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Bulletin of Experimental Biology and... Jun 2024In in vitro model of short-term therapeutic inhalation of Xe/O mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation...
In in vitro model of short-term therapeutic inhalation of Xe/O mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.01). A slightly weaker but statistically significant reduction in aggregation appeared in response to ristocetin (by ≈12%, p≤0.01) and epinephrine (by ≈9%, p≤0.01). It should be noted that the spontaneous aggregation exceeded the reference values in the control group. Nevertheless, even at minimal absolute values, spontaneous platelet aggregation decreased by 2 times in response to xenon (p≤0.01). The reasons for the decrease of spontaneous and induced aggregation are xenon accumulation in the lipid bilayer of the membrane with subsequent nonspecific (mechanical) disassociation of membrane platelet structures and specific block of its distinct from neuronal NMDA receptor.
PubMed: 38888651
DOI: 10.1007/s10517-024-06101-3 -
EuroIntervention : Journal of EuroPCR... Jun 2024
Topics: Humans; Platelet Aggregation Inhibitors; Clopidogrel; Percutaneous Coronary Intervention; Treatment Outcome
PubMed: 38887879
DOI: 10.4244/EIJ-E-24-00009 -
Digital Health 2024The emergence of cardiovascular risk factors in sub-Saharan Africa suggests an increasing incidence of acute coronary syndromes and STEMI. The aim of the study was to...
INTRODUCTION
The emergence of cardiovascular risk factors in sub-Saharan Africa suggests an increasing incidence of acute coronary syndromes and STEMI. The aim of the study was to define the prevalence of STEMI and to describe the characteristics of patients diagnosed with STEMI within the tele-electrocardiogram (ECG) network in Côte d'Ivoire.
METHOD
A retrospective study was conducted from January 2015 to August 2019. All adult patients managed by one of the six hospitals within the telemedicine network who benefited from a remote interpretation of their ECG by the cardiology department of Bouaké University Hospital were included. The main reason for ECG interpretation, patient and ECG characteristics, diagnosis, response time and treatment were described.
RESULTS
A total of 5649 patients were included. The prevalence of STEMI was 0.7% ( = 44 cases) with a mean age of 58.6 ± 11.8 years and a M/F sex ratio of 1.93. Among STEMI patients, chest pain was the main reason for ECG testing (56.8%). Most ECGs were interpreted within 12 hours (72.8%). The anterior inter-ventricular artery location (59.1%, = 26) was predominant. The Q wave of necrosis was absent in 18% ( = 8) of cases. All patients received double anti-platelet aggregation and 50% ( = 22) additional heparin therapy. No patient underwent primary angioplasty or thrombolysis, 65.9% ( = 29) were referred to the Bouaké Cardiology Department and 34.1% ( = 15) to the Abidjan Heart Institute. Scheduled angioplasty was performed in 20% ( = 3) of patients in Abidjan.
CONCLUSION
Tele-ECG was an effective means of STEMI screening in Côte d'Ivoire. Systematic telethrombolysis of all patients diagnosed could improve their prognosis.
PubMed: 38882247
DOI: 10.1177/20552076241262276 -
The Journal of the Association of... Apr 2024Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug...
Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy Study: A Knowledge, Attitude, and Practice Study among Indian Interventional Cardiologists.
BACKGROUND
Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug management of CAD, including optimizing the duration of antiplatelet treatment regimens in the management of CAD, which is an intricate clinical issue. The available evidence indicates that East Asians have a higher bleeding risk. However, the Indian phenotype differs from that of East Asians, making this data confounding when applied to clinical decision-making among Indian patients. There is a need for a close understanding of Indian interventional cardiologists' perceptions of complex decision-making pertaining to antiplatelet agents among Indian CAD patients in real-world clinical settings.
AIM
This Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy (INDEPTH) study aims to assess the perspective of Indian interventional cardiologists regarding de-escalating from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), approach to decision-making, barriers, and related challenges in CAD management.
METHODS
A cross-sectional knowledge, attitude, and practice (KAP) study survey was carried out among Indian interventional cardiologists practicing across different regions of India. A total of 209 responses were received. Descriptive statistics was used to summarize all the parameters. IBM Statistical Package for the Social Sciences (SPSS) statistics was used for biostatistical analysis.
