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BACKGROUND: This systematic review and meta-analysis aimed to compare the efficacy and safety of cangrelor as compared to ticagrelor in patients with ST-elevated myocardial infarction (STEMI) who underwent percutaneous intervention. METHODS: PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant head-on-comparison or swapping studies. The primary outcome was the rate of high platelet reactivity (HPR) at specific time intervals after stopping cangrelor infusion during the first 24 h. Secondary outcomes were the risks of thrombosis, all-cause mortality and bleeding. Pooled odds ratios (ORs) were calculated using random-effects models. RESULTS: A total of 1018 studies were screened and eight were included in the analysis. There were four head-on-comparison studies and four swapping studies. There was no significant difference in the proportion of patients achieving a high platelet reactivity in swapping studies [OR, 0.71 (95% CI 0.04, 13.87), p = 0.82, i2 = 88%]. In head-on-comparison studies, PRU from Fig. 2B shows there was no significant reduction in high platelet reactivity [mean difference - 77.83 (95% CI - 238.84, 83.18), p < 0.001, i2 = 100%]. PRU results from (Fig. 2C) show a mean difference of 7.38 (95% CI - 29.74, 44.51), p < 0.001, i2 = 97%. There was no significant difference in the risks of thrombosis [OR, 0.91 (95% CI 0.20, 4.13), p = 0.81, i2 = 0%], all-cause mortality [OR, 3.52 (95% CI 0.44, 27.91), p = 0.24, i2 = 26%] and bleeding [OR, 0.89 (95% CI 0.37, 2.17), p = 0.93, i2 = 0%] between the two groups as revealed in the head-on-comparison studies. CONCLUSION: The efficacy and safety profiles of cangrelor and ticagrelor were similar in patients with STEMI.
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Antiplatelet therapy is the foundational treatment for the prevention and treatment of coronary and cerebrovascular ischemic events in patients with coronary heart disease, ischemic stroke, and transient ischemic attack (TIA). However, with more and more studies reporting an increased risk of thrombosis in some patients due to poor response to therapeutic agents, the selection of appropriate P2Y12 inhibitors has become a major challenge that needs to be addressed urgently. Currently, commonly used oral P2Y12 inhibitors include clopidogrel, ticagrelor, and prasugrel. Assessing patients' risk factors before the development of treatment regimens by effectively predicting the risk of high platelet reactivity with specific P2Y12 inhibitors in advance to avert the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) is the key point to the problem. Up to now, methods available for predicting platelet reactivity include genetic testing, platelet function testing, and risk scores. This review provides a summarization of the existent available identification methods and analyzes the advantages and drawbacks of different methods in specific clinical settings, intending to guide the rational clinical application of P2Y12 receptor inhibitors.
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Síndrome Coronario Agudo , Fibrilación Atrial , Intervención Coronaria Percutánea , Humanos , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/uso terapéutico , Quimioterapia Combinada , Resultado del Tratamiento , Síndrome Coronario Agudo/tratamiento farmacológicoRESUMEN
AIMS: Several scoring systems, including the ABCD-GENE and HHD-GENE scores incorporating clinical and genetic factors, have been developed to identify patients likely to have high platelet reactivity on P2Y12 inhibitors, leading to increased risks of ischemic events. However, genetic testing is not widely available in daily practice. We aimed to evaluate the differential impact of clinical factors in the scores on ischemic outcomes in patients treated with clopidogrel and prasugrel. METHODS: This bi-center registry included 789 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention and treated with either clopidogrel or prasugrel at discharge. The relations of the number of clinical factors included in the ABCD-GENE (age ≥ 75 years, body mass index ï¼30 kg/m2, chronic kidney disease, and diabetes) and HHD-GENE (hypertension, hemodialysis, and diabetes) scores to the primary endpoint of major cardiovascular events after discharge, a composite of death, recurrent MI, and ischemic stroke, were evaluated. RESULTS: The number of clinical factors in the ABCD-GENE score was not predictive of ischemic outcomes after discharge in patients treated with clopidogrel and/or prasugrel, while the increase in the number of clinical factors of the HHD-GENE score was associated with an increased risk of the primary endpoint in a stepwise manner in patients on a P2Y12 inhibitor. CONCLUSIONS: Clinical factors listed in the HHD-GENE score may help stratify ischemic risks in patients with acute MI treated with clopidogrel and prasugrel, whereas risk stratification without genetic testing in patients treated with clopidogrel may be challenging.
