary syndromes after interventional therapy.

Acute coronary syndromes (ACS) are a leading cause of morbidity and mortality worldwide. It has been clinically confirmed percutaneous coronary intervention (PCI) can alleviate the symptoms of ACS, but there are still some patients with slow blood flow or no-reflow after surgery, which has adverse effects on the prognosis of patients. This study aimed to investigate the effect of statins combined with PCSK9 inhibitors on the prognosis of patients with ACS after interventional therapy. A total of 208 ACS patients treated in our hospital from January 2021 to December 2022 were separated into observation and control groups. Patients in the control group received oral rosuvastatin 20 mg/ day. Patients in the observation group received PCSK9 inhibitor elozumab (Repatha) 140 mg, subcutaneously injected twice a week. The levels of inflammatory factors, cardiac function indexes, clinical effectiveness rate, adverse events, and complications were compared before and after treatment. After 1 week of treatment and 4 weeks of follow-up, the levels of inflammatory indicators in the observation group declined relative to the control group (P < 0.05 and P < 0.01). After 4 weeks, LVEF in the observation group was elevated in comparison to the control group, while LVEDD in the observation group declined compared to the control group (P < 0.05). The incidence of adverse events after treatment in the observation group declined relative to the control group (P < 0.05). The incidence of complications in the observation group declined in contrast to the control group (P < 0.05). Statins combined with PCSK9 inhibitors significantly reduce LDL-C levels in ACS patients undergoing PCI without increasing cardiovascular events or major adverse clinical effects.

Effects of ilaprazole on the steady-state pharmacodynamics of clopidogrel in healthy volunteers: An open-label randomized crossover study.

Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel. Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 µmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing. Results: IPA was comparable between the two regimens at 0, 10 and 24 h (p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens. Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000031482].

Simultaneous determination of clopidogrel, 2-oxo-clopidogrel, and the thiol metabolite of clopidogrel in human plasma by LC-MS/MS.

Clopidogrel is a pro-drug which needs two-step metabolism to produce the active thiol metabolite. This study aimed to explore an efficient method to simultaneously determine the plasma clopidogrel, 2-oxo-clopidogrel (2-Oxo-CLP), and the clopidogrel active metabolite (CAM). A high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS) was therefore developed. The analytes were extracted from plasma by using methyl tert-butyl ether (MTBE). Chromatographic separation was performed on a C18 column under an isocratic elution, accompanied with acetonitrile and deionized water containing 0.1% formic acid. After optimizing the condition of LC-MS/MS, a stable linearity was observed in the standard curves over the concentration ranges of 0.05 to 50.0 ng/mL for clopidogrel, 0.5 to 50.0 ng/mL for 2-Oxo-CLP, and 0.5 to 100 ng/mL for clopidogrel active metabolite derivative (CAMD). The retention time was 4.78 minutes, 3.79 minutes, 3.59 minutes, and 4.82 minutes for clopidogrel, 2-Oxo-CLP, CAMD, and internal standard, respectively. Both the relative standard deviation and the relative error were within the requirement of operating criteria. No significant degradation of clopidogrel, 2-Oxo-CLP, and CAMD occurred under different storage conditions. This method was successfully validated in 3 patients with coronary artery disease. The results showed that the current LC-MS/MS method was efficient for simultaneously detecting clopidogrel, 2-Oxo-CLP, and CAM with fine linearity, accuracy, precision, and stability.

Three-dimensional Fusion of Myocardial Perfusion SPECT and Invasive Coronary Angiography Guides Coronary Revascularization.

