Effectiveness of lipid-lowering therapy among a sample of patients in Colombia / Eficacia del tratamiento hipolipemiante en una muestra de pacientes de Colombia

OBJECTIVE: To determine the effectiveness of lipid-lowering therapy in a sample of patients affiliated with the Sistema General de Seguridad Social en Salud (the Colombian health system). METHODS: A cross-sectional study was conducted from 1 January 2010-30 June 2011. From a total of 8 316 patients in 10 cities, a random sample of 600 was stratified according to dyslipidemia. Information on sociodemographic and anthropometric characteristics, risk factors, and pharmacological and laboratory variables were obtained from medical records. RESULTS: Subjects were predominantly female (56.2%), with a mean age of 65.1 ± 11.5 years; 93.2% had hypertension; 29.0%, diabetes mellitus; and 10.2%, a history of myocardial infarction. The patients were being treated with lovastatin (84.1%) or gemfibrozil (12.3%)-both at doses below what is recommended-or atorvastatin (1.8%). In patients with high cardiovascular risk, 38.6% achieved goals for low-density lipoprotein cholesterol (LDL-C) levels (<100 mg/dL). Among those at moderate risk, 49.4% reached the target level (< 130 mg/dL). On average, there was a 4.9% reduction in LDL-C. Sex, age, history of cardiovascular disease and/or diabetes mellitus, use of hydrochlorothiazide, and poor therapy adherence were statistically associated with a lack of dyslipidemia control. CONCLUSIONS: Because a lack LDL-C control occurred in patients with two or more of the following variables: male, more than 55 years of age, diabetes and/or a history of cardiovascular disease, received lower doses of lovastatin, or non-adherent to treatment, it is recommended that medication be increased based on clearly-defined therapeutic goals and that comorbidities be assessed and effectively treated.

OBJETIVO: Determinar la eficacia del tratamiento hipolipemiante en una muestra de pacientes afiliados al Sistema General de Seguridad Social en Salud de Colombia. MÉTODOS: Se llevó a cabo un estudio transversal desde el 1 de enero del 2010 al 30 de junio del 2011. De un total de 8 316 pacientes de 10 ciudades seleccionadas, se estratificó una muestra aleatoria de 600 pacientes en función de la dislipidemia. A partir de los expedientes médicos, se obtuvo información sobre las características sociodemográficas y antropométricas, los factores de riesgo y las variables farmacológicas y de laboratorio. RESULTADOS: En la muestra predominaban las mujeres (56,2%) y la media de la edad era de 65,1 ± 11,5 años; 93,2% de los pacientes eran hipertensos; 29,0% eran diabéticos; y 10,2% tenían antecedentes de infarto de miocardio. Los pacientes recibían tratamiento con lovastatina (84,1%) o gemfibrozilo (12,3%) -ambos a dosis inferiores a las recomendadas- o atorvastatina (1,8%). El 38,6% de los pacientes con alto riesgo de enfermedad cardiovascular alcanzaron los objetivos de reducción de los niveles de colesterol unido a lipoproteínas de baja densidad (C-LDL) (< 100 mg/dL). El 49,4% de los pacientes que presentaban un riesgo moderado también alcanzaron los niveles fijados como objetivo (< 130 mg/dL). En promedio, hubo una reducción de 4,9% del C-LDL. El sexo, la edad, los antecedentes personales de enfermedad cardiovascular y diabetes, la administración de hidroclorotiazida y la deficiente adherencia al tratamiento se asociaron estadísticamente con una falta de control de la dislipidemia. CONCLUSIONES: Dado que se produjo un control deficitario del C-LDL en pacientes con dos o más de las siguientes variables: varones, mayores de 55 años, diabéticos o con antecedentes de enfermedad cardiovascular, que recibían dosis bajas de lovastatina, o mostraban falta de adherencia al tratamiento, se recomienda que se aumente la medicación con base en objetivos terapéuticos claramente definidos y que se evalúen y se traten eficazmente las comorbilidades.