RESULTS
The study indicated that >90% of CAD patients received DAPT therapy immediately after percutaneous coronary intervention (PCI) (86.1%, < 0.001). About 115 (55%) of the respondents reported using calculator-based scoring for evaluating bleeding risk in patients on DAPT therapy for the management of acute coronary syndrome (ACS) with post-PCI ( = 0.167). Regarding the usual duration of DAPT therapy post-ACS, nearly half of the respondents, 94 (45%), said that 6-12 months is the usual duration for DAPT therapy in post-ACS patients, followed by > 12 months 94 (45%) of the respondents; 17 (8.1%) of the respondents reported it is 3-6 months, and lastly up to 3 months as per four (1.9%) of the respondents ( < 0.001). A total of 128 (61%) of the respondents strongly believe that balancing bleeding with ischemic risk influenced the choice of antiplatelet agent when treating established CAD. As per interventional cardiologists surveyed, the perfect de-escalation time frame for Indian CAD patients with high bleeding risk (HBR) is up to 3 months (35.9%, < 0.001), 6-12 months for medium bleeding risk (48.8%, < 0.001), and >12 months for low bleeding risk (65.6%, < 0.001). Regarding SAPT therapy, almost one-third of the respondents, 65 (31.1%), reported that they prescribed antiplatelet therapy other than aspirin in 20-40% of their SAPT-eligible patients. Furthermore, 69 (33%) of the respondents said that they preferred to prescribe clopidogrel in 50-75% of SAPT-eligible patients. While 64 (30.5%) prescribed in 25-50%, 53 (25.4%) prescribed in <25% and 23 (11%) of the respondents prescribed the drug in >75% of the SAPT-eligible patients. (p < 0.001). "Atorvastatin + clopidogrel" is the most preferred combination of SAPT primarily for the management of CAD among the majority of interventional cardiologists [33%, 95% confidence interval (CI): 1.97-2.24, < 0.001]. The study respondents also indicated a need for Indian-specific guidelines on de-escalating from DAPT to SAPT in CAD management.
CONCLUSION
The INDEPTH study indicated that the majority of CAD patients received DAPT immediately after PCI. The perfect de-escalation time frame for Indian CAD patients with "high-bleeding" risk is up to 3 and 6-12 months for "medium-bleeding" risk and >12 months for "low-bleeding" risk. One-third of respondents used clopidogrel as an antiplatelet agent in 50-75% of SAPT-eligible patients. Atorvastatin + clopidogrel is predominantly the most preferred combination of statin + SAPT for the management of CAD. Although the current international guidelines cover the Indian perspective to some extent, there is a need for Indian-specific guidelines on de-escalating from DAPT to SAPT.
Topics: Humans; India; Platelet Aggregation Inhibitors; Dual Anti-Platelet Therapy; Coronary Artery Disease; Cross-Sectional Studies; Cardiologists; Health Knowledge, Attitudes, Practice; Practice Patterns, Physicians'; Percutaneous Coronary Intervention; Female; Male; Clinical Decision-Making
PubMed: 38881086
DOI: 10.59556/japi.72.0515 -
Molecular and Cellular Biochemistry Jun 2024Acute myocardial infarction is mainly caused by a lack of blood flood in the coronary artery. Angiopoietin-like protein 2 (ANGPTL2) induces platelet activation and...
Acute myocardial infarction is mainly caused by a lack of blood flood in the coronary artery. Angiopoietin-like protein 2 (ANGPTL2) induces platelet activation and thrombus formation in vitro through binding with immunoglobulin-like receptor B, an immunoglobulin superfamily receptor. However, the mechanism by which it regulates platelet function in vivo remains unclear. In this study, we investigated the role of ANGPTL2 during thrombosis in relationship with ST-segment elevation myocardial infarction (STEMI) with spontaneous recanalization (SR). In a cohort of 276 male and female patients, we measured plasma ANGPTL2 protein levels. Using male Angptl2-knockout and wild-type mice, we examined the inhibitory effect of Angptl2 on thrombosis and platelet activation both in vivo and ex vivo. We found that plasma and platelet ANGPTL2 levels were elevated in patients with STEMI with SR compared to those in non-SR (NSR) patients, and was an independent predictor of SR. Angptl2 deficiency accelerated mesenteric artery thrombosis induced by FeCl in Angptl2 compared to WT animals, promoted platelet granule secretion and aggregation induced by thrombin and collogen while purified ANGPTL2 protein supplementation reversed collagen-induced platelet aggregation. Angptl2 deficiency also increased platelet spreading on immobilized fibrinogen and clot contraction. In collagen-stimulated Angptl2 platelets, Src homology region 2 domain-containing phosphatase (Shp)1-Y564 and Shp2-Y580 phosphorylation were attenuated while Src, Syk, and Phospholipase Cγ2 (PLCγ2) phosphorylation increased. Our results demonstrate that ANGPTL2 negatively regulated thrombus formation by activating ITIM which can suppress ITAM signaling pathway. This new knowledge provides a new perspective for designing future antiplatelet aggregation therapies.
