Hipertrigliceridemia severa refractaria a tratamiento médico y pancreatitis aguda recurrente: uso de plasmaféresis crónica ambulatoria en el Hospital San Pablo de Coquimbo. Reporte de un caso

Severe Hypertriglyceridemia (HTG) is associated with complications such as acute pancreatitis (AP) with high morbidity and mortality rates. We report a 42 years-old man with refractory HTG diagnosed at 19 years of age, and multiple episodes of AP, admitted with the suspicion of a new AP episode. Serum triglycerides were over 2000 mg/dl. His body mass index was 18 kg/m2, there was no evidence of xanthomas or xanthelasmas, but lipemia retinalis was found. Management included heparin and insulin, added to his usual treatment with fibrates, statins, omega-3 fatty acids, and orlistat. Due to lack of response, apheresis was started. After five sessions, triglycerides decreased to 588 mg/dl (82% reduction) and levels remained below 1000 mg/dl with daily apheresis. The patient continued with weekly sessions as outpatient with a sustained good response.

Current status of research on fibrates in treatment of primary biliary cholangitis / 临床肝胆病杂志

At present, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are approved by FDA for the treatment of primary biliary cholangitis (PBC). New drugs are urgently needed for the patients who have inadequate response to UDCA or cannot tolerate pruritus, a common side effect of OCA. In recent years, a large number of basic experiments and clinical studies have shown that fibrates have a good clinical effect in the treatment of PBC. This article reviews the advances in the mechanism and clinical application of fibrates in the treatment of PBC.

Effect of Fenofibrate Medication on Renal Function / 가정의학회지

BACKGROUND: Fibrates are widely used to treat hypertriglyceridemia, a risk factor for arteriosclerosis, but these compounds have been associated with renal dysfunction. This study aimed to investigate the effects of fibrates on renal function in relatively healthy adult subjects with no cardiovascular diseases. METHODS: This retrospective study included 558 outpatients who were prescribed 160 mg fenofibrate (fenofibrate group) or 10 mg atorvastatin (control group) between August 2007 and October 2015. The groups were randomly matched using propensity scores at a 1:1 ratio. Serum creatinine levels and estimated glomerular filtration rates before and after treatment were compared between the two groups. RESULTS: Patients in the fenofibrate group showed greater changes in serum creatinine levels than those in the control group (9.73%±9.83% versus −0.89%±7.37%, P<0.001). Furthermore, 55.1% of patients in the fenofibrate group, but only 6.1% of those in the control group, exhibited a serum creatinine level increase ≥0.1 mg/dL (P<0.001). The fenofibrate group showed significantly greater declines in the estimated glomerular filtration rate than the control group (−10.1%±9.48% versus 1.42%±9.42%, P<0.001). Moreover, 34.7% of the fenofibrate group, but only 4.1% of the control group, exhibited an estimated glomerular filtration rate decrease ≥10 mL/min·1.73 m² (P<0.001). CONCLUSION: Fenofibrate treatment resulted in increased serum creatinine levels and reduced estimated glomerular filtration rates in a primary care setting. Therefore, regular renal function monitoring should be considered essential during fibrate administration.

Combination pharmacotherapy in lipid management

Latest guidelines on lipid management recommend statins as the first-line therapy. Because limited evidence is available on cardiovascular outcomes with varying statin-nonstatin combinations, recommendation levels for these regimens have been weak. However, a recent trial has demonstrated the additive effect of the statin-ezetimibe combination. The statin-fibrate combination has shown an effect in certain subgroups and on diabetic microangiopathy. Recent trials using the statin-niacin combination have been largely negative, whereas the statin-omega-3 fatty acids combination demonstrated a positive effect only in one study. Identifying the benefits and limitations of each combination is important for the best possible management of patients.

Update on the Pharmacologic Agents for Dyslipidemia / 임상당뇨병

Although statins have demonstrated consistent and strong effects on cardiovascular prevention, non-statin drugs have failed to show additional clinical benefit. Consequently, statins are currently recommended as first-line therapy in dyslipidemia. On the contrary, non-statin drugs are indicated in limited cases in which statins are not sufficiently effective or intolerable. A recent trial on ezetimibe provides evidence supporting further prescription of this agent. Proprotein convertase subtilisin-kexin type 9 inhibitors have strong low-density lipoprotein-cholesterol-lowering effects and were just approved in Western countries. However, results of clinical outcomes are not yet available. Other non-statin lipid-modifying agents have their own roles and limitations. Thus, it is important to have correct knowledge on these agents for optimal treatment of dyslipidemic patients.

Refocusing Peroxisome Proliferator Activated Receptor-alpha: A New Insight for Therapeutic Roles in Diabetes

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-alpha, summarize data from clinical studies on the effect of PPAR-alpha agonist in diabetes, and will discuss the possible therapeutic role of PPAR-alpha activation.

Refocusing Peroxisome Proliferator Activated Receptor-alpha: A New Insight for Therapeutic Roles in Diabetes

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-alpha, summarize data from clinical studies on the effect of PPAR-alpha agonist in diabetes, and will discuss the possible therapeutic role of PPAR-alpha activation.

