RESUMEN

RESUMEN Introducción: el modelo SMART-REACH predice el riesgo de eventos cardiovasculares recurrentes. Objetivos: los objetivos de este estudio fueron: a) evaluar el riesgo residual en una población en prevención secundaria y niveles de colesterol asociado a lipoproteínas de baja densidad (C-LDL) fuera de meta; b) mediante un modelo de simulación, determinar el impacto de optimizar las terapias hipolipemiantes en términos de reducción del riesgo residual. Material y métodos: estudio transversal, descriptivo y multicéntrico. Se incluyeron consecutivamente pacientes con antecedentes cardiovasculares y un C-LDL mayor o igual que 55 mg/dL. El riesgo de eventos recurrentes (infarto agudo de miocardio, accidente cerebrovascular o muerte vascular) a 10 años y a lo largo de la vida se estimó utilizando el modelo SMART-REACH. Mediante una simulación, se optimizó el tratamiento hipolipemiante de cada paciente (utilizando estatinas, ezetimibe o inhibidores de proproteína convertasa subtilisina kexina tipo 9 [iPCSK9]), se estimó el descenso del C-LDL, se verificó el alcance del objetivo lipídico y se calculó la reducción del riesgo cardiovascular y el número necesario a tratar (NNT) correspondiente. Resultados: se incluyeron 187 pacientes (edad media 67,9 ± 9,3 años, 72,7% hombres). Los riesgos residuales calculados a 10 años y a lo largo de la vida fueron 37,1 ± 14,7% y 60,3 ± 10,7%, respectivamente. Globalmente, se pudo optimizar una sola estrategia farmacológica con estatinas, ezetimibe o un iPCSK9 en el 38,5%, el 11,5% y el 5,5% de la población, respectivamente. La optimización basada en dos tratamientos se realizó en el 27,5% (estatinas + ezetimibe), el 7,7% (estatinas + iPCSK9) y el 1,1% (ezetimibe + iPCSK9) de los casos. En 15 pacientes se optimizó el tratamiento considerando los tres fármacos. El 53,9% y el 62,9% de las acciones para optimizar el tratamiento mostraron un NNT menor que 30 para evitar un evento a 10 años o a lo largo de la vida, respectivamente. Conclusión: en este estudio, los pacientes con antecedentes cardiovasculares que no alcanzan la meta de C-LDL mostraron un riesgo residual considerable. La simulación mostró un importante margen para optimizar el tratamiento, con un impacto notable en el riesgo residual.

ABSTRACT Background: The SMART-REACH model predicts the risk or recurrent cardiovascular events. Objectives: The objectives of this study were: a) to evaluate the residual cardiovascular risk in a secondary prevention population with LDL-C levels above the recommended goal, using a simulation model; and b) to determine the impact of optimizing lipid-lowering therapies in terms of residual cardiovascular risk reduction. Methods: We conducted a cross-sectional, descriptive and multicenter study. Patient with a history of cardiovascular disease and a LDL-C ≥55 mg/dL were consecutively included. The 10-year and lifetime risk of recurrent events (myocardial infarction, stroke, or vascular death) were estimated using the SMART-REACH model. By means of a simulation, lipid-lowering treatment was optimized for each patient [using statins, ezetimibe and/or PCSK9 (PCSK9) inhibitors], with estimation of LDL-C reduction, checking if lipid-lowering goal was achieved and calculating the reduction in cardiovascular risk and the corresponding number needed to treat (NNT). Results: The cohort was made up of 187 patients; mean age was 67.9 ± 9.3 years and 72.7% were men. The calculated 10-year and lifetime residual risks were 37.1 ± 14.7% and 60.3 ± 10.7%, respectively. Overall, treatment was optimized with a single pharmacological strategy with statins, ezetimibe or PCSK9 inhibitor in 38.5%, 11.5% and 5.5% of the population, respectively. Optimization based on two treatments was performed in 27.5% (statins + ezetimibe), 7.7% (statins + PCSK9 inhibitor) and 1.1% (ezetimibe + PCSK9 inhibitor) of the cases. In 15 patients, treatment was optimized when the three drugs (statins + ezetimibe + PCSK9 inhibitor) were considered. Overall, 53.9% and 62.9% of the actions implemented to optimize treatment showed a 10-year or lifetime NNT < 30 to prevent an event, respectively. Conclusion: In this study, patients with a history of cardiovascular disease who do not reach LDL-C goal showed significant residual cardiovascular risk. The simulation model showed a significant margin for optimizing treatment, with a marked reduction in residual cardiovascular risk.

