A 20-year-old man was admitted for a 5-day acute left chest pain. Laboratory test showed an elevated urinary natriuretic peptide of 2527 pg/ml and troponin-T of 5059.0 ng/l. Coronary computed tomography angiography (CCTA) (Fig. 1a and b) on admission demonstrated three giant aneurysms with calcification in the left main (2.8 cm), left anterior descending (2.4 cm), and right (3.3 cm) coronary arteries, the two latter of which and adjacent proximal coronary arteries were occluded by thrombosis, and only faint contrast enhancement in the distal coronary arteries. Cardiovascular MRI (CMR) (Fig. 1c and d) revealed diffuse subendocardial and transmural late gadolinium enhancement (LGE) in both ventricular walls with poor left ventricular wall contraction in segments with LGE (Videos S1 and S2) and left ventricular ejection fraction (LVEF) of 24.5%. Resting myocardial perfusion imaging showed extensive myocardial ischemia in the inferior, high lateral, and septal left ventricular wall (Fig. 1e). Acute myocardial infarction by thrombosis in giant Kawasaki coronary aneurysms was diagnosed. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1.","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_qj0tnb5j"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 2.","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_86d9ctbg"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Fig. 1: Multimodality images of giant Kawasaki coronary artery aneurysms and myocardial infarction in a 20-year-old man. (a) Coronary CT angiography shows giant aneurysms in the left main, left anterior descending, and right coronary arteries, the two latter of which were nearly occluded by thrombosis. (b) Volume-rendered view of whole coronary CT angiography showed occlusion of proximal coronary arteries adjacent to the aneurysms and faint contrast enhancement in the distal coronary arteries. (c and d) Cardiovascular magnetic resonance images show diffuse subendocardial and transmural late gadolinium enhancement in both ventricular walls. (e) Resting myocardial perfusion image shows extensive myocardial ischemia in the inferior, high lateral, and septal LV wall. CT, computed tomography; LV, left ventricular.Both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) were considered technically challenging and high-risk. PCI was limited by the risk of stent malapposition and thrombotic occlusion in lesions with giant aneurysms. Although CABG is the standard of care in complex multivessel aneurysmal disease, which can improve patient outcomes [1], it was not conducted in this patient, considering perioperative heart failure for extensive transmural LGE and severe left ventricular dysfunction, as well as the technical challenge of surgery posed by occlusion of adjacent coronary arteries and poor visualization of distal coronary arteries. After multidisciplinary discussion, and considering the patient’s hemodynamic stability, alternative medical therapy with long-term anticoagulation and antiplatelet agents (clopidogrel bisulfate 75 mg/day and aspirin 100 mg/day, administrated orally) was selected, consistent with current consensus that antithrombotic therapy is central when revascularization cannot be safely performed [1]. Follow-up CCTA 3 months and CMR 1 year after discharge showed essentially unchanged appearance of the aneurysms and distal coronary artery, as well as LGE and poor left ventricular contraction in the myocardium. Previous studies have reported that patients with LVEF less than 30% have significantly reduced long-term survival after CABG, with a 5-year survival rate of approximately 72% [2]. In the present case, despite the markedly reduced LVEF of 24.5%, the patient remained clinically stable during an 8-year follow-up – he experienced no recurrent ischemic events, and the antithrombotic strategy did not undergo adjustments or discontinuations during follow-up. This outcome not only confirmed the efficacy of the applied therapy but also highlighted the potential role of optimized medical therapy in carefully selected cases with left ventricular dysfunction. In addition, further advanced imaging was not performed in this patient because he remained clinically stable without recurrent events. Coronary artery aneurysms in Kawasaki disease are associated with high-risk cardiovascular events; myocardial infarction prevalence increases with aneurysm size [1]. Multimodality imaging plays an essential role in diagnosis, comprehensive evaluation, and surveillance of patient condition. Acknowledgements This work was supported by grants from the 1-3-5 project for disciplines of excellence of West China Hospital, Sichuan University (ZYGD23019) and Sichuan Provincial Science and Technology Plan Project (2024YFFK0259). The materials are available from the corresponding author upon reasonable request. Conflicts of interest There are no conflicts of interest.