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats / Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES: Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

Brote psicótico agudo y rabdomiólisis tras el uso de lovastatina / Psychotic acute episode and rhabdomyolysis after lovastatin ingestion

Introducción: Las estatinas son los medicamentos más recetados en el mundo, por el beneficio y la seguridad que ofrecen. Sin embargo, pueden causar reacciones adversas a escala neurológica, gastrointestinal, renal y muscular. Objetivo: Es describir el curso clínico de una paciente con reacción adversa medicamentosa a la lovastatina. Métodos: Reporte de caso y revisión de la literatura. Resultados: Mujer de 52 años con psicosis súbita y rabdo-miólisis secundaria al consumo de lovastatina, clínica que remite con la suspensión del fármaco. La relación causal se establece a través de la escala de Naranjo, con puntuación de 6 (probable reacción adversa medicamentosa). Conclusión: La manifestación simultánea de psicosis y rabdomiólisis representa un caso clínico atípico y único consecuente a la ingesta de lovastatina…

Introduction: Statins are the most prescribed drugs worldwide given the benefit and security they offer. However, they can cause severe neurological, gastrointestinal, renal and mus-cular side effects. Objective: To describe the clinical course of a female patient with adverse drug reaction to Lovastatin. Methods: Case report and literature review. Results: 52-year old woman with sudden psychosis and rhabdomyolysis secondary to Lovastatin and ending after the drug suspension. The causal relationship was corroborated with a score of 6 (probable ADR) on Naranjo’s Scale. Conclusions: The simultaneous manifestation of psychosis and rhabdomiolysis represents an atypical and unique case following Lovastatin ingestion…

Las estatinas afectan la viabilidad de líneas celulares de leucemia y linfoma humanas in vitro / Statins affect the viability of leukemia cell lines in vitro and human lymphoma

Se ha propuesto que las estatinas inducen apoptosis sobre células tumorales. Para probar dicha hipótesis, se analizó el efecto de las estatinas atorvastatina, fluvastatina, lovastatina, mevastatina, pravastatina y simvastatina en el rango de concentraciones de 1 pM hasta 100 µM, sobre la viabilidad de las líneas celulares humanas Jurkat E6.1, Jurkat D1.1 (Linfoma T) , Daudi (Linfoma B), U937 (leucemia monocítica) y HL-60 (leucemia promielomonocítica) in vitro en cultivos de 48 horas, analizados por la técnica de hidrolización del compuesto bromuro de 3-(4,5-dimetiltiazol-2-il)-2,5-difenilltetrazolio (MTT). Lovastatina y mevastatina son los más potentes inductores de muerte celular independientemente del tipo celular (Ic 50 entre 12 y 50 µM). Para las otras estatinas se observan diferencias en el Ic50 según la línea celular atorvastatina (38,1 y 48,6 µM Jurkats, 55,3 µM Daudi y 100 µM para las otras líneas), pravastatina (25 µM HL-60, 55,6 y 60,7 µM Jurkats y > 100 µM Daudi y U937), simvastatina (25,1 µM Jurkat D1.1, 50,2 µM Jurkat E6.1, 45,2 µM Daudi y 51,3 µM HL-60, y > 100 µM U937) y para fluvastatina en todos los casos > 100 µM. La disminución de la viabilidad celular se revierte completamente cuando las células son incubadas con 10 µM mevalonato. Se concluye que la lovastatina y mevastatina son las más potentes inductoras de muerte seguida por atorvastatina, pravastatina y simvastatina cuyo efecto depende del tipo de línea celular y la fluvastatina no tiene efectos importantes en la viabilidad de las líneas celulares estudiadas

Statins have been proposed to induce apoptosis of tumor cells. In order to test this hypothesis, the effect of atorvastatin, fluvastatin, lovastatin, mevastatin, pravastatin, simvastatin on cell viability was assessed by in vitro culture for 48 hr, at concentrations ranging from 1 pM to 100 µM on human cell lines Jurkat E6.1, Jurkat D1.1 (T cell lymphoma), Daudi (B cell lymphoma), U937 (monocitic leukemia) and HL-60 (pro mielomonocitic leukemia) and analyzed the oxidation of (3-(4.5-Dimethylthiazol-2-yl)-2.5- diphenyltetrazolium bromide (MTT). Lovastatin and mevastatin are the most potent inductors of cell death independently of the cell type (Ic 50 between 12 and 50 µM). Differences in the Ic50 are observed depending on the cell line: atorvastatina (38.1 and 48.6 µM Jurkats, 55.3 µM Daudi y 100 µM for the others lines), pravastatin (25 µM HL-60, 55.6 y 60.7 µM Jurkats and > 100 µM Daudi and U937), simvastatin (25.1 µM Jurkat D1.1, 50.2 µM Jurkat E6.1, 45.2 µM Daudi and 51,3 µM HL-60, and > 100 µM U937) and for fluvastatin > 100 µM in all cases. The decrease in cell viability is reverted completely when the cells were incubated with 10 µM mevalonate. It is concluded that lovastatin and mevastatin are the most potent inductors of cell death followed by atorvastatin, pravastatin and simvastatin whose effect depends upon the cell type and fluvastatin does not have any important effects on cell viability on the cell lines studied