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Síndrome Coronario Agudo , Diabetes Mellitus , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Anciano , Clopidogrel/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Resultado del Tratamiento , Infarto del Miocardio/tratamiento farmacológico , Isquemia/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of this study was to assess the association between high on-aspirin treatment platelet reactivity (HAPR) and the subsequent risk of restenosis after percutaneous coronary intervention (PCI) with predominantly drug-eluting stents. BACKGROUND: The association between HAPR and subsequent risk of restenosis after PCI is unclear. METHODS: This study included 4839 patients undergoing PCI (02/2007-12/2011) in the setting of the Intracoronary Stenting and Antithrombotic Regimen-ASpirin and Platelet Inhibition (ISAR-ASPI) registry. Platelet function was assessed with impedance aggregometry using the multi-plate analyzer immediately before PCI and after intravenous administration of aspirin (500 mg). The primary outcome was clinical restenosis, defined as target lesion revascularization at 1 year. Secondary outcomes included binary angiographic restenosis and late lumen loss at 6- to 8-month angiography. RESULTS: The upper quintile cut-off of platelet reactivity measurements (191 AU × min) was used to categorize patients into a group with HAPR (platelet reactivity > 191 AU × min; n = 952) and a group without HAPR (platelet reactivity ≤ 191 AU × min; n = 3887). The primary outcome occurred in 94 patients in the HAPR group and 405 patients without HAPR (cumulative incidence, 9.9% and 10.4%; HR = 0.96, 95% CI 0.77-1.19; P = 0.70). Follow-up angiography was performed in 73.2% of patients. There was no difference in binary restenosis (15.2% vs. 14.9%; P = 0.79) or late lumen loss (0.32 ± 0.57 vs. 0.32 ± 0.59 mm; P = 0.93) between patients with HAPR versus those without HAPR. CONCLUSIONS: This study did not find an association between HAPR, measured at the time of PCI, and clinical restenosis at 1 year after PCI.
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Reestenosis Coronaria , Intervención Coronaria Percutánea , Humanos , Aspirina , Inhibidores de Agregación Plaquetaria/uso terapéutico , Fibrinolíticos/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Sistema de Registros , Reestenosis Coronaria/diagnóstico , Reestenosis Coronaria/etiología , Reestenosis Coronaria/prevención & control , Resultado del Tratamiento , Angiografía CoronariaRESUMEN
Introduction: Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS. Materials and methods: In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y12. Results: The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 µM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed. Conclusion: In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02457130].
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OBJECTIVE: Apolipoprotein E (APOE) loci, including rs429358 (Æ4) and rs7412 (Æ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. METHODS: A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. RESULTS: After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Æ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048-0.715, P = 0.014; HR = 0.435, CI: 0.234-0.812, P = 0.009, respectively) than Æ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Æ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Æ4 noncarriers. CONCLUSIONS: Our results demonstrated that APOE*Æ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Æ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.