Endothelial progenitor cells (EPCs) play a critical role in vascular repair and neovascularization by contributing to endothelial regeneration. While clopidogrel bisulfate is widely used as an antiplatelet agent, its direct cellular effects on EPC biology remain largely unexplored. This study aimed to determine whether clopidogrel bisulfate modulates human EPC proliferation, survival, and intracellular signaling in vitro. Human EPCs were isolated from peripheral blood mononuclear cells and characterized by Dil-ac-LDL uptake and CD34 immunostaining. Cells were treated with clopidogrel bisulfate (0, 5, or 10 µM) for 48h. Proliferation, apoptosis, and cell viability were assessed using microscopy, Annexin V/PI flow cytometry, and CCK-8 assays. Western blotting was used to evaluate apoptosis-related proteins (Bax, Bcl-2) and signaling pathways (p-ERK). Clopidogrel bisulfate-treated EPCs maintained characteristic morphology and exhibited an apparent increase in cell density compared with untreated controls, without significant induction of apoptosis. CCK-8 assay revealed increased absorbance at later reaction time points, indicating enhanced cellular metabolic activity. In addition, under basal conditions, no consistent changes in the Bax/Bcl-2 ratio or ERK phosphorylation were observed. In contrast, under H2O2-induced oxidative stress conditions, clopidogrel bisulfate reduced the Bax/Bcl-2 ratio and increased ERK phosphorylation, suggesting context-dependent modulation of intracellular signaling pathways. These findings suggest that clopidogrel bisulfate influences EPC behavior by modulating metabolic activity and intracellular signaling, particularly under oxidative stress conditions. Beyond its antiplatelet effects, clopidogrel bisulfate may support endothelial repair through EPC-mediated mechanisms as a therapeutic agent in vascular disease.

Structure-corona-function engineering of micelles enables rapid hepatic bioactivation of clopidogrel for emergency antiplatelet therapy.

Simultaneous quantification of acetylsalicylic acid, clopidogrel, ticagrelor and their major metabolites in human plasma by liquid chromatography-tandem mass spectrometry.

Dipyridamole and clopidogrel are two antiplatelet agents that can be prescribed off-label in pediatric practice. As commercially available drugs are unavailable, pediatric formulations must be compounded. Both stability-indicating HPLC dosing assays and microbiological methods were validated and described. Stabilities of dipyridamole and clopidogrel in Syrspend® pH4 were studied. The stability study of clopidogrel involved two complementary HPLC methods (RP-HPLC and chiral HPLC). Oral suspension of 10 mg.mL-1 dipyridamole is stable for 3 months at +2/+8°C before opening, 1.5 month at +2/+8°C after opening, and 15 days at 25°C/60% RH. Oral suspension of 5 mg.mL-1 clopidogrel bisulfate is stable only for 1 month at +2/+8°C before or after opening and for 7 days at 25°C/60% RH.

ABSTRACTDrug–food interactions may compromise therapeutic efficacy, particularly for life‐saving medications such as anticoagulants. Changes in gastric fluid properties, including pH modification and surface film formation, can alter drug dissolution and release. This study evaluated a potential interaction between clopidogrel and spinach and explored the underlying mechanisms. In vitro disintegration and dissolution studies were conducted using HCl and phosphate buffers with and without 5% and 7.5% spinach extract. Drug release was quantified by high‐performance liquid chromatography (HPLC), with six media conditions analyzed in triplicate. Disintegration testing was performed in simulated gastric and intestinal fluids and in the presence of spinach leaves to assess the effect of film formation on tablet wetting and disintegration. In vitro–in vivo extrapolation (IVIVE) was assessed using GastroPlus software. Clopidogrel dissolution decreased with increasing spinach concentration in both media. In HCl buffer, dissolution declined from 99% to 94% and 89%, while in phosphate buffer it decreased from 71% to 66% and 56%. These effects were associated with increased pH (HCl: 1.91, 2.83, 2.98; phosphate: 6.81, 8.83, 6.84), increased solution viscosity, 17.63 to 17.67 and 17.70 in HCl buffer, and from 17.44 to 17.50 and 17.54 in phosphate buffer. Moreover, reduced fluid penetration was due to spinach leaves coverage. IVIVE analysis showed weak correlations (R2 = 0.74 in HCl and 0.69 in phosphate buffer). Spinach reduced clopidogrel dissolution in vitro, with statistically significant effects at 5% spinach in HCl buffer (ANOVA test, p‐value 0.019) and 7.5% in phosphate buffer (ANOVA test, p‐value < 0.001). This interaction appears to be mediated by pH alteration, physical film formation, and potentially metal–drug complexation. Confirmation through in vivo studies is warranted.

