RESUMEN
BACKGROUND: Sickle cell disease (SCD) is the most common hemoglobinopathy, occurring worldwide, and vaso-occlusive events (VOEs) are its paramount, hallmark clinical manifestation. Evidence exists that platelets play an important role in generating VOEs. OBJECTIVE: To assess the clinical benefits and harms of antiplatelet agents for preventing VOEs in patients with SCD. METHODS: We conducted searches of the Cochrane Central Register of Controlled Trials (CENTRAL; up to 2018, issue 3 of 12), PubMed/MEDLINE (up to April 20, 2018), and the Excerpta Medica database (EMBASE; from 1980 to week 16 of 2018). We also searched the Latin American and Caribbean Health Sciences Literature (LILACS) database, the US Food and Drug Administration (FDA) website, the European Medicines Agency (EMA) website, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and www.ClinicalTrials.gov. We checked the bibliographies of included studies and any relevant systematic reviews. Our systematic review included randomized clinical trials (RCTs) conducted in people who had SCD without VOEs at trial entry. Eligible trials compared a single or combination treatment regimen (with each treatment classified as a conventional or nonconventional antiplatelet agent) with conventional care, placebo, or another regimen. No restrictions were placed on the route of administration, dose, frequency, or duration of treatment. We selected RCTs, assessed the risk for bias, and extracted data in a duplicate and independent fashion. We estimated risk ratios for dichotomous outcomes and mean differences for continuous outcomes. We also subjected our analyses to a random-effects model, and Trial Sequential Analysis (TSA) was used. We used the grading of recommendations, assessment, development, and evaluation (GRADE) approach to assess the overall quality of data for each individual outcome. RESULTS: We identified 5 RCTs (N=747) that met our criteria. Of these, 4 trials were multicenter and multinational. The trials included patients of all ages and assessed prasugrel, ticagrelor, crizanlizumab, and aspirin vs either placebo or no intervention. The most frequent route of administration was oral. The trials were small and carried a high risk for bias, given that pharmaceutical companies sponsored 4 of them. None of the trials reported information on quality of life. No meta-analysis was performed owing to heterogeneity in the ages of the participants and in the interventions. No single trial showed evidence of certainty regarding all-cause mortality. One trial showed uncertainty in comparing prasugrel vs placebo for preventing VOEs in patients younger than 18 years (relative risk [RR], 0.92; 95% CI, 0.80 to 1.06; low quality of evidence). TSA for this outcome suggested that a new trial should be conducted. One trial found a difference in the size effect of uncomplicated VOEs, favoring high-dose crizanlizumab vs placebo (mean difference, -1.50; 95% CI, -2.61 to -0.39; very low quality of evidence). No difference in VOEs was found in studies that compared either ticagrelor in children or prasugrel in adults vs placebo. The overall incidence of harms in any intervention did not differ from that in the control. CONCLUSIONS: The current evidence does not support or reject the use of any antiplatelet agent for preventing VOEs in people with SCD. This conclusion was based on small RCTs that carried a high risk for bias. No conclusive evidence exists regarding relevant clinical outcomes because the evidence is limited and of very low quality.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Inhibidores de Agregación Plaquetaria/uso terapéutico , Enfermedades Vasculares/prevención & control , Adulto , Anemia de Células Falciformes/fisiopatología , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Hemorragia/inducido químicamente , Humanos , Mortalidad , Estudios Multicéntricos como Asunto , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/clasificación , Clorhidrato de Prasugrel/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ticagrelor/efectos adversos , Ticagrelor/uso terapéutico , Resultado del Tratamiento , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatologíaRESUMEN
BACKGROUND: A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. METHODS: We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine-Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). RESULTS: The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92-2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). CONCLUSION: Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.