BACKGROUND: SPECT myocardial perfusion imaging (SPECT MPI) and invasive coronary angiography (ICA) provide complementary clinical information in the diagnosis of coronary artery disease (CAD). We have developed an approach for 3D fusion of perfusion data from SPECT MPI and coronary anatomy from ICA. In this study, we aimed to evaluate its clinical value when compared to the traditional side-by-side readings. METHODS: Thirty-six CAD patients who had at least one stenosis ≥ 50% were retrospectively enrolled. Based on the presence of a perfusion defect in a territory subtended by a coronary vessel, all vessels were classified as matched, unmatched, or normal groups via both the fusion and side-by-side analysis. The treatments recommended by the fusion and side-by-side analysis were compared with those that the patients received. Major adverse cardiac events (MACE), defined as all-cause death, myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization, were assessed. RESULTS: The overall vessel-based concordance was 78.7% between the fusion and side-by-side analysis. Compared with the side-by-side analysis, 23 coronary arteries (29 equivocal segments) of 19 patients were reclassified via fusion of data. In the matched, unmatched, and normal groups, the numbers of vessels with hemodynamically significant stenosis which caused reversible defect were 37 vs 53, 28 vs 14, and 43 vs 41 (P < .01) when comparing the side-by-side analysis with the fusion, and the revascularization ratios per vessel were 69% vs 88%, 29% vs 10%, and 2% vs 2% between them. During the five-year follow-up, 8 patients (22.2%) experienced MACE. Patients who received the same treatment as the guidance of 3D fusion results (n = 22) had superior outcomes when compared with those who did not (n = 14) (P < .01). CONCLUSIONS: Compared with the side-by-side analysis, the 3D fusion of SPECT MPI and ICA provided incremental diagnostic and prognostic value.

An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention.

OBJECTIVE: This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI). DESIGN: A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding. RESULT: 1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PLADP) 25.5-37.4%)] and outside the window group (OW) (PLADP < 25.5% or ≥ 37.5%). The incidence of NACE was 16.8 and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW group was significantly lower [0.69 (95% CI, 0.54-0.89, P = 0.004)] than that in the OW group during 12-month follow-up. CONCLUSION: An optimal therapeutic window of 25.5-37.4% for PLADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov NCT01968499 . Registered 18 October 2013 - Retrospectively registered.

Pharmacodynamic effects of indobufen compared with aspirin in patients with coronary atherosclerosis.

PURPOSE: This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis. METHODS: In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PLAA), and the secondary outcomes included plasma thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 (11-dh-TXB2) levels at the end of each treatment.  RESULTS: In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PLAA whereas indobufen group had significantly less suppressed PLAA. Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB2. All treatment regimens produced similar inhibition of 11-dh-TXB2. In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB2 at 8 h and 12 h after the last dose. CONCLUSIONS: Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily.

MicroRNA­133b alleviates doxorubicin­induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2.

Doxorubicin is one of the most important chemotherapeutic drugs for the treatment of malignant tumors, but the cardiotoxicity of doxorubicin severely limits its clinical application. Increasing numbers of microRNAs (miRNAs/miRs) have been found to be dysregulated in doxorubicin­treated cardiomyocytes or animal hearts. The current study aimed to investigate the role of miR­133b in doxorubicin­induced cardiomyocyte injury. Doxorubicin was used to treat HL­1 cardiomyocytes to mimic cardiomyocyte injury in vitro. A mouse model of cardiac injury was generated by chronic intraperitoneal injections of doxorubicin. Masson's trichrome staining was performed on cardiac tissues to reveal cardiac fibrosis. Bioinformatics analysis and luciferase reporter assays were applied to explore the downstream targets of miR­133b. Flow cytometry and western blotting were conducted to detect cardiomyocyte apoptosis. Protein expression levels of collagen I, III and IV, and fibronectin were detected to reveal extracellular matrix deposition. The results revealed that doxorubicin decreased miR­133b expression in the treated HL­1 cardiomyocytes and mouse hearts. Overexpression of miR­133b restrained cardiomyocyte apoptosis, inhibited collagen accumulation and alleviated cardiac fibrosis in vivo. Mechanistically, polypyrimidine tract binding protein 1 (PTBP1) and transgelin 2 (TAGLN2) were confirmed to bind to miR­133b after prediction and screening. Moreover, miR­133b negatively regulated the protein expression levels of PTBP1 and TAGLN2. Finally, overexpression of PTBP1 or TAGLN2 reversed the effects of miR­133b on apoptosis and collagen accumulation. Thus, the current results indicated that miR­133b alleviated doxorubicin­induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2, implying that miR­133b may be a potential biomarker for doxorubicin­induced cardiac injury.