Background: Solubility of drugs is an important issue in pharmaceutical industry and the solubility of polymorphs play a critical role in dealing with the solubility issue. This work summerizes the effects of crystal structure on drug’s solubility with special focus on the modeling approaches. Methods: The reported solubility data of polymorphs of drugs (i.e. buspirone HCl, clopidogrel hydrogen sulfate, dabigatran exetilate mesylate, flufenamic acid, glycine, indomethacin, mefenamic acid and sofosbuvir) in mono-/mixed-solvent systems were collected from the literature. The data and modeling results were briefly reviewed and the solubility ratios of the polymorphs were calculated. The applicability of the proposed cosolvency models to simulate the solubility of different polymorphs of a solute in mono- or mixed-solvents at various temperatures were shown employing the collected data. The accuracy of the models was assessed by computing the mean percentage deviations (MPDs) of the simulated and measured solubilities. Results: The overall MPD for correlated solubility data of polymorphs of drugs in mono-solvents at various temperatures using a correlative multi-parameter model was 8.9% and that for mixed-solvents using the Jouyban-Acree model was 6.7%. The results of predictions in mixed-solvents provided acceptable errors (overall MPD of 16.6%) and could be recommended for practical applications in the industry. Conclusion: The provided computational methods provided satisfactory results and could be considered as practical solution in the industrial applications.

Oxidative stress is a critical factor in the progression of cardiovascular diseases, often managed with antiplatelet therapy and natural supplements. This study investigated the effects of Clopidogrel (CLOP), Berberine (BBR), and their combination (CLOP+BBR) on the plasma antioxidant status in male rabbits. Rabbits were divided into four groups: Control, CLOP, BBR, and CLOP+BBR. Following the treatment period, plasma levels of key antioxidant markers, including Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione (GSH), were measured. Additionally, Thiobarbituric Acid-Reactive Substances (TBARS) were quantified as a biomarker for lipid peroxidation. The biochemical analysis revealed that the activity of enzymatic antioxidants (CAT and SOD) and the levels of non-enzymatic GSH remained statistically unchanged (P &gt; 0.05) across all treated groups compared to the control. In contrast, a significant reduction (P &lt; 0.05) in plasma TBARS levels was observed in the BBR-treated group (3.272 0.036) and the combination group (3.820 0.038) relative to the control (4.578 0.024) and CLOP (4.641 0.087) groups. Clopidogrel alone did not exhibit a significant impact on lipid peroxidation or antioxidant enzyme profiles. The findings suggest that while Berberine and its combination with Clopidogrel do not significantly modulate the primary antioxidant enzyme system, they exert a significant reduction in lipid peroxidation. This highlights the potential of Berberine as a protective agent against oxidative membrane damage without interfering with the baseline antioxidant defenses.