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Apolipoproteína E2 , Aspirina , Enfermedades Cardiovasculares , Apolipoproteína E2/genética , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Factores de RiesgoRESUMEN
The ABCD-GENE score was constructed to identify patients with high platelet reactivity (HPR) after 30 days of clopidogrel treatment. In our study, 1297 eligible patients with acute coronary syndrome (ACS) were included, and 44 (3.4%) major adverse cardiovascular events (MACEs) occurred during the 12-month clopidogrel treatment. The score with a cutoff of ≥ 10 was independently associated with the risk of 5-day HPR (adjusted HR: 1.73, 95% CI: 1.09-2.74, P = 0.020) and MACEs (adjusted HR: 2.25, 95% CI: 1.19-4.25, P = 0.013). The risk of MACEs increased when the multivariable model with the score (≥ 10) plus 5-day HPR was used (adjusted HR: 4.37, 95% CI: 1.90-10.10, P = 0.001). The c-statistic for MACEs was 0.60 when using the score threshold of ≥ 10 and 0.63 when using the model with the score plus 5-day HPR. As a simple tool, the ABCD-GENE score could identify clopidogrel-treated Chinese patients with ACS who are at increased risk of MACEs. The addition of 5-day HPR could slightly improve the diagnostic ability of the score.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Clopidogrel/efectos adversos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/genética , Ticlopidina/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Plaquetas , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
Aim: Growing evidence indicated that CYP2C19 genotypes could only explain a fraction of the pharmacodynamic response to clopidogrel, while a number of clinical factors also have contributing roles. Our objective was to develop a new risk score to improve prognostication of ischemic events in Chinese patients treated with clopidogrel. Methods: A new risk score was developed and internally validated in 445 patients with acute coronary syndrome (ACS) undergoing coronary stenting. The final score was named the GeneFA score based on the inclusion of CYP2C19 genotype, fibrinogen, and age. External validation of the GeneFA score and comparison with the ABCD-GENE score were performed in an independent ACS cohort. Results: Based on the observed frequencies of high platelet reactivity (HRPR) in relation to the GeneFA risk score, a relatively higher clinical HRPR was observed in the upper quintile with a representative score of 3 (52.90%) and 4 (59.10%), whereas it was found less frequently in groups with scores 0 (6.70%), 1 (15.10%), and 2 (16.70%). Participants with a GeneFA score >2 had an increased risk of HRPR (54.3 vs. 14.7%, p < 0.001) and ischemic recurrence (20.7 vs. 5.4%, p < 0.001). The GeneFA score exhibited a better prediction for high HRPR patients as compared to the ABCD-GENE score (p < 0.001). In the validation population, GeneFA illustrated a similarly high prognostic value for HRPR incidence (C-statistic: 0.855 for GeneFA and 0.843 for ABCD-GENE) and ischemic recurrence (C-statistic: 0.726 for GeneFA and 0.724 for ABCD-GENE) on clopidogrel as compared to ABCD-GENE. Conclusion: The GeneFA risk score had a moderate predictive ability for HRPR on clopidogrel for CAD patients in Chinese populations. The predictive value of the GeneFA score was consistent with the ABCD-GENE score for HRPR identification.
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Background: Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear. Methods: To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor. Results: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI. Conclusions: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI. Funding: NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.
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Microbioma Gastrointestinal , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Animales , Disbiosis/tratamiento farmacológico , Humanos , Ratones , Inhibidores de Agregación Plaquetaria/farmacocinética , Inhibidores de Agregación Plaquetaria/uso terapéutico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Ticagrelor/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Recurrent ischemic events in cerebrovascular disease present a difficult problem in clinical practice. The predictive value of cytochrome P450 2C19 (CYP2C19) gene polymorphism and high platelet reactivity for recurrent ischemic events in cerebrovascular disease is not clear. METHODS: A total of 295 patients with acute ischemic cerebrovascular disease admitted to the cerebrovascular disease center of Northern Theater General Hospital between January 1, 2020 and February 2, 2021 were enrolled in this study. Thrombelastography (TEG) was used to detect platelet reactivity and CYP2C19 gene polymorphism. RESULTS: Among the 118 noncarriers, 97 had normal platelet reactivity and 21 had high platelet reactivity. Of the 177 carriers, 120 showed normal platelet reactivity and 57 showed high platelet reactivity. The area under the curve (AUC) of CYP2C19 gene polymorphism in predicting recurrent ischemic events was 0.66. The regression coefficients of hypertension, stroke history, carriers, and high platelet reactivity with recurrent ischemic events were 0.341, 0.402, 0.358, and 0.281, respectively, with significant positive correlation (P<0.05). CONCLUSIONS: Hypertension, stroke history, carriers, and high platelet reactivity are all independent risk factors for recurrent ischemic events. CYP2C19 gene polymorphism and high platelet reactivity can be used as effective predictors of recurrent ischemic events in clinical cerebrovascular disease.
