RESUMEN
Pembrolizumab is a humanized monoclonal antibody against PD-1 capable of enhancing antitumor immune activity. The KEYNOTE-001 study showed that pembrolizumab has activity in advanced non-small-cell lung cancer patients and identified programmed death ligand 1 (PD-L1) as a companion test to select patients most likely to benefit from pembrolizumab. Five randomized clinical trials showed the efficacy of pembrolizumab in non-small-cell lung cancer: in second-line setting PD-L1 ≥1% (KEYNOTE-010), in first-line setting PD-L1 ≥50% (KEYNOTE-024 and KEYNOTE-042) and in first-line setting in combination with platinum doublets, any expression of PD-L1 (KEYNOTE-189 and KEYNOTE-407). Future challenges are the identification of the role of pembrolizumab in adjuvant, neoadjuvant, locally advanced disease or oncogene-addicted patients, in combination with radiotherapy or other biological agents.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptores de Estrógenos/metabolismo , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Animales , Anticuerpos Monoclonales Humanizados/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Docetaxel/administración & dosificación , Evaluación de Medicamentos , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Ratones , Nivolumab/administración & dosificación , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/patología , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization. METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists). RESULTS: We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17-4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20-11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52-1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59-1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62-2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63-2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99-5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28-2.29], p = 0.68). CONCLUSION: In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.
Asunto(s)
Plaquetas/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina/administración & dosificación , Adenosina/análogos & derivados , Anciano , Clopidogrel , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Intervención Coronaria Percutánea/métodos , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria/métodos , Factores de Riesgo , Caracteres Sexuales , Ticagrelor , Ticlopidina/administración & dosificación , Ticlopidina/análogos & derivadosRESUMEN
Glycoprotein IIb/IIIa (GP IIb/IIIa) is a key receptor for platelet aggregation and adhesion. We investigated whether a single-nucleotide polymorphism of GP IIIa subunit (Leu33Pro-PlA(1)/PlA(2) allele) is associated with the extent of coronary artery disease (CAD) in a consecutive cohort of 1518 patients undergoing coronary angiography. Significant CAD was defined as at least a stenosis >50% and severe CAD as left main disease and/or trivessel disease. Additionally, carotid intima-media thickness (cIMT) was evaluated in 339 patients. The PlA(2) allele was observed in 458 (30.2%) patients and associated with hypercholesterolemia (P = .03). No difference was observed in the prevalence of CAD (72.6% vs 70.1%, P = .29; adjusted odds ratio, OR [95% confidence interval, CI] = 0.85 [0.67-1.08], P = .19) and severe CAD (27.5% vs 26.5%, adjusted OR [95% CI] = 0.93 [0.72-1.19], P = .55). Furthermore, Leu33Pro polymorphism did not affect cIMT and the prevalence of carotid plaques. Therefore, this polymorphism cannot be regarded as a risk factor for coronary or carotid atherosclerosis.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Estenosis Coronaria/genética , Integrina beta3/genética , Polimorfismo de Nucleótido Simple , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/genética , Grosor Intima-Media Carotídeo , Distribución de Chi-Cuadrado , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/epidemiología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Italia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Contrast-induced nephropathy (CIN) is a common complication in patients with impaired kidney function undergoing coronary angiography/angioplasty. We evaluated whether elevated homocysteine (known to be associated with free radical generation and oxidative stress) increases the risk of CIN. Patients (n = 876) with creatinine clearance <60 mL/min undergoing coronary angiography or percutaneous coronary intervention (PCI) were divided into tertiles of homocysteine levels. Contrast-induced nephropathy was defined as ≥0.5 mg/dL or ≥25% creatinine increase 24 to 48 hours post-PCI. A significant relationship was observed between homocysteine levels and the risk of CIN (P = .033), confirmed after correction for baseline confounding factors, adjusted odds ratio, OR (95% confidence interval, [CI]) = 1.68 (1.09-2.59), P = .019. This association was also significant applying the new definition of contrast-induced acute kidney injury (11.9% in group 1, 10.4% in group 2, and 22.8% in group 3; P < .001), adjusted OR (95% CI) = 1.96 (1.3-2.95), P = .001. Future studies are needed to confirm our findings and to define the role of homocysteine in CIN.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Medios de Contraste/efectos adversos , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Homocisteína/sangre , Hiperhomocisteinemia/complicaciones , Riñón/efectos de los fármacos , Intervención Coronaria Percutánea/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/diagnóstico , Riñón/fisiopatología , Modelos Logísticos , Masculino , Oportunidad Relativa , Sistema de Registros , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Our goal was to estimate the role of high-density lipoprotein cholesterol (HDL-C) in predicting the prevalence and extent of coronary artery disease (CAD) in 3280 patients undergoing coronary angiography. Predictors of lower HDL levels (<32 mg/dL) were male gender (P < .001), diabetes mellitus (P = .03), renal failure (P = .01), higher low-density lipoprotein and total cholesterol (P < .001, respectively), triglycerides (P < .001), and white blood cells (P < .001), aging (P < .001), previous myocardial infarction (P = .02) and hemoglobin (P < .001), treatment with angiotensin-receptor blockers (P < .001), and statins (P = .002). The HDL-C levels were significantly inversely associated with prevalence of CAD (P < .001, adjusted odds ratio [OR] [95% confidence interval, CI] = 1.35 [1.25-1.45], P < .001), and HDL-C <44 mg/dL was best the predictive value of the risk of CAD, (adjusted OR [95%CI] = 1.61 [1.24-2.1], P < .001). We found significant association between HDL-C and the risk of CAD; a value <44 mg/dL was the best cutoff in the prediction of CAD.