BackgroundLactobacillus paracasei (LP) may affect the efficacy of clopidogrel (CLP).Methods Forty Sprague-Dawley (SD) rats were randomly divided into control group, LP group, CLP group, LP (pretreatment) + CLP group, and CLP + LP(posttreatment) group (n=6-8). The administration doses of CLP and LP in rats were 6.75 mg/kg/d and 109 CFU/d, respectively, for 14 consecutive days. Tail vein blood was collected to detect blood drug concentration, platelet function. Then, a thrombosis model was constructed using 20% FeCl₃, the complete vascular occlusion time, thrombus weight, and thrombus inhibition rate, inflammatory factors, gut microbiota, short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO) and mucosal barrier were evaluated.Results Compared with the CLP group, the blood concentrations of AM and CA in the combined group were significantly decreased, while platelet aggregation (MPA) and platelet reaction index (PRI) were significantly increased. After model construction, the thrombosis formation time was significantly prolonged, the thrombus weight was significantly reduced, and the thrombus inhibition rate was significantly; the secretions of TNF-α, IL-1β, P-selectin, GPIIb/IIIa, and D-dimer were significantly decreased in the combined group. The structure of gut microbiota also changed significantly after CLP treatment, and LP combined with CLP could improve the dysbiosis caused by CLP through increasing SCFAs and decreasing TMAO. In addition, the expressions of ZO-1, Occludin, and P-gp were increased in the combined groups. It should be noted that there is a directional discrepancy between the changes in platelet function indices (MPA and PRI) and in vivo thrombosis outcomes, which may be related to the multi-factorial regulation of in vivo thrombosis.ConclusionLP may regulate the structure of gut microbiota (increasing SCFA-producing bacteria and inhibiting TMAO-producing bacteria), thereby protecting the intestinal mucosal barrier, inhibiting inflammatory responses, and cooperatively acting with CLP to inhibit platelet activation and improve coagulation function, although the specific mechanism needs further verification.

In recent years, model-informed strategies such as the model integrated bioequivalence (MIBE) approach have gained significance due to their ability to enable decision making, streamline drug product development, and to waive bioequivalence studies, as applicable. In this work, we demonstrate the successful application of the MIBE approach that led to the waiver of a repeat fasting and fed bioequivalence studies for clopidogrel bisulfate 300 mg tablets. In the pivotal bioequivalence study, pharmacokinetic sampling in fasting and fed conditions was performed until 12 h, shorter than the recommended sampling up to at least three half-lives of the drug. The mean half-life of reference listed drug clopidogrel was 6 h. During dossier review, a query was received from the regulatory agency to assess the impact of early termination of the study on AUC0-inf and bioequivalence assessment, although the pivotal study demonstrated average bioequivalence. To address this, a population pharmacokinetic model was developed under fasting and fed conditions based on the pilot study data that included data until 24 h. Further, the pivotal study pharmacokinetic parameters were predicted based on a model developed with pilot data and complete profiles until 10 half-lives were simulated. The model-derived parameters were utilized to assess preserving Type-1 error rate at 5% and bioequivalence was simulated. The simulations demonstrated average bioequivalence under fasting and fed conditions, and the 90% confidence intervals within 80%-125%. Overall, the MIBE approach demonstrated that truncated sampling till 12 h did not compromise the interpretability of pivotal study, thereby alleviating the need for a repeat bioequivalence study.

BackgroundAnimal models are essential for evaluating endovascular device safety and efficacy. Rats offer advantages, such as genetic manipulability, lower cost, and shorter healing and breeding cycles, compared to large animals. These features support studying aneurysm healing mechanisms and enable high-throughput testing. We developed an optimal rat aneurysm model for device evaluation.MethodsSaccular aneurysms were created at the origins of the left renal artery (LRA) with acetylsalicylic acid (ASA) (LRA/ASA group, n = 7); the right common iliac artery (RCIA) with ASA alone (RCIA/ASA group, n = 6) or ASA plus clopidogrel (CLP) (RCIA/ASA + CLP group, n = 7); and the left common iliac artery (LCIA) with ASA + CLP (LCIA/ASA + CLP group, n = 7). The origins of these arteries were surgically exposed. During temporary ligation of the vessel origin, the vessel was bisected and endoluminal elastase was incubated in the proximal stump for 10 min, followed by release of the proximal ligation and permanent ligation of the stump. Angiographical and histological analysis were performed 4 weeks post-procedure.ResultsFollow-up digital subtraction angiography revealed mean ± standard deviation aneurysm height/neck dimensions of 1.2 ± 0.4/1.2 ± 0.1, 2.9/3.1, 2.3 ± 0.6/1.9 ± 0.3, and 2.1 ± 0.6/2.0 ± 0.4 mm for the LRA/ASA, RCIA/ASA, RCIA/ASA + CLP, and LCIA/ASA + CLP groups, respectively. The survival rate was 29%, 17%, 71%, and 86% in the LRA/ASA, RCIA/ASA, RCIA/ASA + CLP, and LCIA/ASA + CLP groups, respectively. Histopathological analysis of these aneurysms confirmed the absence of the internal elastic lamina and revealed aneurysmal changes in the arterial wall, resembling the pathological findings observed in human aneurysm specimens.ConclusionsCommon iliac aneurysm models with ASA + CLP can be used to evaluate the safety and efficacy of endovascular devices.