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Citocromo P-450 CYP2C19 , Accidente Cerebrovascular , Tromboelastografía , Clopidogrel , Citocromo P-450 CYP2C19/genética , Humanos , Inhibidores de Agregación Plaquetaria , Polimorfismo Genético/genética , Accidente Cerebrovascular/genética , TiclopidinaRESUMEN
BACKGROUND: High platelet reactivity (HPR) on clopidogrel and chronic kidney disease (CKD) are recognized as potent risk factors for adverse outcomes in patients suffering coronary artery disease (CAD) and undergoing percutaneous coronary intervention (PCI). However, conclusive evidence regarding their reciprocal interaction and the consequent impact on clinical events is still lacking. OBJECTIVES: We performed a metaanalysis with the aim to evaluate the prevalence of HPR in patients with and without CKD and the incidence of major adverse cardiovascular events (MACE) according to the renal and platelet function status in current literature (co-primary endpoints). Secondary endpoints were myocardial infarction (MI), all-cause death, and definite/probable stent thrombosis (ST). METHODS: We searched on PubMed, EMBASE, and Cochrane Library studies investigating CKD and HPR on clopidogrel in patients suffering CAD who underwent PCI and their related outcomes. Overall, 13 studies including 22.464 patients were selected. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using a random-effects model with the Mantel-Haenszel method. RESULTS: Patients with CKD presented significantly higher odds of HPR compared with those without CKD (OR 1.51 [95% CI: 1.29, 1.76]). In patients without CKD, HPR was associated with increased odds of MACE (OR 1.31 [95% CI: 1.01, 1.72]), MI (OR 1.48 [95% CI: 1.17, 1.86]) and definite/probable ST (OR 2.45 [95% CI: 1.08, 5.60]). In patients with CKD, HPR was associated with higher odds of both MACE (OR 1.61 [95% CI: 1.14, 2.27]) and MI (OR 1.69 [95% CI: 1.11, 2.59]), compared to those without HPR. CONCLUSIONS: Our analysis shows that HPR on clopidogrel is more frequent in patients with CKD treated with PCI. Patients with HPR are exposed to a high risk of MACE after PCI, regardless of the renal function status.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Trombosis , Plaquetas , Clopidogrel/efectos adversos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/terapia , Femenino , Humanos , Masculino , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Prevalencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Trombosis/etiología , Resultado del TratamientoRESUMEN
AIMS: High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated. METHODS: Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model. RESULTS: In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, pï¼0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, pï¼0.001). CONCLUSIONS: The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.
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Plaquetas , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Clorhidrato de Prasugrel , Humanos , Plaquetas/efectos de los fármacos , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Citocromo P-450 CYP2C19/genética , Diabetes Mellitus , Hipertensión , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Clorhidrato de Prasugrel/efectos adversos , Estudios ProspectivosRESUMEN
BACKGROUND: Dual antiplatelet therapy with aspirin and P2Y12 receptor inhibitor is an important option for preventing acute stent thrombosis after percutaneous coronary intervention (PCI). CASE SUMMARY: A 72-year-old man was admitted to our hospital with ST-segment elevation myocardial infarction. Emergent coronary angiography identified the occlusion in the proximal left anterior descending artery. This lesion was successfully treated by thrombus aspiration and an everolimus-eluting platinum chromium stent implantation with loading of aspirin 200 mg and prasugrel 20 mg. However, acute closure of the stent occurred 1 h after PCI. P2Y12 reaction units (PRU) measured using VerifyNow assay was 282, suggesting high platelet reactivity on prasugrel. After adding cilostazol 200 mg, recanalization was successfully obtained by thrombus aspiration and ballooning under intra-aortic balloon pump. Thereafter, PRU decreased to 266 at 4 h after PCI, and 49 the next day, implying full inhibition of platelet reactivity on prasugrel. Fortunately, no stent thrombosis has recurred since then. Genotype analysis of cytochrome P450 enzyme (CYP) demonstrated CYP2B6*1/*2 polymorphism leading to impaired metabolism of prasugrel. Based on these findings, acute stent thrombosis in the present case might have been caused by delayed expression of prasugrel effects due to CYP2B6*2 (C64T) polymorphism. DISCUSSION: In cases of stent thrombosis, we should consider the possibility of poor response to P2Y12 receptor inhibitors due to CYP polymorphism. Assessment of platelet aggregation and CYP genotype may be warranted.