Proteção funcional do rim com lovastatina após isquemia e reperfusão renal

Acute kidney ischemia is a frequent clinical problem in vascular and urologic surgery, as in cadaver donor transplantation. In the search for an improvement in renal function, in this study we assessed the effect of lovastatin on kidney ischemia-reperfusion. Adult Wistar rats were submitted to 60 minutes of unilateral kidney ischemia followed by contralateral nephrectomy, with 7 days of follow-up. The experimental group (n=14) received 15 mg/Kg/day of lovastatin and the control group (n=17) had no protection against kidney ischemia. Serum urea and cretinine, death rate and mitochondrial function were analysed into each group. Death rate was 29.4% in group A and 0.7% in group B. Serum levels of urea and creatinine raised in both group, but in group B these values were statistically lower. In 83.4% of the group A animals mitochondrial function showed no ATP production, and in group B this condition was seen in only 38.4%. These results suggest that lovastatin has a protective effect on renal function when administered before kidney ischemia. However, at this moment it is impossible to confirm that this action is due to a protective effect on mitochondrial function.

Introdução - a isquemia renal é causa de graves lesões nesse órgão, estando presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. Assim, a procura de substâncias protetoras da função renal tem amplo interesse clínico. Neste estudo o objetivo foi o de analisar o efeito da lovastatina na isquemia renal normotérmica seguida da reperfusão.

A lovastatina no tratamento da hipercolesterolemia em portadores de diabete näo dependente de insulina / Lovastatin for the Treatment of Hypercholesterolemia in Non-insulin Dependent Diabetic Patients

Objetivo - Avaliar os efeitos da lovastatina como agente capaz de corrigir as anormalidade do perfil lipídico do plasma em pacientes diabéticos näo dependentes de insulina (NIDDM) e portadores de hipercolesterolemia. Métodos - Foram estudados 20 pacientes NIDDM nos quais se diagnosticou hipercolesterolemia, definida como a ocorrência de níveis de LDL-colesterol superiores a 160mg/dl, em pacientes do sexo feminino, e acima de 130mg/dl em pacientes do sexo masculino, ou em mulheres portadoras de qualquer outro fator de risco para doença coronariana. Dos 20 pacientes incluídos, 18 eram hipertensos que foram admintidos no estudo após terem substituído a terapêutica com ß-bloqueadores ou diurêticos por inibidores da enzima conversora ou bloqueadores dos canais de cálcio. O tratamento consistiu na administraçäo de lovastatina por um período de 24 semanas. A dose diária inicial de 20mg era elevada para 40mg, após 6 semanas de uso da droga, caso os níveis de LDL-colesterol se mantivessem acima de 130mg/dl. Resultados - A lovastatina na dose diária de 20mg (9 pacientes) ou 40mg (11 pacientes), reduziu os níveis séricos de LDL-colesterol e do colesterol total em 30// e 21// respectivamente, enquanto os níveis de HDL-colesterol e triglicérides permaneceram inalterados. A medicaçäo foi bem tolerada e nenhum paciente apresentou alteraçöes nos níveis séricos das transaminases ou bilirrubinas. Em 9 dos pacientes estudados houve elevaçäo dos níveis séricos da fosfatase alcalina, sendo que a média do grupo todo se elevou de 109 ñ 59 para 188 ñ 60mµ (p < 0,05), sendo esta a única alteraçäo laboratorial observada, näo associada a qualquer manifestaçäo clínica. Conclusäo - Em NIDDM a lovastatina se mostrou eficiente para promover reduçöes nos níveis séricos do colesterol total e do LDL-colesterol. Embora se desconheça o real significado da elevaçäo nos níveis séricos da fosfatase alcalina, recomendamos, nessa condiçäo, a suspensäo da terapia com essa droga

