Early response of hyperlipidemic subjects to simvastatin.

Seventy eight patients with hypercholesterolemia from 4 major hospitals were studied with regard to their responses to an adjustable dose of simvastatin, a HMG-CoA reductase inhibitor. They were followed for up to 6 months with 4 sample points during the drug and 2 prior to therapy. The average dose was 10.2 mg/day (S.D. 5.5). Four were controlled on 5 mg and 4 needed 30 mg per day. Thirty seven per cent had elevated serum transaminases but none to greater than twice normal. Only a third of these showed elevation of transaminases during drug therapy alone. The mean total cholesterol (TC) was 304 mg/100 ml and low density lipoprotein (LDL) was 221 mg/100 ml. These fell 70 and 60 per cent respectively and over 90 per cent of the patients reduced their TC and LDL more than the limits defined from previous long term monitoring of patients (i.e. TC fell by more than 17% and LDL by 25%). High density lipoprotein, HDL, started off at 45 mg/100 ml and rose to an average of 115 per cent. Triglyceride, TG, started off at 207 mg/100 ml and fell to about 86 per cent during simvastatin. However, in terms of the proportion of patients who responded greater than the limit previously determined (i.e. more than a 25% change for HDL and 45% for TG), only about 20 per cent significantly responded with elevation of HDL and 13 per cent dropped their TG. The response of TG was more marked at TG greater than 300 mg/100 ml.

Estatinas no tratamento da hipercolesterolemia / Statins in the hypercholesterolemia treatment

Estatinas säo drogas derivadas de microorganismos e que eficientemente interferem na síntese celular de colesterol por inibiçäo competitiva da enzima HMG-CoA-redutase. Näo obstante, as estatinas reduzem a colesterolemia por induzirem formaçäo de receptores que captam as LDL do plasma e por diminuirem a síntese de VLDL no fígado. Esta última explica o efeito parcial na queda da trigliceridemia. A eficiência das estatinas na diminuiçäo da colesterolemia é comparável à das resinas seqüestradoras de ácidos biliares, porém superios à dos fibrates e ácido nicotínico. Estatinas säo melhor toleradas do que estas últimas duas drogas, mas inferiores quanto à capacidade de diminuirem os triglicérides e de aumentarem o HDL-colesterol. Seletividade tissular varia entre as diversas estatinas, mas esta é uma questäo irrelevante tendo em vista a raridade dos efeitos colaterais. Conseqüentemente, estas drogas devem ser prescritas em razäo da potência farmacológica e do fator custo. Cinecoronarioangiografia seqüencial em pacientes com coronariopatia tratados com placebo em comparaçäo a estatinas isoladamente, indica que a doença arterial regride por métodos farmacológicos.