Asunto(s)
Síndrome Coronario Agudo/cirugía , Clopidogrel/efectos adversos , Técnicas de Apoyo para la Decisión , Hemorragias Intracraneales/inducido químicamente , Alta del Paciente , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/efectos adversos , Síndrome Coronario Agudo/diagnóstico , Factores de Edad , Anciano , Asia/epidemiología , Brasil/epidemiología , Canadá/epidemiología , Transfusión de Eritrocitos , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/terapia , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Intervención Coronaria Percutánea/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Valor Predictivo de las Pruebas , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Ticagrelor/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease's complex pathophysiology. Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD. Expert opinion: Prasugrel administration in SCD appears to be well tolerated and safe. However, although this drug modestly inhibits platelet activity in these patients, administration of prasugrel to a large group of children and adolescents for up to 24 months failed to convincingly reduce vaso-occlusive complications. Speculatively, prasugrel may be of occasional use for off-license purposes in patients unable or unwilling to take hydroxyurea (particularly in 12-17-year olds). Although there is currently no prospect of prasugrel being licensed for use in SCD, the success of on-going trials of other antiplatelet agents in SCD might lead to further trials of prasugrel in SCD.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Adolescente , Adulto , Anemia de Células Falciformes/fisiopatología , Animales , Niño , Humanos , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacología , Clorhidrato de Prasugrel/efectos adversos , Clorhidrato de Prasugrel/farmacología , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/farmacología , Antagonistas del Receptor Purinérgico P2Y/uso terapéuticoRESUMEN
OBJETIVES: The main objective of the present randomized pilot study was to explore the effects of upstream prasugrel or ticagrelor or clopidogrel for patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Administration of clopidogrel "as soon as possible" has been advocated for STEMI. Pretreatment with prasugrel and ticagrelor may improve reperfusion. Currently, the angiographic effects of upstream administration of these agents are poorly understood. METHODS: A total of 132 patients with STEMI within the first 12 hr of chest pain referred to primary angioplasty were randomized to upstream clopidogrel (600 mg), prasugrel (60 mg), or ticagrelor (180 mg) while still in the emergency room. All patients underwent protocol-mandated thrombus aspiration. RESULTS: Macroscopic thrombus material was retrieved in 79.5% of the clopidogrel group, 65.9% of the prasugrel group, and 54.3% of the ticagrelor group (P = 0.041). At baseline angiography, large thrombus burden was 97.7% vs. 87.8% vs. 80.4% in the clopidogrel, prasugrel, and ticagrelor groups, respectively (P = 0.036). Also, at baseline, 97.7% presented with an occluded target vessel in the clopidogrel group, 87.8% in the prasugrel group and 78.3% in the ticagrelor group (P = 0.019). At the end of the procedure, the percentages of patients with combined TIMI grade III flow and myocardial blush grade III were 52.3% for clopidogrel, 80.5% for prasugrel, and 67.4% for ticagrelor (P = 0.022). CONCLUSIONS: In patients with STEMI undergoing primary PCI within 12 hr, upstream clopidogrel, prasugrel or ticagrelor have varying angiographic findings, with a trend toward better results for the latter two agents. © 2015 Wiley Periodicals, Inc.
Asunto(s)
Adenosina/análogos & derivados , Angioplastia Coronaria con Balón , Angiografía Coronaria , Inhibidores de Agregación Plaquetaria/administración & dosificación , Clorhidrato de Prasugrel/administración & dosificación , Infarto del Miocardio con Elevación del ST/terapia , Ticlopidina/análogos & derivados , Adenosina/administración & dosificación , Adenosina/efectos adversos , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Brasil , Clopidogrel , Esquema de Medicación , Servicios Médicos de Urgencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Trombectomía , Ticagrelor , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
Greater antithrombotic potency new antiplatelet agents have been added such as prasugrel (PR) and ticagrelor to the traditional use of clopidogrel (CL) in the treatment of acute coronary syndrome (ACS). This study was aimed at comparing the incidence of long term ischemic and hemorrhagic events in patients treated with CL or PR during hospitalization. Retrospective ACS data base analysis performed by our cardiology service was completed prospectively. There were consecutively included all patients with percutaneous coronary intervention (PCI) during hospitalization due to ACS from December 2011 thru December 2012. A total of 398 ACS patients who underwent PCI with stent implantation were recruited. No differences in cardiovascular related deaths were observed in both groups (PR 2.9% vs. CL 2.5%, p=0.48). PR group showed less re-infraction (1.9% vs. 6.8%, p=0.01) with more total bleedings (18.5% vs. 8.5%, p=0.001) and minor bleedings (12.4% vs. 3.4%, p<0.001) with no differences in major and life threatening bleedings (p=ns). Multivariate analysis showed that independent predictors of cardiovascular mortality were age (OR 1.08, CI 95% 1.02-1.16) and renal failure (OR 6.98, CI 95% 1.23-39.71). Independent predictors for total bleeding were age (OR 1.06, CI 95% 1.02-1.09),ST segment elevation myocardial infarction (OR 1.99, CI 95% 1.05-3.79), renal failure (OR 3.32, CI 95% 1.62-6.78) and prasugrel use (OR 3.97, CI 95% 1.87-8.41). Use of prasugrel, in the ACS that requires PCI with stent, is associated with a lower myocardial infarction a year after follow-up, and it also leads to an increase of milder hemorrhage. No significant differences were observed in the cardiovascular mortality of both groups.