RESUMEN

Objetivos: El estudio MEMOGAL (NCT04319081) está dirigido a evaluar cambios en la función cognitiva en pacientes tratados con inhibidores de la PCSK9 (iPCSK9). Se realiza primer análisis: 1) discutir el papel de los farmacéuticos hospitalarios durante de la pandemia, así como evaluar el impacto de la misma en el control lipídico; 2) análisis descriptivo; 3) eficacia en reducción de colesterol-LDL (c-LDL) de alirocumab y evolocumab; y 4) reportar seguridad de los iPCSK9. Material y métodos: Se trata de un análisis prospectivo en vida real de pacientes tratados por primera vez con iPCSK9 en la práctica clínica habitual e incluidos en su primera dispensación en las consultas de farmacia de 12 hospitales de Galicia desde mayo de 2020-abril de 2021. Los valores basales de c-LDL son los previos al inicio del tratamiento con iPCSK9 y como seguimiento los valores a los 6 meses. Resultados: Se incluyeron 89 pacientes. El 86,5% con enfermedad cardiovascular y un 53,9% intolerancia a las estatinas. Un 78,8% de los pacientes fueron tratados con estatinas de alta intensidad. Las estatinas más usadas fueron rosuvastatina (34,1%) y atorvastatina (20,5%). El nivel basal de c-LDL fue 148mg/dl y de 71mg/dl al seguimiento. Los pacientes tratados con alirocumab (n=43) presentaban valores basales de 144mg/dl y de 73mg/dl al seguimiento y con evolocumab (n=46) de 151mg/dl basal y 69mg/dl al seguimiento. La reducción de c-LDL fue para evolocumab 51,21% y alirocumab 51,05%. El 43,1% presentaba a los 6 meses valores>70mg/dl, el 19,4% entre 55 y 69mg/dl y el 37,5%<55mg/dl. Los pacientes que obtuvieron una reducción>50% de c-LDL fueron el 58,3%. Los eventos adversos presentados fueron: reacción en el lugar de inyección (n=2), mialgias (n=1), síntomas pseudogripales (n=1) y deterioro neurocognitivo (n=1).(AU)

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).(AU)

Asunto(s)

RESUMEN

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)

RESUMEN

RESUMEN Los inhibidores de la proproteína convertasa subtilisina kexina tipo 9 (iPCSK9) representan un nuevo grupo de fármacos hipolipemiantes, que han generado un cambio sustancial en el manejo clínico de los lípidos. En pocos años, una gran cantidad de estudios han evaluado la eficacia antilipídica y la seguridad de estos fármacos. Más recientemente, grandes ensayos clínicos aleatorizados demostraron que el descenso del C-LDL alcanzado con estos fármacos se asoció con una menor incidencia de eventos cardiovasculares. Dicha evidencia dio lugar a la aprobación y comercialización de los iPCSK9 en muchos países. En consecuencia, diversas sociedades científicas y organismos de referencia en salud incorporaron estos fármacos en el arsenal terapéutico de la dislipidemia, con el objetivo de reducir el riesgo cardiovascular residual. En esta revisión describiremos la eficacia y la seguridad de estos fármacos, analizaremos la evidencia disponible acerca del beneficio cardiovascular y discutiremos en qué población podría ser más efectiva su utilización.

