Encare clínico de las dislipemias / Clinical care of dyslipidemias / Encargo clínico de dislipidemias

Resumen: El manejo de los pacientes con dislipemias en la práctica clínica diaria implica el conocimiento de la evidencia científica relevante, la experiencia clínica, el sentido común, así como el respeto a la voluntad del paciente. La evidencia demuestra que el tratamiento hipolipemiante con estatinas reduce la morbimortalidad cardiovascular en un amplio grupo de pacientes, con un porcentaje de efectos colaterales bajo. Un punto crítico en el tratamiento es la decisión de iniciar o no dichos fármacos. Hay pacientes que tienen indicación formal de estatinas sin necesidad de hacer una evaluación del riesgo vascular. Tal es el caso de los que están en prevención secundaria, pacientes con colesterol unido a las lipoproteínas de baja densidad (C-LDL) muy alto (>190 mg/dl) y diabéticos entre 40 y 75 años. En los demás individuos la indicación de estatinas pasa en primer lugar por una evaluación formal del riesgo cardiovascular. Con este fin, las guías estadounidenses sugieren el uso de las Pooled Cohort Equations, en tanto que las guías europeas utilizan el Heartscore. Ambos scores estratifican a los pacientes en cuatro grupos según la intensidad del riesgo. El beneficio absoluto en la reducción del riesgo de eventos es tanto mayor cuanto más elevado sea el riesgo basal del paciente. Es por ello que se recomienda que tanto la intensidad del tratamiento, como el nivel de descenso objetivo de C-LDL, sean tanto mayores cuanto mayor sea el riesgo del paciente. Las recomendaciones de ambas guías no son coincidentes en algunos casos. Por lo tanto, además del riesgo cardiovascular se debe considerar el riesgo de efectos adversos potenciales y la voluntad del paciente en una discusión franca con su médico. El ezetimibe primero y los inhibidores PCSK9 después (limitados en estos momentos por costos y disponibilidad) aparecen como los grandes aliados de las estatinas, cuando no se toleran las dosis adecuadas o no se llega al C-LDL objetivo. A los efectos del abordaje del tema hemos optado por analizar cinco historias clínicas representativas de los principales escenarios clínicos que obligan al médico a tomar decisiones terapéuticas específicas.

Summary: In daily clinical practice the management of patients with dyslipidemias implies knowledge of relevant clinical scientific evidence, common sense, as respect of patient preferences. There is strong evidence that treatment of dyslipidemias mainly with statins reduces morbidity and mortality in a wide group of patients with few side effects. A critical step in management of this individuals is to make the decision of whether statin treatment is indicated or not. There are patients that have a clear indication of statin use without any further cardiovascular risk calculation. Such is the case in secondary prevention, patients with extremely high low density lipoprotein cholesterol levels (>190 mg/dl) and diabetics between 40 and 75 years-old. In all other patients, statin indication should start with a formal cardiovascular risk evaluation. American guidelines suggest using the Pooled Cohort Risk Equations and European guidelines prefer Heartscore. Both scoring systems stratify risk in four categories according to risk intensity. The absolute cardiovascular risk reduction obtained with treatment increases in parallel with the basal cardiovascular risk. This explains the recommendation that both treatment intensity and magnitude of low density lipoprotein cholesterol lowering should increase as the risk of the patient increases. Recommendations provided by American and European guidelines do not always coincide. Thus, besides basal cardiovascular risk estimation, potential adverse drug effects and patient preferences should always be considered in the context of a clinician-patient frank discussion. Ezetimibe first and PCSK9 inhibitors eventually (currently limited by costs and availability) appear as the great allies of statins, when adequate doses are not tolerated or the target is not reached. We will tackle the subject through five cases that illustrate the main clinical situations in which physicians have to adopt specific therapeutic decisions.