Rosuvastatina e ciprofibrato no tratamento da dislipidemia em pacientes com HIV / Rosuvastatin and ciprofibrate in the treatment of dyslipidemia in patients with HIV

FUNDAMENTO: A dislipidemia secundária à terapia antirretroviral potente nos pacientes com HIV está associada à significativa elevação da morbimortalidade cardiovascular por doença aterosclerótica, sendo, portanto, necessário tratamento imediato e eficaz. OBJETIVO: Demonstrar a efetividade e a segurança da rosuvastatina e do ciprofibrato no tratamento da dislipidemia associada à terapia antirretroviral potente em pacientes com HIV. MÉTODOS: Trezentos e quarenta e seis pacientes com dislipidemia foram submetidos a tratamento farmacológico: 200 pacientes com hipertrigliceridemia receberam ciprofibrato (Grupo I); 79 pacientes com hipercolesterolemia receberam rosuvastatina (Grupo II); e 67 pacientes com dislipidemia mista receberam ciprofibrato associado a rosuvastatina (Grupo III). O perfil lipídico foi avaliado antes e após o tratamento hipolipemiante, sendo feita comparação estatística pelo teste de Wilcoxon. Transaminases hepáticas e creatinofosfoquinase foram dosadas para controle de toxicidade hepática e muscular. RESULTADOS: As concentrações séricas de triglicérides e de colesterol total foram significativamente menores do que as obtidas antes do tratamento, para os três grupos experimentais (p < 0,002). Observou-se aumento significativo do HDL colesterol nos grupos experimentais I e III (p < 0,002). Nos grupos I e II, o LDL-colesterol foi significativamente menor (p < 0,001). Nenhum dos pacientes apresentou elevações de transaminases ou de creatinofosfoquinase a níveis de toxicidade significativa. CONCLUSÃO: Os resultados deste estudo demonstram que ciprofibrato, rosuvastatina ou a combinação de ambos pode ser considerada tratamento hipolipemiante efetivo, seguro e com boa tolerância nos pacientes com Aids submetidos à terapia antirretroviral potente.

BACKGROUND: Dyslipidemia secondary to highly active antiretroviral therapy in patients with HIV is associated with a significant increase in cardiovascular morbidity and mortality due to atherosclerotic disease, requiring, thus, immediate and effective treatment. OBJECTIVE: To demonstrate the effectiveness and safety of rosuvastatin and ciprofibrate in the treatment of dyslipidemia associated with highly active antiretroviral therapy in patients with HIV. METHODS: Three hundred and forty-six patients with dyslipidemia underwent pharmacological treatment as follows: 200 patients with hypertriglyceridemia received ciprofibrate (Group I); 79 patients with hypercholesterolemia received rosuvastatin (Group II); and 67 patients with mixed dyslipidemia received ciprofibrate associated with rosuvastatin (Group III). The lipid profile was assessed before and after the lipid-lowering treatment, and the Wilcoxon test was used for statistical comparison. Liver transaminases and creatine phosphokinase were measured to assess liver and muscle toxicity. RESULTS: The serum concentrations of triglycerides and total cholesterol were significantly lower than those obtained before the lipid-lowering treatment in the three experimental groups (p < 0.002). A significant increase in HDL-cholesterol was observed in Groups I and III (p < 0.002). In Groups I and II, LDL-cholesterol was significantly lower (p < 0.001). None of the patients experienced elevations in transaminases or creatine phosphokinase to significantly toxic levels. CONCLUSION: The results of this study show that ciprofibrate and rosuvastatin or a combination of both can be considered an effective, safe and well-tolerated lipid-lowering treatment for patients with AIDS on highly active antiretroviral therapy.

Como manejar os efeitos colaterais dos hipolipemiantes? / How to manage the side effects of lipid-lowering medications?

Os hipolipemiantes são medicações amplamente utilizadas no tratamento das dislipidemias, com impacto na redução da morbi-mortalidade cardiovascular. Contudo, não são fármacos isentos de efeitos colaterais. Os principais efeitos indesejáveis discutidos neste artigo são a miopatia e a hepatoxicidade. Os autores enfatizam a necessidade de cuidadosa anamnese antes de iniciar a medicação hipolipemiante, ressaltando: antecedentes clínicos, alterações metabólicas presentes, uso atual de fármacos, eventuais reações de intolerância medicamentosa, além do uso de drogas ilícitas. Faz-se necessária a estabilização dos desvios metabólicos antes da administração do hipolipemiante, por exemplo, diabetes mellitus e hipotireoidismo. Ressaltam, ainda, a importância de valorizar as queixas dos pacientes, seu diagnóstico diferencial, bem como a fármaco-vigilância em relação à interação de drogas. Deve haver monitoração clínica e laboratorial cuidadosa durante o tratamento, principalmente nos pacientes de maior risco. Com o uso cada vez mais disseminado destas medicações, além de combinações de medicações diversas, são de suma importância o reconhecimento e o correto manejo destes efeitos colaterais.

The lipid-lowering medications are widely used in the treatment of dyslipidemia and impact in reducing cardiovascular morbidity and mortality. However, these drugs are not free from side effects. The main side effects discussed in this article are myopathy and hepatotoxicity. The authors emphasize the need for careful anamnesis before starting lipid-lowering medication, considering: medical history, metabolic abnormalities, drugs currently in use, drug intolerance, and the use of illicit drugs. It is necessary to stabilize the metabolic alterations before the administration of lipid-lowering medication, for example, diabetes mellitus and hypothyroidism. It is very important to valorize patients' complaints, their differential diagnosis, as well as drug-surveillance for drug interaction. Clinical and laboratory monitoring during treatment is especially important in high risk patients. With the increasingly widespread use of these medications, and various combinations of drugs, it is extremely important to correctly recognize and manage these side effects.

Current status of research on fibrates in treatment of primary biliary cholangitis / 临床肝胆病杂志

At present, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are approved by FDA for the treatment of primary biliary cholangitis (PBC). New drugs are urgently needed for the patients who have inadequate response to UDCA or cannot tolerate pruritus, a common side effect of OCA. In recent years, a large number of basic experiments and clinical studies have shown that fibrates have a good clinical effect in the treatment of PBC. This article reviews the advances in the mechanism and clinical application of fibrates in the treatment of PBC.