Davidson M H, Stein E A, Dujovne C A, Hunninghake D B, Weiss S R, Knopp R H, Illingworth D R, Mitchel Y B, Melino M R, Zupkis R V, Dobrinska M R, Amin R D, Tobert J A
Chicago Center for Clinical Research, Illinois, USA.
Am J Cardiol. 1997 Jan 1;79(1):38-42. doi: 10.1016/s0002-9149(96)00742-4.
The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most effective of the currently approved hypolipidemic drugs and has been shown to reduce mortality and coronary morbidity in patients with coronary artery disease. For these patients the United States National Cholesterol Education Program advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl. However, in some patients this cannot be achieved using monotherapy with simvastatin 40 mg/day, the current maximal recommended dose. To evaluate the effectiveness of extending the dosage range, 156 subjects with LDL cholesterol >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete block crossover study. Each active treatment period was 6 weeks in duration with intervening 2 week washout periods. Median reductions from baseline in LDL cholesterol were 41%, 47%, and 53% in the 40-, 80-, and 160-mg groups, respectively. The corresponding reductions in plasma TG were 21%, 23%, and 33%. High-density lipoprotein (HDL) cholesterol increased by 6% to 8% in each group. One patient (0.7%) taking 160 mg developed myopathy; 1 patient (0.7%) taking 80 mg, and 3 (2.1%) taking 160 mg had transaminase elevations > 3 times the upper limit of normal. No new or unexpected adverse effects were observed. We conclude that simvastatin at doses of 80 and 160 mg/day provides additional efficacy with a low short-term incidence of adverse effects; our results support the continued investigation of simvastatin at these doses.
羟甲基戊二酰辅酶A还原酶抑制剂辛伐他汀是目前已获批准的降血脂药物中最有效的一种，已被证明可降低冠心病患者的死亡率和冠状动脉发病率。对于这些患者，美国国家胆固醇教育计划主张将低密度脂蛋白（LDL）胆固醇降至<100mg/dl。然而，在一些患者中，使用目前最大推荐剂量的辛伐他汀40mg/天进行单一疗法无法达到这一目标。为了评估扩大剂量范围的有效性，156名LDL胆固醇>160mg/dl且甘油三酯（TG）<350mg/dl的受试者被随机分为接受40mg/天、80mg/天和160mg/天剂量辛伐他汀治疗，进行一项为期26周的双盲、3阶段、完全区组交叉研究。每个活性治疗期持续6周，中间有2周的洗脱期。40mg、80mg和160mg组的LDL胆固醇从基线的中位数降低分别为41%、47%和53%。血浆TG的相应降低分别为21%、23%和33%。每组高密度脂蛋白（HDL）胆固醇升高6%至8%。一名服用160mg的患者（0.7%）出现肌病；一名服用80mg的患者（0.7%）和三名服用160mg的患者（2.1%）转氨酶升高超过正常上限的3倍。未观察到新的或意外的不良反应。我们得出结论，80mg/天和160mg/天剂量的辛伐他汀具有额外的疗效，且短期不良反应发生率较低；我们的结果支持继续对这些剂量的辛伐他汀进行研究。