Resumo: O manejo de pacientes com dislipidemias na prática clínica diária envolve conhecimento de provas científicas relevantes, experiência clínica, senso comum, bem como a respeito da vontade do paciente. A evidência mostra que o tratamento hipolipemiente com estatina reduz a morbimortalidade cardiovascular em um grande grupo de pacientes com uma baixa taxa de efeitos colaterais. Um ponto crítico no tratamento desses pacientes é a decisão de iniciar ou não estas drogas. Há pacientes que têm indicação formal de estatinas sem necessidade de fazer uma avaliação de risco vascular. Tal é o caso dos pacientes que estão na prevenção secundária, pacientes com colesterol da lipoproteína de baixa densidade muito alta (>190 mg/dl) e diabéticos entre 40 e 75 anos. Em outros indivíduos a indicação de uma estatinas passa primeiro através de uma avaliação formal de risco cardiovascular. Para este fim diretrizes Americanas sugerem o uso do Pooled Cohort Equations, enquanto as directrizes europeias usam o Heartscore. Ambos scores estratificam pacientes em quatro grupos de acordo com a intensidade do risco. O benefício absoluto na redução do risco de eventos é maior quanto mais elevado seja o risco base do paciente. Por isso, recomenda-se que tanto a intensidade do tratamento e do nível de descida desejada da lipoproteína de baixa densidade, são muito maior quanto maior for o risco do paciente. As recomendações de ambas as guias em alguns casos não são coincidentes. Portanto, além do risco cardiovascular deve ser considerado o risco de efeitos adversos potenciais e a vontade do paciente em uma discussão franca entre médico e paciente. Ezetimiba primeiro e os inibidores PCSK9 depois (limitado atualmente pela disponibilidade e custo) aparecem como os grandes aliados das estatinas, quando não são toleradas doses adequadas ou não se chega ao objetivo. Para efeitos da abordagem do assunto que escolhemos para analisar cinco histórias clínicas de pacientes representativos dos principais cenários clínicos que exige do médico a tomar decisões terapêuticas específicas.

Number of Patients Eligible for PCSK9 Inhibitors Based on Real-world Data From 2.5 Million Patients.

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.

Tendencias actuales del uso de las estatinas en dislipidemias y otros efectos extralipídicos / Current trends of the use of statins for dyslipidemias and other extra lipid effects

Introducción: Los pacientes con afecciones ateroscleróticas suelen presentar concentraciones intermedias de colesterol unido a lipoproteínas de baja densidad, lo que refleja la importancia de la interacción con otros factores de riesgo. El tratamiento con estatinas mejora el pronóstico, especialmente el tratamiento intensivo, e independientemente de los valores de colesterol, lo cual hace que se deba considerar esta estrategia terapéutica como una opción y por extensión, todos los pacientes con enfermedad vascular establecida.Objetivo: Examinar las tendencias actuales en el uso terapéutico de las estatinas.Fuente de datos: se realizó una revisión bibliográfica entre 2010-2015 en las bases de datos MedLine, Hinari, Cochrane, PubMed; de revistas líderes en la publicación de temas y artículos de interés.Síntesis de los datos: Las estatinas son fármacos eficaces para disminuir la concentración de colesterol y los triglicéridos en la circulación sanguínea. Además, aumentan moderadamente el colesterol unido a lipoproteínas de alta densidad y disminuyen la incidencia de enfermedad cardiovascular aterosclerótica, por lo que se las considera medicamentos de primera elección en el tratamiento de la dislipemia aterogénica. Se ha demostrado que el tratamiento hipolipemiante con estatinas, evita la progresión de la enfermedad hacia el episodio agudo.Conclusiones: Se actualizó que el efecto de las estatinas juega un papel fundamental en los pacientes con arteriopatía. Es conveniente iniciar el tratamiento lo más precoz posible y extenderlo a sectores arteriales como el cerebrovascular y el periférico(AU)

Introduction: Patients with acute atherosclerotic conditions usually present with moderate cholesterol concentrations together with low-density lipoprotein levels, which indicates the importance of the interactions with other risk factors. Statin therapy improves prognosis after the occurrence of an acute coronary syndrome, especially in intensive care and regardless of cholesterol values, which leads to consider this therapeutic strategy as an option to be extended to all the patients with a set vascular disease.Objective: To examine the present tendencies in the statin therapy.Data sourse: A literature review was made from 2010 to 2015 in MedLine Hinari, Cochrane and PubMed databases and in leading journals in the publication of topics and articles of interest.Data synthesis: Statins are effective drugs to decrease the blood cholesterol and triglyceride levels. Besides, they increase the high density lipoprotein cholesterol and reduce the incidence of atherosclerotic cardiovascular disease, therefore, they are considered first-choice drugs for the treatment of atherogenic dyslipidemia. It has been proved that hypolipidemic treatment with statin avoids the progression of the disease into the acute stage.Conclusions: The review provides an update on the fundamental role of statins in the treatment of patients with artheropathy. It is desirable to initiate the treatment as early as possible and to extend it to other arterial areas such as cerebrovascular and peripheral ones(AU)