The goal of the current work was to create and validate a quick, sensitive, and environmentally friendly reverse-phase “high-performance thin-layer chromatography (HPTLC)” approach for the simultaneous measurement of rosuvastatin (ROS) and clopidogrel (CLOP) in their fixed-dose combination (FDC) capsules. Eight different greenness and whiteness tools, such as the analytical eco-scale (AES), chloroform toxicity (ChlorTox), the analytical GREEnness (AGREE), the modified green analytical procedure index (MoGAPI), the complex MoGAPI, the blue applicability grade index (BAGI), the carbon footprint reduction index (CaFRI), and the click analytical chemistry index (CACI) were utilized to evaluate the method's greenness and whiteness profiles. The suggested strategy was linear for both medications in the 25–1000 ng/band level. The method was proven to be reliable, sensitive, accurate, precise, and eco-friendly. The results of greenness and whiteness tools, such as AES (87), ChlorTox (0.86 g), AGREE (0.72), MoGAPI (85), complex MoGAPI (90), BAGI (77.5), CaFRI (89), and CACI (91) demonstrated that the current method had the unparalleled greenness and whiteness profiles. Using the proposed methodology, it was found that the assay of CLOP and ROS in FDC products A and B was ranged from 98.41 to 101.02%. These results confirm that the suggested approach is appropriate for concurrently analyzing ROS and CLOP. The work's findings showed that the suggested approach might be used to consistently analyze CLOP and ROS in commercial dosage forms.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13065-025-01700-1.

Understanding the Role of Disintegrant in Resolving the Sticking of Clopidogrel Bisulfate Tablet

BackgroundThis study investigates the effects of Ginkgo Diterpene Lactone Meglumine (GM) combined with Clopidogrel (CLO) on hemodynamics, neurocytokines, and inflammatory responses in patients with cerebral infarction (CI) complicated by coronary heart disease (CHD).MethodsA total of 152 patients diagnosed with CI complicated by CHD, admitted to our hospital between January 2024 and October 2024, were enrolled in the study. Among them, 81 patients received CLO monotherapy (control group), while the remaining 71 patients were treated with a combination of CLO and GM (observation group). Hemodynamic parameters, including plasma viscosity (PV), whole blood high (WBHSV) and low shear viscosity (WBLSV), as well as reduced viscosity (RV), were measured before and after treatment. Platelet adhesion test (PAdT) and platelet aggregation test (PAgT) were also performed. Inflammatory markers and neurocytokines were assessed using enzyme-linked immunosorbent assays, and adverse reactions during treatment were documented.ResultsAfter treatment, both groups exhibited significant reductions in PAdT, PAgT, PV, WBHSV, WBLSV, and RV compared to baseline (P<0.05). However, PAdT, PAgT, WBHSV, WBLSV and RV were lower in the observation group compared to the control group (P<0.05). Additionally, the observation group showed lower levels of neuron-specific enolase, glial fibrillary acidic protein, tumor necrosis factor-a, and hypersensitive C-reactive protein, along with higher levels of brain-derived neurotrophic factor, compared to the control group (P<0.05). No significant difference was observed in the incidence of adverse reactions between the two groups (P>0.05).ConclusionsThe combination of GM and CLO is more effective than CLO monotherapy in improving hemodynamics, enhancing neurological function, and mitigating inflammatory responses in patients with CI complicated by CHD.