PubMed: 38880861
DOI: 10.1007/s11010-024-05034-9 -
Clinical and Translational Science Jun 2024This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral...
This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.
Topics: Humans; Cytochrome P-450 CYP2C19; Atrial Fibrillation; Male; Female; Aged; Coronary Artery Bypass; Middle Aged; Clopidogrel; Postoperative Complications; Genotype; Platelet Aggregation Inhibitors; Platelet Aggregation; Incidence; Aspirin
PubMed: 38877696
DOI: 10.1111/cts.13862 -
Purinergic Signalling Jun 2024P2Y12 receptor (P2Y12R) is an adenosine-activated G protein-coupled receptor (GPCR) that plays a central role in platelet function, hemostasis, and thrombosis. P2Y12R... (Review)
Review
P2Y12 receptor (P2Y12R) is an adenosine-activated G protein-coupled receptor (GPCR) that plays a central role in platelet function, hemostasis, and thrombosis. P2Y12R activation can promote platelet aggregation and adhesion to cancer cells, promote tumor angiogenesis, and affect the tumor immune microenvironment (TIME) and tumor drug resistance, which is conducive to the progression of cancers. Meanwhile, P2Y12R inhibitors can inhibit this effect, suggesting that P2Y12R may be a potential therapeutic target for cancer. P2Y12R is involved in cancer development and metastasis, while P2Y12R inhibitors are effective in inhibiting cancer. However, a new study suggests that long-term use of P2Y12R inhibitors may increase the risk of cancer and the mechanism remains to be explored. In this paper, we reviewed the structural and functional characteristics of P2Y12R and its role in cancer. We explored the role of P2Y12R inhibitors in different tumors and the latest advances by summarizing the basic and clinical studies on the effects of P2Y12R inhibitors on tumors.
PubMed: 38874752
DOI: 10.1007/s11302-024-10027-w -
Journal of the American Heart... Jun 2024Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention...
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
METHODS AND RESULTS
Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS
Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Topics: Aged; Female; Humans; Male; Middle Aged; Acute Coronary Syndrome; Black or African American; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38874073
DOI: 10.1161/JAHA.123.033791 -
Toxicon : Official Journal of the... Jun 2024We investigated the hemotoxic effects of three North American pit vipers in healthy human donor blood. Using experiments focusing on platelet and red blood cell...
We investigated the hemotoxic effects of three North American pit vipers in healthy human donor blood. Using experiments focusing on platelet and red blood cell activity, we found differential effects of these venoms on these cellular components. Platelet aggregation was most induced by C. adamanteus. Platelet activation was highest with C. atrox. Red blood cells had calcium expression and erythrocyte formation most induced by C. adamanteus and A. piscivorus. These results demonstrate the complex interplay of individual cellular effects with clinical presentations seen in envenomings from these species.
PubMed: 38871030
DOI: 10.1016/j.toxicon.2024.107798 -
Clinical and Applied... 2024Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk...
BACKGROUND
Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk of aspirin-induced bleeding and carefully balancing its benefits against potential risks. The objective of this study was to create a practical nomogram for predicting bleeding risk in patients with a history of myocardial infarction treating with aspirin.
METHODS
A total of 2099 myocardial infarction patients with aspirin were enrolled. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation. Boruta analysis was utilized to identify clinically significant features associated with bleeding. Logistic regression model based on independent bleeding risk factors was constructed and presented as a nomogram. Model performance was assessed from three aspects: identification, calibration, and clinical utility.
RESULTS
Boruta analysis identified eight clinical features from 25, and further multivariate logistic regression analysis selected four independent risk factors: hemoglobin, platelet count, previous bleeding, and sex. A visual nomogram was created based on these variables. The model achieved an area under the curve of 0.888 (95% CI: 0.845-0.931) in the training dataset and 0.888 (95% CI: 0.808-0.968) in the test dataset. Calibration curve analysis showed close approximation to the ideal curve. Decision curve analysis demonstrated favorable clinical net benefit for the model.
CONCLUSIONS
Our study focused on creating and validating a model to evaluate bleeding risk in patients with a history of myocardial infarction treated with aspirin, which demonstrated outstanding performance in discrimination, calibration, and net clinical benefit.
Topics: Humans; Nomograms; Myocardial Infarction; Aspirin; Hemorrhage; Female; Male; Middle Aged; Aged; Risk Factors; Platelet Aggregation Inhibitors; Risk Assessment
PubMed: 38870349
DOI: 10.1177/10760296241262789