Tendencias actuales del uso de las estatinas en dislipidemias y otros efectos extralipídicos / Current trends of the use of statins for dyslipidemias and other extra lipid effects

Introducción: Los pacientes con afecciones ateroscleróticas suelen presentar concentraciones intermedias de colesterol unido a lipoproteínas de baja densidad, lo que refleja la importancia de la interacción con otros factores de riesgo. El tratamiento con estatinas mejora el pronóstico, especialmente el tratamiento intensivo, e independientemente de los valores de colesterol, lo cual hace que se deba considerar esta estrategia terapéutica como una opción y por extensión, todos los pacientes con enfermedad vascular establecida. Objetivo: Examinar las tendencias actuales en el uso terapéutico de las estatinas. Fuente de datos: se realizó una revisión bibliográfica entre 2010-2015 en las bases de datos MedLine, Hinari, Cochrane, PubMed; de revistas líderes en la publicación de temas y artículos de interés. Síntesis de los datos: Las estatinas son fármacos eficaces para disminuir la concentración de colesterol y los triglicéridos en la circulación sanguínea. Además, aumentan moderadamente el colesterol unido a lipoproteínas de alta densidad y disminuyen la incidencia de enfermedad cardiovascular aterosclerótica, por lo que se las considera medicamentos de primera elección en el tratamiento de la dislipemia aterogénica. Se ha demostrado que el tratamiento hipolipemiante con estatinas, evita la progresión de la enfermedad hacia el episodio agudo. Conclusiones: Se actualizó que el efecto de las estatinas juega un papel fundamental en los pacientes con arteriopatía. Es conveniente iniciar el tratamiento lo más precoz posible y extenderlo a sectores arteriales como el cerebrovascular y el periférico(AU)

Introduction: Patients with acute atherosclerotic conditions usually present with moderate cholesterol concentrations together with low-density lipoprotein levels, which indicates the importance of the interactions with other risk factors. Statin therapy improves prognosis after the occurrence of an acute coronary syndrome, especially in intensive care and regardless of cholesterol values, which leads to consider this therapeutic strategy as an option to be extended to all the patients with a set vascular disease. Objective: To examine the present tendencies in the statin therapy. Data sourse: A literature review was made from 2010 to 2015 in MedLine Hinari, Cochrane and PubMed databases and in leading journals in the publication of topics and articles of interest. Data synthesis: Statins are effective drugs to decrease the blood cholesterol and triglyceride levels. Besides, they increase the high density lipoprotein cholesterol and reduce the incidence of atherosclerotic cardiovascular disease, therefore, they are considered first-choice drugs for the treatment of atherogenic dyslipidemia. It has been proved that hypolipidemic treatment with statin avoids the progression of the disease into the acute stage. Conclusions: The review provides an update on the fundamental role of statins in the treatment of patients with artheropathy. It is desirable to initiate the treatment as early as possible and to extend it to other arterial areas such as cerebrovascular and peripheral ones(AU)

Attainment of LDL Cholesterol Treatment Goals in Children and Adolescents With Familial Hypercholesterolemia. The SAFEHEART Follow-up Registry.

INTRODUCTION AND OBJECTIVES: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. METHODS: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. RESULTS: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. CONCLUSIONS: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.

[Association between venous thrombosis and dyslipidemia]. / Asociación entre enfermedad tromboembólica venosa y dislipidemia.

BACKGROUND AND OBJECTIVE: Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. PATIENTS AND METHOD: We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. RESULTS: The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P<.0001). Of a total of 313 patients included in the study, 31% (n=97) had a recurrent thrombotic event and 23% (n=72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P=.008) and OR 2.35 (95% CI 1.24-4.45; P=.008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P=.005) and OR 2.35 (95% CI 1.24-4.45; P=.008). CONCLUSIONS: Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and post-thrombotic syndrome.