RESUMEN
INTRODUCTION: The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. METHODS: This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (- 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints-the visuospatial/executive domain + 0.04 (p = 0.651), naming domain - 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain - 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain - 0.05 (p = 0.224)-but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level-0-54 mg/dL, 55-69 mg/dL and ≥ 70 mg/dL; p = 0.454-or between alirocumab and evolocumab arms. CONCLUSION: We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. REGISTRATION: ClinicalTtrials.gov Identifier number NCT04319081.
Asunto(s)
Inhibidores de PCSK9 , Proproteína Convertasa 9 , Humanos , LDL-Colesterol , Estudios de Seguimiento , Estudios Prospectivos , Cognición , Anticuerpos Monoclonales/efectos adversosRESUMEN
OBJECTIVE: We designed a clinical study to analyze patterns of adherence to obeticholic acid, factors influencing the adherence and potential correlation with treatment efficacy by using MEMS® cap in practice daily. Method: A multicenter prospective observational study of patients with primary biliary cholangitis. Adherence will be measured by MEMS® cap, pill count, and patient-reported outcomes during 3 months. The quality of life will be self- reported using the Chronic Liver Disease Questionnaire test, European Quality of Life 5-Dimension Questionnaire test and Itch Severity Scale. CONCLUSIONS: We expect to clarify if there is correlation between adherence with treatment efficacy and to identify causes for poor compliance and introduce measures to reduce its prevalence.
OBJETIVO: Diseñamos un estudio clínico para analizar los patrones de adherencia al ácido obeticólico, los factores que influyen en la adherencia y la posible correlación con la eficacia del tratamiento mediante el uso de MEMS® cap en la práctica clínica diaria.Método: Estudio observacional prospectivo multicéntrico de pacientes con colangitis biliar primaria. La adherencia se medirá mediante MEMS® cap, el recuento de comprimidos y se registrarán los resultados comunicados por el paciente durante 3 meses. La calidad de vida será autoinformada utilizando el Cuestionario de Enfermedad Hepática Crónica, el Cuestionario Europeo de Calidad de Vida en cinco dimensiones y la Escala de Intensidad del Picor. CONCLUSIONES: Esperamos identificar si existe una relación entre la adherencia con la efectividad del tratamiento e identificar las causas de la falta de adherencia para poder introducir medidas para reducir su prevalencia.
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Sistemas de Medicación , Calidad de Vida , Ácido Quenodesoxicólico/análogos & derivados , Humanos , Cumplimiento de la Medicación , AutoinformeRESUMEN
INTRODUCTION: Inhaled antibiotics reduce the frequency of exacerbations. The objective was to assess the efficacy of inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis (NCFB) and concomitant chronic bronchial infection (CBI) caused by potentially pathogenic microorganisms (PPM) other than Pseudomonas aeruginosa (PA). MATERIAL AND METHOD: Quasi-experimental study in 21 patients with exacerbations who developed CBI by a PPM other than PA. RESULTS: Bacterial infection was resolved in 85.7% patients. Rehospitalizations, length of hospital stay, moderate exacerbations and blood levels of CRP decreased significantly. In addition, SGRQ questionnaire also decreased more than 4 points in 57.1% of the patients. CONCLUSION: The results suggest that inhaled ceftazidime in NCFB unrelated to PA is a plausible alternative to the standard therapies used in clinical practice.
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Bronquiectasia , Bronquitis Crónica , Fibrosis Quística , Infecciones por Pseudomonas , Humanos , Pseudomonas aeruginosa , Ceftazidima/uso terapéutico , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Administración por Inhalación , Bronquiectasia/complicaciones , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Antibacterianos/uso terapéutico , FibrosisRESUMEN
OBJECTIVES: MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control; (2) descriptive analysis; (3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab; (4) communicate PCSK9i safety. MATERIAL AND METHODS: It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time. RESULTS: 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148mg/dL and the follow-up value was 71mg/dL. The baseline value of patients treated with alirocumab (N=43) was 144mg/dL and 73mg/dL in the follow-up. With evolocumab (N=46) was 151mg/dL in basaline and 69mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70mg/dL in six month time; 19.4% between 69mg/dl and 55mg/dL and 37.5% <55mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N=2), myalgias (N=1), flu-like symptoms (N=1) and neurocognitive worsening (N=1). CONCLUSIONS: (1) Despite the number of prescriptions was reduced because of the pandemic, the lipid control was not affected. (2) Half of the patients treated with PSCK9i is due to statins intolerance and the 86% is for secondary prevention. (2) The reduction results were similar to pivotal clinical trials. Despite this, 39% of the total of the patients and 60% of patients with dual teraphy did not reach the goal of ESC/EAS guidelines (<55mg/dL and/or reduction>50%). There were not significant differences between evolocumab and alirocumab: 51.21% vs 51.05% (P=.972). (3) There were not any adverse events of special interest. The possible neurocognitive worsening will be studied as the primary endpoint once the MEMOGAL study has been completed.