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INTRODUCTION: Double antiplatelet therapy (DAPT) has wide inter-individual variabilities in coronary heart disease (CHD) patients' responses, which undermines the prognosis effect in clinical practice. Long noncoding RNAs (lncRNAs) have been reported to be widely existed in platelets, albeit their potential roles in platelet responses to DAPT largely remains in the realm of the unknown. This study aims to screen differentially expressed lncRNAs responsible for high residual platelet reactivities under DAPT. METHODS: We enrolled 144 CHD patients that received DAPT and assigned them to high platelet reactivity (HPR) group and baseline group according to their residual platelet reactivities. Statistical analysis and a series of experiments including microarray analysis, platelet reactivity screening, RNA isolation and lncRNA microarray analysis were explored to the research. RESULTS: We detected a total of 22,424 kinds of co-expressed lncRNAs in three pairs of patients between the HPR and baseline groups. We identified twenty differentially expressed lncRNAs and successfully validated three of them in the 144 patients. Ultimately, the expression of ensemble transcript ENST00000433442 was demonstrated as significantly correlated with high platelet reactivity (OR = 0.487, P = .035) by logistic regression analysis. CONCLUSION: There is a considerable amount of lncRNAs in platelets, and the downregulated expression of ENST00000433442 is an independent risk factor for high residual platelet reactivity in CHD patients under DAPT.
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Plaquetas/metabolismo , Perfilación de la Expresión Génica/métodos , Activación Plaquetaria/genética , ARN Largo no Codificante , Transcriptoma , Biomarcadores , Fraccionamiento Celular , Citocromo P-450 CYP2C19/genética , Femenino , Humanos , Masculino , Variantes Farmacogenómicas , Pruebas de Función Plaquetaria/métodos , Pruebas de Función Plaquetaria/normas , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND AND AIMS: Increased ß-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. PATIENTS AND METHODS: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) ß-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. RESULTS: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with ß-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, ß-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and ß-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and ß-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. CONCLUSIONS: Increased ß-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.
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Péptidos beta-Amiloides/sangre , Plaquetas , Clopidogrel/administración & dosificación , Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Proteínas Mitocondriales/sangre , Revascularización Miocárdica , Activación Plaquetaria/efectos de los fármacos , Anciano , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/terapia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT-guided antiplatelet therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited. METHODS: We analyzed 1,353 consecutive STEMI patients undergoing primary PCI. PFT was performed 72 hr postprocedure using a vasodilator-stimulated phosphoprotein assay. The primary endpoint of major adverse cardio-cerebral events (MACCEs) was defined as a composite of all-cause death, cardiac death, nonfatal myocardial infarction, target vessel revascularization, and ischemic stroke. Patients with high platelet reactivity (HPR) were randomized to receive an intensified antiplatelet strategy by switching from clopidogrel to ticagrelor (HPR switch group) or to continue on clopidogrel (HPR nonswitch group). One-year clinical outcomes were compared among the groups. RESULTS: The baseline clinical characteristics were comparable across all groups (all p > .05). At the 1-year clinical follow-up, the primary endpoint of MACCE was significantly higher in the HPR nonswitch group than in the non-HPR and HPR switch groups (19.49% vs. 10.20% or 8.57%, p < .05), which was mainly caused by higher mortality (14.87% vs. 4.51% or 5.71%, p < .05). Major bleeding events were comparable across the groups. CONCLUSIONS: In STEMI patients with HPR, identified by vasodilator stimulated phosphoprotein (VASP)-determined PFT, switching clopidogrel to ticagrelor could significantly improve 1-year clinical outcomes without increasing the risk of bleeding.