SUMMARY Proprotein convertase subtilisin kexin type 9 (iPCSK9) inhibitors represent a new group of lipid-lowering drugs that have generated a substantial change in lipid management. In a few years, a large number of studies have evaluated the lipid efficacy and safety of these drugs. More recently, large randomized clinical trials showed that the decrease in LDL-C achieved with these drugs was associated with a lower incidence of cardiovascular events. Such evidence resulted in the approval and commercialization of iPCSK9 in many countries. Consequently, various scientific societies and health reference agencies incorporated these drugs into the therapeutic arsenal of dyslipidemia, with the aim of reducing residual cardiovascular risk. In this review, we will describe the efficacy and safety of these drugs, analyze the available evidence about cardiovascular benefit, and discuss in which population their use might be most effective.

RESUMEN

The large clinical trials on cardiovascular prevention have demonstrated that the more atherogenic cholesterol is reduced the greater the preventive benefit, and neither a threshold value below which that effect disappears nor negative effects on health have been observed. Therefore, the objectives of hypercholesterolaemia control in patients at high cardiovascular risk are becoming ever stricter. The fact that most high-risk patients do not achieve these objectives requires, among other measures, rational use of available lipid-lowering drugs, including monoclonal antibodies that inhibit the protein PCSK9 (PCSK9i). The PCSK9i that are currently licensed for clinical use, evolocumab and alirocumab, have shown high potency in lowering LDL-cholesterol, which can exceed 60%, and other favourable effects on lipid profiles, including a very marked reduction of non-HDL cholesterol and apolipoproteinB. Likewise, through large-scale clinical trials, both drugs have demonstrated a preventive effect against cardiovascular diseases, and a high degree of safety. In addition, in the case of alirocumab, a reduction in all-cause mortality has been observed. However, the high cost of the PCSK9i means that prescription is restricted to patients at highest cardiovascular risk who cannot be controlled with high-potency statins and ezetimibe. It is to be hoped that the new guidelines that are to be issued soon by various scientific societies will define in greater detail the patients and the conditions in which we can use PCSK9i, drugs which currently constitute the greatest advance in hypercholesterolaemia of recent decades.

Asunto(s)

RESUMEN

It is a patient with heterozygous familial hypercholesterolemia and a personal history of acute myocardial infarction, which is referred to our lipid unit for hypocholesterolemic treatment adjustment. Since he does not reach therapeutic goals with oral medication, he starts a treatment with fortnightly sessions of LDL-apheresis, which he keeps for 8 years. With the introduction and availability of PCSK9 inhibitors, a new treatment option is possible for this patient.

Asunto(s)

RESUMEN

Abstract: This manuscript is an addendum to the positioning around the diagnosis and treatment of dyslipidemias of ANCAM and the joint group of associated medical societies, already published. It is the first part of a wider reflection aimed on refute several of the theses and arguments of a group of clinicians and researchers who question the validity of the "cholesterol hypothesis", the usefulness and safety of statins and the most modern inhibitors of proprotein convertase of subtilisin/kexin type 9 (iPCSK9,) and the role of saturated fatty acids consumed in the usual diet in the atherosclerotic risk. This iconoclastic point of view is dangerous insofar as it undermines the scaffolding that supports the primary and secondary prevention of atherosclerosis. In this section of the manuscript, only the cholesterol hypothesis is discussed. The data of comparative zoology are reviewed, and several experimental animal models are analyzed, both supporting the link between cholesterol and the appearance and evolution of atherosclerotic lesions. The methodology and the results of the Study of the 7 Countries are defended and are exposed the numerous epidemiological, pathological, clinical and interventional evidences, which in our opinion give a solid sustenance to the cholesterol hypothesis. Based on this knowledge it is criticized the LDL cholesterol values currently considered adequate. Furthermore, the so-called residual risk is considered, as well as the conflicting evidence about the usefulness of statins in elderly patients.