Clopidogrel, an antiplatelet agent widely prescribed for thromboembolic disorders, holds a substantial market presence in Indonesia, with a valuation of IDR 4.52 trillion. While plavix (branded form) remains as one of the leading treatments for such conditions, its high cost makes it unaffordable for a significant portion of Indonesia’s population. This underscores the necessity for generic alternatives that mimic the properties of the branded product to ensure broader accessibility and affordability for patients. To achieve this, generic clopidogrel bisulfate tablets must undergo the same crucial biopharmaceutical stages such as disintegration, drug release, aqueous dissolution, and systemic absorption to achieve therapeutic efficacy similar to the branded version. Despite being the most expensive tablet, the branded form serves as a standard reference to evaluate the dissolution profile, quality, and efficacy of locally manufactured generic formulations. This study investigates the dissolution profile and physical properties of generic clopidogrel bisulfate tablets produced by PT Phapros TBK, compared to a branded clopidogrel bisulfate product licensed by Sanofi in France. Quality attributes including weight and size uniformity, hardness, and disintegration time were assessed as per the Indonesian Pharmacopoeia (5th edition) standards. Dissolution tests were conducted at pH levels of 1.2, 4.5, and 6.8, with 12 sample replications at each interval, to determine bioequivalence between the two formulations. Through this research, the aim is to illuminate the bioequivalence of generic and branded clopidogrel products in Indonesia, offering insights into their interchangeability and potential clinical impact in a high-demand market.

BackgroundThe patient-associated prevalence of Clopidogrel (CPG)—and Aspirin (ASS)—nonresponse is not well understood and varies depending on the patient population. The influence of responder status for platelet inhibition in patients eligible for carotid artery stenting (CAS) on post-interventional cerebral ischemia is unknown.MethodsWe conducted a retrospective, mono-center analysis of all patients with response-test undergoing elective CAS between 2010 and 2024 and available MRI before and after CAS. Study groups were formed according to ASS- and CPG-response. Cerebral ischemia patterns were compared between study groups in univariate analysis and patient-associated co-morbidities were tested for association with drug resistance or infarction frequency.ResultsIn total, 50/68 (73.5%) of patients showed adequate response to ASS and CPG. Non-response to CPG was higher than to ASS (clopidogrel resistance rate: 14.8%, aspirin resistance rate: 9.2%). All patients with non-response were bridged with GP IIb/IIIa antagonist tirofiban during CAS. Under these conditions, the responder status did not influence post-interventional cerebral infarction patterns.ConclusionAntiplatelet non-response, especially for CPG, is very frequent in patients undergoing CAS. When bridging patients with tirofiban during intervention, responder status had no influence on post-interventional cerebral infarction patterns.

Antiplatelet therapy plays an important role in preventing the progression of ischemic stroke. However, the effectiveness of different types of antiplatelet agents in improving clinical outcomes still requires further investigation. This study aimed to analyze the relationship between the type of antiplatelet used and the clinical outcomes of hospitalized ischemic stroke patients, based on changes in the National Institutes of Health Stroke Scale (NIHSS) score and length of stay (LoS). This research was a retrospective cross-sectional observational study involving 92 hospitalized patients with ischemic stroke. Patients were grouped based on the antiplatelet therapy received: Clopidogrel (CPG) (n=58), Aspirin (n=17), and dual antiplatelet therapy (DAPT) with Clopidogrel + Aspirin (n=17). Of the total patients, 43 (46.7%) showed improvement in NIHSS score, while 49 (53.2%) did not. The mean LoS was 7.033 days. The proportion of patients with NIHSS improvement by treatment group showed that the CPG group had the highest percentage of improvement, with 30 out of 58 patients (51.72%), compared to Aspirin 7/17 (41.2%) and DAPT 6/17 (35.3%). However, statistical analysis revealed no significant association between the type of antiplatelet and NIHSS improvement (p = 0.431). In addition, Kruskal-Wallis analysis revealed no significant association between LoS and antiplatelet type (p = 0.429). These findings suggest that other factors may play a more substantial role in determining the clinical outcomes of ischemic stroke patients.