Purpose- To evaluate the effects of lovastatin as an hypocholesterolemic agent in non-insulin dependent diabetic (NIDDM) patients with high cholesterol plasma levels. Methods - Twenty NIDDM patients were included in this study. Hypercholesterolemia was defined as LDL cholesterol plasma levels above 160mg/dl in female patients and above 130mg/dl in male patients or in women presenting any other risk factor for cardiovascular disease. From the 20 patients included, 18 had also high levels of arterial blood pressure. They were evaluated for admission in the study after they have substituted the antihypertensive medication for at least 6 weeks, from bblockers or diuretics to angiotensin converting enzyme inhibitors or calcium channel blockers. Lovastatin was administered in a initial daily dose of 20mg to all patients for 6 weeks. After this period this dose was increased to 40mg in 11 patients with LDL-cholesterol levels above 130mg/dl. All patients were treated for a total period of 24 weeks. Results - Lovastatin therapy for 24 weeks reduced LDL-cholesterol and total cholesterol plasma levels in 30% and 21°/, respectively, while no changes in HDL cholesterol or triglycerides plasma levels wereobserved. The medication was well tolerated and no changes in bilirrubins or transaminases plasma levels were detected. In 9 patients the serum levels of alkaline phosphatase showed an elevation and the mean level of all group increased from 109±59 to 188±60mm/ml (p< 0.05). This was an isolated abnormality without any other clinical manifestation. Conclusion - Lovastatin in NIDDM showed to be an efficient agent to reduce high levels of LDL-cholesterol and total cholesterol. However, the importance of the abnormality observed in serum alkaline phosphatase levels deserves further investigation. In this condition we recommend discontinuation of lovastatin therapy

Efeito da lovastina e do probucol sobre as fraçöes lipídicas de indivíduos com hipercolesterolemia: estudo multicêntrico brasileiro / Effects of lovastatin and probucol on lipoprotein fractions in patients with primary hypercholesterolemia: a Brazilian multicenter study

Objetivo Comparar efeitos da administração de lovastatina e de probucol nas frações lipoprotéicas em indivíduos com hipercolesterotemia primária. Métodos Sessenta e nove pacientes que mantidos com dieta adequada e por quatro semanas sob uso de placebo (PLAC) permaneceram com colesterolemia total (CT) acima de 250 mg/dl. Lovastatina foi administrada a 31 pacientes na dose de 20 mg/dia, sendo aumentada para 40 mg/dia se ao final da 5a semana de tratamento os valores da CT se mantivessem acima de 200 mg/dl. Probucol prescrito a 38 pacientes na dose de 500 mg, duas vezes ao dia. O estudo foi realizado por 12 semanas. Dosagens de colesterolemia total (CT), trigliceridemia (TG), HDL-C, colesterol não HDL, LDL-C, VLDL-C e relações CT/ HDL-C e LDL-C/HDL-C e exames laboratoriais de controle foram feitos em PLAC, na 5a e 12a semanas de tratamento. Foram realizados também exames clínico e oftalmológico e anotados os eventuais efeitos adversos. Resultados A lovastatina provocou reduções de CT, LDL-C, colesterol não HDL e das relações CT/HDL-C e LDL-C/HDL-C respectivamente de 27,9,34,1,3,2,30,9 e 36,5%, significativamente mais acentuadas que as induzidas por probucol, (respectivamente 21,7, 23,8, 24,5, 11,3 e 13,4%); a lovastatina foi responsável pela elevação dos valores de HDL-C em 6,8%, enquanto que probucol provocou redução de 6,9%; 5,8% e 51,6% dos sob uso de lovastatina tiveram respectivamente redução das relações CT/HDL-C e LDL-C/HDL-C. Sob efeito de probucol, essas reduções ocorreram, respectivamente, em 15,7% e 13,1%; a lovastatina foi responsável por 77,4% e 77,3% das respostas ótimas e boas para CT e LDL-C. As respostas regulares e precárias foram mais freqüentemente observadas com o uso do probucol (39,4% cada); a freqüência dos efeitos adversos foi baixa e a tolerância satisfatória para as duas drogas. Conclusão A lovastatina foi mais eficaz para a redução dos níveis sangüíneos das frações aterogênicas e para a elevação da fração protetora, com redução mais acentuada dos índices de risco. Com seu uso, permitindo atingir mais facilmente os níveis ideais de CT e LDL-C, deverá ocorrer maior benefício sobre a morbidade e mortalidade por doença arterial coronariana

