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

RESUMO

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

ABSTRACT

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