洛伐他汀与烟酸对原发性高胆固醇血症的比较效果。一项前瞻性试验。

Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial.

作者信息

Illingworth D R, Stein E A, Mitchel Y B, Dujovne C A, Frost P H, Knopp R H, Tun P, Zupkis R V, Greguski R A

机构信息

Department of Medicine, Oregon Health Sciences University, Portland.

出版信息

Arch Intern Med. 1994 Jul 25;154(14):1586-95.

PMID:8031206

Abstract

BACKGROUND

Niacin and lovastatin are both effective drugs for the treatment of hypercholesterolemia and are among the drugs of first choice recommended by the adult treatment panel. To date, however, no studies have directly compared the lipoprotein-modifying effects and safety of lovastatin and niacin across their usual dosage range in patients with primary hypercholesterolemia.

METHODS

The efficacy and safety of lovastatin and niacin were compared in a controlled, randomized, open-label study of 26 weeks' duration that was conducted at five lipid clinics. One hundred thirty-six patients with primary hypercholesterolemia participated in the study. Entry criteria were a low-density lipoprotein (LDL) cholesterol level greater than 4.37 mmol/L (160 mg/dL) with coronary heart disease and/or more than two coronary heart disease risk factors or an LDL cholesterol level greater than 5.19 mmol/L (190 mg/dL) in patients without coronary heart disease or less than two coronary heart disease risk factors. The study consisted of a 4-week diet run-in period after which eligible patients were randomly assigned to receive treatment with either lovastatin (20 mg/d) or niacin (1.5 g/d) for 10 weeks. On the basis of the LDL cholesterol response and patient tolerance, the doses were sequentially increased to 40 and 80 mg/d of lovastatin or 3 and 4.5 g/d of niacin after 10 and 18 weeks of treatment, respectively.

RESULTS

In the two patient groups, 66% of patients treated with lovastatin and 54% of patients treated with niacin underwent full dosage titration. At all time points, lovastatin was significantly (P < .01) more effective than niacin in reducing LDL cholesterol levels (26% vs 5% at week 10, 28% vs 16% at week 18, and 32% vs 23% at week 26), whereas niacin was more effective (P < .01) in increasing high-density lipoprotein cholesterol levels (6% vs 20% at week 10, 8% vs 29% at week 18, and 7% vs 33% at week 26). Niacin reduced Lp(a) lipoprotein levels by 35% at week 26, whereas lovastatin had no effect. Cutaneous flushing was the most common side effect during treatment with niacin.

CONCLUSIONS

Lovastatin and niacin both exerted favorable dose-dependent changes on the concentrations of plasma lipids and lipoproteins. Lovastatin was more effective in reducing LDL cholesterol concentrations, whereas niacin was more effective in increasing high-density lipoprotein cholesterol concentrations and reducing the Lp(a) lipoprotein level. Lovastatin was better tolerated than niacin, in large part because of the common cutaneous side effects of niacin.

摘要

背景

烟酸和洛伐他汀都是治疗高胆固醇血症的有效药物，也是成人治疗小组推荐的首选药物。然而，迄今为止，尚无研究在原发性高胆固醇血症患者的常用剂量范围内直接比较洛伐他汀和烟酸的脂蛋白调节作用及安全性。

方法

在五家血脂诊所进行了一项为期26周的对照、随机、开放标签研究，比较洛伐他汀和烟酸的疗效及安全性。136例原发性高胆固醇血症患者参与了该研究。入选标准为：患有冠心病且低密度脂蛋白（LDL）胆固醇水平大于4.37 mmol/L（160 mg/dL）和/或有两个以上冠心病危险因素，或无冠心病且冠心病危险因素少于两个的患者，其LDL胆固醇水平大于5.19 mmol/L（190 mg/dL）。研究包括为期4周的饮食导入期，之后符合条件的患者被随机分配接受洛伐他汀（20 mg/d）或烟酸（1.5 g/d）治疗10周。根据LDL胆固醇反应和患者耐受性，分别在治疗10周和18周后，将洛伐他汀剂量依次增至40和80 mg/d，或将烟酸剂量增至3和4.5 g/d。

结果

在两个患者组中，接受洛伐他汀治疗的患者中有66%以及接受烟酸治疗的患者中有54%进行了全剂量滴定。在所有时间点，洛伐他汀在降低LDL胆固醇水平方面均显著（P < 0.01）优于烟酸（第10周时分别为26%对5%，第18周时为28%对16%，第26周时为32%对23%），而烟酸在升高高密度脂蛋白胆固醇水平方面更有效（P < 0.01）（第10周时为6%对20%，第18周时为8%对29%，第26周时为7%对33%）。烟酸在第26周时使Lp(a)脂蛋白水平降低了35%，而洛伐他汀无此作用。皮肤潮红是烟酸治疗期间最常见的副作用。