Asunto(s)
Síndrome Coronario Agudo/terapia , Angioplastia/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Stents , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/mortalidad , Angioplastia/efectos adversos , Clopidogrel , Femenino , Hemorragia/prevención & control , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Estudios Retrospectivos , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
Al uso del clopidogrel se han agregado nuevos antiagregantes como prasugrel y ticagrelor. El objetivo de este estudio fue comparar la incidencia de eventos isquémicos y hemorrágicos en pacientes que han recibido clopidogrel o prasugrel.Se incluyeron de manera consecutiva todos los pacientes con angioplastia durante la internación por síndrome coronario agudo entre diciembre 2011 y diciembre 2012.Fueron incluidos 398 pacientes. No se observaron diferencias en la mortalidad de causa cardiovascular (clopidogrel 2.5% vs. prasugrel 2.9%, p = 0.48). El grupo prasugrel presentó una reducción en la tasa de infarto (1.9% vs. 6.8%, p = 0.01) con sangrado totales (18.5% vs. 8.5%, p = 0.001) a expensas de sangrados menores (12.4% vs. 3.4%, p < 0.001), sin diferencia en sangrados mayores (p = 0.27) y sangrados con peligro de vida (p =.0.20). Por análisis multivariado los predictores independientes de mortalidad cardiovascular fueron edad (odds ratio 1.08, intervalo de confianza, IC, 95% 1.02-1.16, p = 0.02) insuficiencia renal (odds ratio 6.98, IC 95% 1.23-39.71, p < 0.0001). En cuanto al sangrado total se identificaron la edad (odds ratio 1.06, IC 95% 1.02-1.09, p = 0.002), elevación del segmento ST (odds ratio 1.99, IC 95% 1.05-3.79, p = 0.02), insuficiencia renal (odds ratio 3.32, IC 95% 1.62-6.78, p = 0.002) y utilización de prasugrel (odds ratio 3.97, IC 95% 1.87-8.41, p < 0.0001). La utilización de prasugrel se asocia a una menor tasa de infarto agudo de miocardio al año de seguimiento, con incremento de hemorragias menores. No se observaron diferencias significativas en la mortalidad cardiovascular entre ambos grupos.
Greater antithrombotic potency new antiplatelet agents have been added such as prasugrel (PR) and ticagrelor to the traditional use of clopidogrel (CL) in the treatment of acute coronary syndrome (ACS). This study was aimed at comparing the incidence of long term ischemic and hemorrhagic events in patients treated with CL or PR during hospitalization. Retrospective ACS data base analysis performed by our cardiology service was completed prospectively. There were consecutively included all patients with percutaneous coronary intervention (PCI) during hospitalization due to ACS from December 2011 thru December 2012. A total of 398 ACS patients who underwent PCI with stent implantation were recruited. No differences in cardiovascular related deaths were observed in both groups (PR 2.9% vs. CL 2.5%, p = 0.48). PR group showed less re-infraction (1.9% vs. 6.8%, p = 0.01) with more total bleedings (18.5% vs. 8.5%, p = 0.001) and minor bleedings (12.4% vs. 3.4%, p < 0.001) with no differences in major and life threatening bleedings (p = ns). Multivariate analysis showed that independent predictors of cardiovascular mortality were age (OR 1.08, CI 95% 1.02-1.16) and renal failure (OR 6.98, CI 95% 1.23-39.71). Independent predictors for total bleeding were age (OR 1.06, CI 95% 1.02-1.09),ST segment elevation myocardial infarction (OR 1.99, CI 95% 1.05-3.79), renal failure (OR 3.32, CI 95% 1.62-6.78) and prasugrel use (OR 3.97, CI 95% 1.87-8.41). Use of prasugrel, in the ACS that requires PCI with stent, is associated with a lower myocardial infarction a year after follow-up, and it also leads to an increase of milder hemorrhage. No significant differences were observed in the cardiovascular mortality of both groups.