Asunto(s)
Anticolesterolemiantes , Tratamiento Farmacológico de COVID-19 , COVID-19 , Inhibidores de PCSK9 , Anticolesterolemiantes/efectos adversos , COVID-19/epidemiología , LDL-Colesterol , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de PCSK9/efectos adversos , Pandemias , Proproteína Convertasa 9 , Estudios ProspectivosRESUMEN
OBJECTIVE: PCSK9 inhibitors have been shown to reduce LDLc by up to about 60% and 85% when used with high doses of statins and ezetimibe (2019 ESC/EAS Guidelines). These therapies may lead to very low levels of LDLc and have been associated with possible cognitive deterioration. No significant differences were found in the only specific study (EBBINGHAUS). The objective is to prospectively evaluate cognitive deterioration and its repercussion on quality of life and changes in LDLc in patients starting treatment with PCKS9 inhibitors. METHOD: It is a postauthorization, multicentre, non-randomized, prospective study. Patients starting treatment for the first time with PCSK9 inhibitors will be recruited in 11 Galician Hospitals over a period of 12 months and with 24 months of follow-up. The primary outcome will be to evaluate changes in cognitive function using the Montreal Cognitive Assessment (MOCA) questionnaire. The secondary outcome will be to evaluate changes in quality of life using the EuroQol-5D. Changes in LDLc will be assessed. The sample size will be 275 patients, taking into account a loss to follow-up of no more than 10%. The primary outcome will be studied through the dichotomous variable cognitive deterioration (0/1). Cognitive changes over the follow-up period will be analysed using the McNemar test. In addition, an analytical approach using logistic regression will be followed to identify patients at risk of cognitive deterioration. As a result, this analysis will obtain a frequency measurement: the odds ratio (OR). The specific objectives will be studied using bivariate analysis. Continuous contrast variables will be studied using the t-test or ANOVA and categorical variables will be studied using the chi- square test. CONCLUSIONS: The MEMOGAL study will provide information on safety in terms of cognitive deterioration in patients starting treatment with PCSK9 inhibitors.
Objetivo: Los inhibidores de proproteína convertasa subtilisina/kexina de tipo 9 (PCSK9) han demostrado reducir hasta un 60% el colesterol transportado por lipoproteínas de baja densidad (c-LDL) y hasta el 85% asociado a estatinas de alta intensidad y ezetimibe (2019 ESC/EAS Guidelines). Estas terapias pueden dar lugar a muy bajos niveles de c-LDL y se ha especulado sobre su posible relación con deterioro cognitivo. En el único estudio específico, EBBINGHAUS, no se encontraron diferencias significativas. El objetivo es evaluar prospectivamente el deterioro cognitivo y la repercusión en términos de calidad de vida y variaciones de c-LDL en pacientes que inician tratamiento con inhibidores de PCSK9. Método: Se trata de un estudio postautorización, multicéntrico, no aleatorizado de seguimiento prospectivo. Se reclutarán pacientes que inicien tratamiento por primera vez con iPCSK9 en 11 hospitales gallegos durante un periodo de 12 meses y un seguimiento de 24 meses. El endpoint primario será evaluar los cambios en la función cognitiva a través del cuestionario Montreal Cognitive Assessment (MOCA), y como endpoints secundarios se valorarán cambios en la calidad de vida a través del EuroQol5D y variación de los niveles de LDL. El tamaño muestral, teniendo en cuenta un porcentaje de pérdidas no superior al 10%, será de 275 individuos. El objetivo general se estudiará a través de la variable dicotómica deterioro cognitivo (0/1). El estudio del deterioro cognitivo a lo largo del seguimiento se realizará con el test McNemar. Además, se pretende realizar un planteamiento analítico con una regresión logística que explore si existe algún perfil de paciente con riesgo de sufrir deterioro cognitivo. Este análisis obtendrá como resultado una medida de frecuencia, la odds ratio (OR). Los objetivos específicos se estudiarán planteando análisis bivariados. Para las variables de contraste continuas se empleará el test T o el ANOVA, si las variables son de naturaleza categórica se aplicará el test de chi cuadrado.Conclusiones: El estudio MEMOGAL intentará aportar información sobre la seguridad en términos de deterioro cognitivo en pacientes que inicien tratamiento con inhibidores de PCSK9 (real-world evidence).