RESUMEN
PURPOSE: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. METHODS: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. RESULTS: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. CONCLUSIONS: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. CLINICAL TRIAL REGISTRATION: NCT02101437.
Asunto(s)
Aspirina/uso terapéutico , Plaquetas/efectos de los fármacos , Enfermedad de la Arteria Coronaria/terapia , Resistencia a Medicamentos , MicroARNs/sangre , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Anciano , Aspirina/efectos adversos , Plaquetas/metabolismo , Cilostazol/uso terapéutico , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/genética , Resistencia a Medicamentos/genética , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Método Simple Ciego , Stents , Taiwán , Ticagrelor/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Current treatment guidelines do not recommend different antiplatelet treatments for patients in different coronary risk categories; nor do they consider ethnic differences in responses to individual drugs. OBJECTIVES: We performed a prospective, single-blind, randomized, comparative study of Taiwanese patients with stable angina and scheduled stent implantation for intermediate-to-highly complex coronary lesions and compared the platelet reactivity unit (PRU) levels and 24-month outcomes of groups receiving three different antiplatelet treatments. METHODS: Patients (N = 334) were randomized into three treatment groups (aspirin + clopidogrel, aspirin + ticagrelor, or aspirin + clopidogrel + cilostazol) for 6 months of treatment and were then switched to aspirin only. PRU levels were determined 24 h, 7 days, and 1 month after stent implantation. Clinical outcomes and adverse events were recorded over 24 months. RESULTS: Clopidogrel treatment reached full effect after 1 month. Ticagrelor decreased PRU levels more than did clopidogrel but often to levels that increased the risk of hemorrhage. The addition of cilostazol to clopidogrel decreased PRU levels earlier and more strongly than clopidogrel alone but not as strongly as did ticagrelor. Ticagrelor treatment caused fewer major adverse cardiovascular events (MACEs) and more episodes of minor bleeding than the other two treatments. CONCLUSIONS: Clopidogrel appears safer than ticagrelor in Taiwanese patients with stable angina after stent implantation for intermediate-to-highly complex coronary lesions. The addition of cilostazol to clopidogrel may provide a more rapid decrease in PRU to therapeutic levels without increasing the risk of hemorrhage. CLINICAL TRIAL REGISTRATION NUMBER: NCT02101411.
Asunto(s)
Aspirina/uso terapéutico , Plaquetas/efectos de los fármacos , Cilostazol/uso terapéutico , Diaminas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tiazoles/uso terapéutico , Ticagrelor/uso terapéutico , Anciano , Clopidogrel/uso terapéutico , Femenino , Hemorragia/tratamiento farmacológico , Humanos , Masculino , Intervención Coronaria Percutánea/métodos , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria/métodos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Método Simple Ciego , TaiwánRESUMEN
OBJECTIVES: Toll-like receptors (TLRs) are molecules conserved in evolution for detecting pathogen invasions and tissue damage and are involved in atherogenesis. This study explores the mRNA expression of TLRs and their probable role in further disease occurrence among ischemic stroke patients. DESIGN AND METHODS: A total of 89 ischemic stroke patients and 166 controls were recruited for this study. Total RNA was extracted and mRNA was reverse-transcribed to cDNA and was analyzed for TLRs and interleukin 8 (IL8). RESULTS: The TLR4 mRNA expression level is significantly higher in the stroke group. Conversely, IL-8 mRNA levels decreased significantly in the patient group. CONCLUSION: Our results suggest that TLR4 overexpression in mRNA levels is observed in stroke patients, which might account for the probable inflammatory injury before or after stroke. A reduction of IL-8 expression could result from the downregulatory effects of aspirin.