Peters T K, Muratti E N, Mehra M
Clinical Research and Development, Sandoz Pharma Ltd., Basel, Switzerland.
Am J Med. 1994 Jun 6;96(6A):79S-83S. doi: 10.1016/0002-9343(94)90236-4.
Patients with primary hypercholesterolemia and established coronary artery disease (CAD) with additional associated risk factors for atherosclerosis are considered for lipid-lowering drug therapy at lower levels of total and/or low-density lipoprotein cholesterol (LDL-C) than are patients with isolated hypercholesterolemia. As regards prevention of cardiovascular morbid events, high-risk patients are expected to receive the most benefit from lipid-lowering treatment. Thus, it is of interest to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a new, wholly synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in patients at high risk. A retrospective analysis was based on data from controlled clinical trials in which 1,815 patients were treated with fluvastatin at a daily dose of > or = 20 mg and 783 patients received placebo. Of the fluvastatin-treated patients, 328 (18.1%) had CAD compared with 136 (17.4%) patients taking placebo. Within these groups, 186 fluvastatin patients and 75 placebo patients had at least one of the following additional risk factors: hypertension, obesity, and/or fasting blood glucose levels above the upper limit of normal (ULN). Patients at high risk, as defined above, were compared with patients without CAD or any risk factors (fluvastatin, n = 837; placebo, n = 375). The effect of 40 mg of fluvastatin on LDL and high-density lipoprotein cholesterol (HDL-C), and triglycerides tended to be enhanced in patients at high risk (HR) compared with those at low risk (LR). Changes from baseline in HR patients were: LDL-C, -26.6%; HDL-C, 6.4%; triglycerides, -13%. Changes in LR patients were: LDL-C, -24.8%; HDL-C, 4.4%; triglycerides, -6%. All of these changes were highly significant (0.001 < p < 0.01). No patient in the HR group experienced a confirmed (measured on two consecutive occasions) increase > 3 x ULN in aspartate (ASAT) or alanine (ALAT) aminotransferases, nor any notable increases in creatine kinase > 10 x ULN. The tolerability of fluvastatin, as assessed by analysis of adverse events, was not consistently influenced by concomitant high risk. This exploratory analysis of the efficacy and safety profile of fluvastatin in patients at high risk for atherosclerosis suggests that such treatment is efficacious, safe, and well tolerated. The observed tendency toward an improved efficacy in the high-risk group will need further confirmation using data from prospective studies in such patients.
与单纯高胆固醇血症患者相比，患有原发性高胆固醇血症且已确诊冠状动脉疾病（CAD）并伴有其他动脉粥样硬化相关危险因素的患者，在总胆固醇和/或低密度脂蛋白胆固醇（LDL-C）水平较低时即会考虑给予降脂药物治疗。就预防心血管疾病不良事件而言，高危患者有望从降脂治疗中获得最大益处。因此，评估新型降脂药物氟伐他汀（一种全新的全合成3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂）在高危患者中的疗效、安全性和耐受性具有重要意义。一项回顾性分析基于对照临床试验的数据，其中1815例患者接受每日剂量≥20 mg的氟伐他汀治疗，783例患者接受安慰剂治疗。在接受氟伐他汀治疗的患者中，328例（18.1%）患有CAD，而接受安慰剂治疗的患者为136例（17.4%）。在这些组中，186例氟伐他汀治疗患者和75例安慰剂治疗患者具有以下至少一种其他危险因素：高血压、肥胖和/或空腹血糖水平高于正常上限（ULN）。将上述定义的高危患者与无CAD或任何危险因素的患者进行比较（氟伐他汀组，n = 837；安慰剂组，n = 375）。与低危（LR）患者相比，40 mg氟伐他汀对高危（HR）患者的LDL和高密度脂蛋白胆固醇（HDL-C）以及甘油三酯的影响趋于增强。HR组患者相对于基线的变化为：LDL-C，-26.6%；HDL-C，6.4%；甘油三酯，-13%。LR组患者的变化为：LDL-C，-24.8%；HDL-C，4.4%；甘油三酯，-6%。所有这些变化均具有高度显著性（0.001 < p < 0.01）。HR组中没有患者的天冬氨酸（ASAT）或丙氨酸（ALAT）转氨酶出现经确认（连续两次测量）升高超过3×ULN的情况，肌酸激酶也没有出现超过10×ULN的显著升高。通过不良事件分析评估的氟伐他汀耐受性并未受到伴随的高危状态的持续影响。这项对氟伐他汀在动脉粥样硬化高危患者中的疗效和安全性的探索性分析表明，这种治疗方法有效、安全且耐受性良好。高危组中观察到的疗效改善趋势需要使用此类患者前瞻性研究的数据进行进一步证实。
