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Browsing by Subject "Percutaneous Coronary Intervention/adverse effects"
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Item CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.(Journal of the American Heart Association, 2022-02-15) Beitelshees, Amber L.; Thomas, Cameron D.; Empey, Philip E.; Stouffer, George A.; Angiolillo, Dominick J.; Franchi, Francesco; Tuteja, Sony; Limdi, Nita A.; Lee, James C.; Duarte, Julio D.; Kreutz, Rolf P.; Skaar, Todd C.; Coons, James C.; Giri, Jay; McDonough, Caitrin W.; Rowland, Rachel; Stevenson, James M.; Thai, Thuy; Vesely, Mark R.; Wellen, Jacob T.; Johnson, Julie A.; Winterstein, Almut G.; Cavallari, Larisa H.; Lee, Craig R.Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life-threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.Item MicroRNA sequencing in patients with coronary artery disease - considerations for use as biomarker for thrombotic risk.(Wiley, 2022-08) Onuoha, Chimnonso P.; Ipe, Joseph; Simpson, Edward; Liu, Yunlong; Skaar, Todd C.; Kreutz, Rolf P.MicroRNAs (miRNAs) are small RNAs integral in the regulation of gene expression. Analysis of circulating miRNA levels may identify patients with coronary artery disease (CAD) at risk for recurrent myocardial infarction (MI) after percutaneous coronary interventions (PCIs). Subjects with CAD were selected from the GENCATH cardiac catheterization biobank. Subjects with recurrent MI after PCI were compared with those without recurrent MI during follow-up in the initial (n = 48) and replication cohort (n = 67). Next generation MiRNA sequencing was performed on plasma samples and whole blood samples fixed with PAXGENE tubes upon collection. Overall, 164 miRNAs derived from whole blood were differentially expressed in the replication cohort between subjects with and without recurrent MI events (p < 0.05), with 69 remaining significant after false-discovery rate (FDR) correction. None of the miRNAs in plasma was significantly different by FDR among subjects with and without MI. Overall, correlation between direction of effects between plasma and whole blood assays was variable, and only two miRNAs were concordant and significant in both. Associations of miRNA with vascular disease, MI, and thrombosis were further explored. MiRNA profiling has potential as the future biomarker for disease prognosis and treatment response marker in secondary treatment of patients with CAD after PCI. Whole blood may be the preferred sample source as compared to plasma.