Resumen: Este manuscrito es un apéndice del posicionamiento en torno al diagnóstico y tratamiento de las dislipidemias de la ANCAM y el grupo de las sociedades médicas asociadas, previamente publicado. Es la primera parte de un trabajo más amplio enfocado a refutar varias de las tesis y argumentos de un grupo de clínicos e investigadores que ponen en duda la validez de la "hipótesis del colesterol", la utilidad y seguridad de las estatinas y los más modernos inhibidores de la proproteína convertasa de la subtilisina/kexina tipo 9 (iPCSK9) y el papel de los ácidos grasos saturados consumidos en la dieta habitual en el riesgo ateroscleroso. Este punto de vista iconoclástico es peligroso porque socava el andamiaje que soporta la prevención primaria y secundaria de la aterosclerosis. En esta primera sección del manuscrito, se discute sólo la hipótesis del colesterol. Se revisan los datos de zoología comparada y se analizan varios modelos animales de experimentación, que apoyan la liga entre el colesterol y la aparición y evolución de las lesiones aterosclerosa. Se defienden la metodología y los resultados del estudio de los 7 países y se exponen las numerosas evidencias epidemiológicas, patológicas, clínicas e intervencionistas, que a nuestro juicio dan un sustento sólido a la hipótesis del colesterol. Se critican también, en base a ese conocimiento, los valores de colesterol LDL actualmente considerados adecuados, a la vez que se discute el llamado riesgo residual y las evidencias conflictivas acerca de la utilidad de las estatinas en pacientes ancianos.

RESUMEN

INTRODUCTION AND OBJECTIVES: PCSK9 inhibitors (PCSK9i) are safe and effective lipid-lowering drugs. Their main limitation is their high cost. The aim of this study was to estimate the number of patients eligible for treatment with PCSK9i according to distinct published criteria. METHODS: Data were obtained from the Information System for the Development of Research in Primary Care. Included patients were equal to or older than 18 years and had at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2 500 907). An indication for treatment with PCSK9i was assigned according to the following guidelines: National Health System, Spanish Society of Arteriosclerosis, Spanish Society of Cardiology, National Institute for Health and Care Excellence, and the European Society of Cardiology/European Atherosclerosis Society Task Force. Lipid-lowering treatment was defined as optimized if it reduced low-density lipoprotein levels by ≥ 50% and adherence was > 80%. RESULTS: Among the Spanish population aged 18 years or older, the number of possible candidates to receive PCSK9i in an optimal lipid-lowering treatment scenario ranged from 0.1% to 1.7%, depending on the guideline considered. The subgroup of patients with the highest proportion of potential candidates consisted of patients with familial hypercholesterolemia, and the subgroup with the highest absolute number consisted of patients in secondary cardiovascular prevention. CONCLUSIONS: The number of candidates to receive PCSK9i in conditions of real-world clinical practice is high and varies widely depending on the recommendations of distinct scientific societies.

Asunto(s)

RESUMEN

En los últimos años han surgido algunas investigaciones y guías de práctica clínica relacionadas con el diagnóstico y tratamiento de las dislipidemias, que aportaron nuevos conocimientos (y controversias) sobre dicha problemática. En este resumen se describen, en primer lugar, las características de las "nuevas guías" norteamericanas para el manejo del colesterol publicadas a fines de 2013 y se comparan con las recomendaciones tradicionales. En segundo lugar, se analizan los últimos estudios que evaluaron el impacto cardiovascular de otros fármacos hipolipemiantes (ezetimibe y ácido nicotínico) en pacientes en prevención secundaria tratados con estatinas. Finalmente, se mencionan las nuevas drogas hipolipemiantes desarrolladas en los últimos años, como el lomitapide, el mipomersen y los inhibidores de la PCSK9, y se comentan el mecanismo de acción, su eficacia, sus efectos colaterales y los escenarios clínicos en donde podrían utilizarse. (AU)

In recent years, some research and clinical practice guidelines related to the diagnosis and treatment of dyslipidemia, which provided new knowledge (and controversy) about this problem have emerged. In this review, the characteristics of the American "new guidelines" for cholesterol management published by the end of 2013 are described, and they are compared with the traditional recommendations. In addition, recent studies assessing the cardiovascular impact of other lipid-lowering drugs (ezetimibe and nicotinic acid) in patients in secondary prevention treated with statins are analyzed. Finally, new hypolipidemic drugs developed in recent years are mentioned (lomitapide, mipomersen and PCSK9 inhibitors), discussing the mechanism of action, efficacy, side effects and clinical settings where they could be used. (AU)

Asunto(s)