使用HMG CoA还原酶抑制剂治疗高胆固醇血症：辛伐他汀与普伐他汀的直接比较。

Lintott C J, Scott R S, Sutherland W H, Bremer J

Lipid and Diabetes Research Group, Christchurch Hospital, New Zealand.

Aust N Z J Med. 1993 Aug;23(4):381-6. doi: 10.1111/j.1445-5994.1993.tb01439.x.

BACKGROUND

Simvastatin and pravastatin are both competitive inhibitors of the rate limiting enzyme for cholesterol biosynthesis (HMG CoA) reductase, but data from individual clinical trials suggest significant differences in potency for cholesterol reduction between the two drugs.

AIM

To assess any differences in efficacy and safety between simvastatin and pravastatin in a direct, comparative study.

METHODS

A double-blind, double-dummy, randomised study design was used, involving 48 patients with primary hypercholesterolaemia. Following a 6 week placebo baseline period, patients were randomly allocated to treatment with either simvastatin or pravastatin, commencing at a dose of 10 mg daily. The dose levels were titrated up to the recommended maximum effective dose of 40 mg daily at 6 weekly intervals if LDL cholesterol levels remained > or = 3.4 mmol/L. After 18 weeks of therapy, all patients were transferred to simvastatin therapy for a further 6 weeks, continuing at their week 18 dose level. Patients complied with a standard lipid lowering diet (containing < 30% of energy as total fat) throughout the study period.

RESULTS

Over the 18 week direct comparison of the two drugs, there was a significant difference (p < 0.001) in response between simvastatin and pravastatin for reduction in levels of total cholesterol (32% vs 21% respectively), LDL cholesterol (38% vs 27%) and apolipoprotein B levels (34% vs 23%). No significant difference in drug effect was seen for the small reduction in levels of apolipoprotein AI (5% vs 6% respectively), nor for the increased levels of apolipoprotein AII (14% vs 11%) and HDL cholesterol (11% vs 7%). Lp(a) levels remained unchanged. When pravastatin was replaced with simvastatin for the final 6 weeks of the study in the 23 patients initially randomised to pravastatin, there were further reductions (p < 0.01) in total and LDL cholesterol, and apolipoprotein B. These results establish the advantage of simvastatin over pravastatin in terms of efficacy, for the treatment of primary hypercholesterolaemia.

背景

辛伐他汀和普伐他汀均为胆固醇生物合成限速酶（HMG CoA）还原酶的竞争性抑制剂，但来自个别临床试验的数据表明，两种药物在降低胆固醇效力方面存在显著差异。

目的

在一项直接对比研究中评估辛伐他汀和普伐他汀在疗效和安全性上的任何差异。

方法

采用双盲、双模拟、随机研究设计，纳入48例原发性高胆固醇血症患者。经过6周的安慰剂基线期后，患者被随机分配接受辛伐他汀或普伐他汀治疗，起始剂量为每日10 mg。如果低密度脂蛋白胆固醇水平仍≥3.4 mmol/L，则每隔6周将剂量滴定至推荐的最大有效剂量每日40 mg。治疗18周后，所有患者转用辛伐他汀治疗再持续6周，维持第18周的剂量水平。在整个研究期间，患者遵循标准的降脂饮食（总脂肪能量占比<30%）。

结果

在对两种药物进行的18周直接比较中，辛伐他汀和普伐他汀在降低总胆固醇水平（分别为32%和21%）、低密度脂蛋白胆固醇（38%和27%）和载脂蛋白B水平（34%和23%）方面的反应存在显著差异（p<0.001）。对于载脂蛋白AI水平的小幅降低（分别为5%和6%）、载脂蛋白AII水平的升高（14%和11%）以及高密度脂蛋白胆固醇水平的升高（11%和7%），未观察到药物效果的显著差异。脂蛋白（a）水平保持不变。在最初随机分配接受普伐他汀治疗的23例患者中，在研究的最后6周将普伐他汀替换为辛伐他汀后，总胆固醇、低密度脂蛋白胆固醇和载脂蛋白B进一步降低（p<0.01）。这些结果确立了辛伐他汀在治疗原发性高胆固醇血症方面相对于普伐他汀的疗效优势。