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Plaquetas/efectos de los fármacos , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Pruebas de Función Plaquetaria , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Aspirina/administración & dosificación , Biomarcadores/sangre , Plaquetas/metabolismo , Moléculas de Adhesión Celular/sangre , China , Clopidogrel/administración & dosificación , Sustitución de Medicamentos , Terapia Antiplaquetaria Doble/efectos adversos , Terapia Antiplaquetaria Doble/mortalidad , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Proteínas de Microfilamentos/sangre , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Fosfoproteínas/sangre , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/mortalidad , Ticagrelor/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.
Asunto(s)
Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Anciano , Aspirina/efectos adversos , Clopidogrel/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Trombosis Coronaria/mortalidad , Trombosis Coronaria/prevención & control , Stents Liberadores de Fármacos , Terapia Antiplaquetaria Doble/efectos adversos , Terapia Antiplaquetaria Doble/mortalidad , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Estudios Prospectivos , Sistema de Registros , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Extracranial carotid artery aneurysms (ECAA) are extremely rare, accounting for less than 1% of all peripheral artery aneurysms. The most common presentation is central neurologic dysfunction, typically due to embolization of thrombus from the aneurysm. Historically open surgical intervention is the treatment of choice for symptomatic ECAA. Recent data suggest that endovascular repair is a valuable alternative, with a high procedural success rate and relatively low complication rate. We present a case of an ECAA with symptoms of vision loss, successfully treated by endovascular covered stenting but complicated by late in stent thrombosis and cerebral infarction. The patient was subsequently treated with IV thrombolysis and life-long warfarin. The patient had discrete residual symptoms at follow-up 3 months later.
Asunto(s)
Aneurisma/cirugía , Enfermedades de las Arterias Carótidas/cirugía , Procedimientos Endovasculares/efectos adversos , Oclusión de Injerto Vascular/etiología , Stents/efectos adversos , Trombosis/etiología , Anticoagulantes , Femenino , Oclusión de Injerto Vascular/terapia , Humanos , Persona de Mediana Edad , Terapia Trombolítica , Trombosis/terapia , Warfarina/uso terapéuticoRESUMEN
Studies on antiplatelet effect of ticagrelor/aspirin and clopidogrel/aspirin in patients with acute minor stroke and transient ischemic attack (TIA) stratified by CYP2C19 metabolizer status is limited. We gained data from the Platelet Reactivity In Non-disabling Cerebrovascular Events study. Platelet reactivity was tested at baseline, 2 hours, 24 hours, 7 days and 90 days after initial dose, including high on-treatment platelet reactivity (HOPR), which was defined as P2Y12 reaction unit >208, and percentage inhibition of platelet aggregation (IPA). A total of 365 patients were included. There were 199 (54.5%) individuals classified as carriers of CYP2C19 loss-of-function alleles. For carriers and non-carriers, the proportions of HOPR were significantly lower in those with ticagrelor/aspirin compared with those with clopidogrel/aspirin at 2 hours, 24 hours, 7 days, respectively (all p<0.05). IPA was higher at all time points except at baseline in patients with ticagrelor/aspirin compared with those with clopidogrel/aspirin in both carriers and non-carriers of CYP2C19 lose-of-function alleles (all p<0.05). Our findings showed that ticagrelor/aspirin therapy possessed greater platelet inhibition and more rapid onset in platelet inhibition compared with clopidogrel/aspirin therapy both in carriers and non-carriers of CYP2C19 lose-of-function alleles with acute minor stroke or TIA.