The present analysis of the ARCANGELO study aims to investigate the effect of switching to different oral P2Y12 inhibitors when using cangrelor during PCIs in patients with ACS. Out of the 995 patients meeting the criteria for this investigation, 138 transitioned to Clopidogrel (CLO), 127 to rasugrel (PRA), and 730 to Ticagrelor (TICA). Compared to the patients on PRA or TICA, users of CLO were older (median (Q1-Q3) 74(64-81) years CLO, 59(54-65) years PRA, 65(56-73) TICA; p<0.0001), had more comorbidities (37.0% CLO, 17.3% PRA, 18.9% TICA, p<0.0001), and had more frequently an NSTEMI diagnosis (68.1% CLO vs 33.1% PRA vs 35.9% TICA, p<0.0001). Five moderate bleeds were recorded without any severe episodes. There were no significant differences in the bleeding rate when switching to the different oral P2Y12 inhibitors (2.2% CLO, 5.3% TICA, 7.9% PRA, p = 0.0705) while different incidences of MACEs (4.3% CLO, 1.1% TICA, 0% PRA, p = 0.0113) and NACEs (4.3% CLO, 1.8% TICA, 0% PRA, p=0.0321) were observed during the 30 days of the study. The use of cangrelor and the switch to any oral P2Y12 inhibitor in compliance with the EU SmPC is safe, with a low risk of ischemic events in routine clinical practice.

Patients with symptomatic vertebrobasilar artery stenosis not only experience a first stroke event, but also have a high risk of recurrent stroke. Even though interventional techniques have been widely used in the treatment of cerebral infarction, the therapeutic efficacy for symptomatic vertebrobasilar artery stenosis patients are not superior to that achieved with simple drug therapy. However, the optimal choice of drugs and the duration of their use in a pure drug regimen remain unclear. This retrospective study analyzed data from Heyuan People's Hospital (2021-2023) on patients with vertebrobasilar artery stenosis. Patients were grouped by treatment duration (30/90 days ticagrelor vs. 90 days clopidogrel), all receiving aspirin. Outcomes included ischemic events, bleeding, and complications. SPSS version 22.0 was employed for statistical analysis. This study included 217 patients with symptomatic vertebrobasilar artery stenosis. Clinical features and outcomes of efficacy and safety analyses were conducted. No significant differences in baseline data or safety outcomes were found. However, a significant difference in endpoint events was observed within 90 days for specific subgroups of symptomatic intracranial vertebrobasilar artery stenosis and CYP2C19 gene deletion. For patients with symptomatic vertebrobasilar artery stenosis, the ticagrelor plus aspirin regimen may provide an alternative therapeutic option to the aspirin plus clopidogrel bisulfate regimen. Furthermore, this regimen may represent a favored treatment choice for specific patient subpopulations.

Implementation of breastfeeding recommendations is hampered by-among others-lacking information regarding medicine safety during breastfeeding. This article describes the clinical and pharmacokinetic data of breastfeeding mothers using clopidogrel (CLP) as secondary prevention following (suspicion of) a cerebrovascular accident. A 29-year-old and 42-year-old woman were chronically treated with 75mg CLP once daily. Human milk samples were collected at 7 and 9months (patient 1), and at 14 months postpartum (patient 2). Each sampling period, two maternal blood samples as well as one infant blood sample were collected. Concentrations of CLP, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM) derivatized were analyzed using liquid chromatography with tandem mass spectrometry. The average steady-state concentration in human milk was 0.96 and 7.40ng/mL for CLP and CCA, respectively. CAM concentrations in all but two milk samples were below the limit of detection (LOD; 0.004ng/mL). In the infant plasma sample, CCA level was 0.05ng/mL but CLP and CAM were undetectable (CLP LOD: 0.003ng/mL). The mean daily infant dosage (DID) was 82.3, 585.6 and 1.5ng/kg/day for CLP, CCA and CAM, respectively, and the relative infant dose (RID) for CLP-related exposure remained well below 1%. The estimated infant exposure to CLP and its metabolites via human milk was low in both cases. Although this low exposure was supported by the observed infant plasma concentration, additional studies should confirm CLP safety via human milk, especially considering known variable pharmacokinetics and ontogeny of metabolizing enzymes in infants.