Purpose The changes in lipoproteins induced by lovastatin (L) and probucol (P) were compared in patients with primary hypercholesterolemia. Methods—After a six-week period of screening, during which patients were maintained on lipid-lowering diet, they were administered placebo for four weeks. Those patients. whose total cholesterol (TC) remained above 250 mg/dl were eligible for active treatment. Thirty-one patients were administered L and P for 12 weeks. The initial dosage of L was 20 mg daily and it was titrated up to 40 mg daily at the end of the fifth week of treatment, whenever total cholesterol levels remained above 200 mg/dl; P was administered at a dosage of 500 mg b.i.d. through 12 weeks. Lipid analyses (TC, triglycerides-Tg, high-density cholesterol (HDL-C) non HDL cholesterol, low-density cholesterol (LDL-C) very lowdensity cholesterol (VLDL-C) and the ratios CT/HDL-C and laboratory safety measurements were performed during placebo period and at the end of the 5th and 12th weeks of active treatment. Clinical and ophthalmological evaluations were performed and eventual adverse reactions were recorded on different occasions. Results—1) L induced decrease of TC, LDL-C/HDL-C of 27.9,34.1,32.2,30.9 and 36.5% respectively. These reductions were significantly more pronounced than those induced by P (21.7, 23.8, 24.5, 11.3 and 13.4% respectively); 2) L induced an increase of HDL-C of 6.8%, while P induced a reduction of HDL-C of 6.9%; 3) 54.8% and 51.6 % of the patients treated with L showed reductions of the ratios TC/HDL-C and LDL-C/HDL-C respectively The patients who were administered P showed decrease in those indices of 15.7% and 13.1% respectively; 4) L was associated with 77.4% and 77.3% of excellent and good responses for TC and LDL-C. Regular and poor responses were more frequently observed during the treatment with P (39.4% each); 5) the incidence of adverse reactions was low and tolerability was considered good for both drugs. Conclusion Lovastatin was more effective in the reduction of atherogenic lipoprotein fraction and in the increase of the protective one, with more pronounced reduction of the risk indices. They suggest that with the administration of L, that leads to an approapriate normalization of TC and LDL-C levels, greater benefits on morbidity and mortality of coronary disease can be achieved

Comparação entre lovastatina e o gemfibrozil no tratamento de hiperlipidemias primárias / Comparison between lovastatin and gemfibrozil in treatment of primary hyperlipidemias

Purpose - To compare the effects of lovastatin and gemfibrozil in patients with primary hyperlipidemias. Patients and Methods - Forty patients with cholesterolemia over 200 mgldl and triglyceridemia not higher than 350 mp/dl, excluded secondary causes, were selected. Twenty patients received lovastatin and 20 gemfibrozil. In order to establish the lipid profile, blood samples were taken after 2 months without medication, after 4 weeks of diet and placebo and after 6 and 12 weeks active treatment. Biochemic profile was determined before and after the treatment with active drug. Results - Thirty nine patients completed the study. Total and LDL-cholesterol were significantly reduced (p < 0.05) by both drugs but lovastatin had greater effect. Only gemfibrozil reduced triglycerides significantly. Neither drug had significant effects on HDL-cholesterol. The tolerance was satisfactory; only one patient (using gemfibrozil) needed to stop the treatment due to gastrointestinal side effects. The biochemic profïle did not present any significant alteration. Conclusion - Both drugs produced useful effects on the lipid profile. Lovastatin produced greater reductions of total and LDL-cholesterol, while gemfibrozil was more active reducing triglycerides. Neither drug changed significantly the HDL-cholesterol