Boh M, Opolski G, Poredos P, Ceska R, Jezovnik M
Medical Research and Pharmacovigilance, KRKA d. d. Novo mesto, Ljubljana, Slovenia.
Int Angiol. 2011 Aug;30(4):366-74.
Generic drugs are more and more frequently used instead of originators. However, uncertainty exists with respect to therapeutic equivalence of generic product with originator one. Therefore, in this study efficacy and safety of generic atorvastatin was compared to reference product. In patients with increased low density lipoprotein cholesterol (LDL-C) levels of cholesterol and changes of total coronary risk were followed.
A randomized, double-blind, multicenter parallel study was carried out in 22 centers. The study included 148 subjects with LDL-C higher than 3 mmol/L and increased coronary risk (>9.5% in 10 years calculated according to PROCAM algorithm). After a four-week placebo run-in period, patients were randomly assigned to receive the generic or the reference atorvastatin for 12 weeks. The initial dose of the drugs was 10 mg or 20 mg depending on the baseline LDL-C value. After six weeks the dose was increased to 20 mg or 40 mg in patients who had not reached the target LDL-C value of 2.99 mmol/L.
Altogether 117 patients have been analysed in the per-protocol analysis. The GA was proven to be equally effective to the reference product as shown by the significantly equal reduction in LDL-C (GA: 37.8%, RA: 38.4%, P=NS) using the non-inferiority statistical analysis. Also other lipid parameters were significantly lowered by both drugs with the exception of HDL-C. Both drugs significantly reduced absolute coronary risk by 13% and 13.3% for the generic and the reference atorvastatin, respectively. Systolic blood pressure was also significantly reduced by approximately 10 mmHg in both study groups. Both products had similar adverse events profile. No cases of therapy withdrawal due to safety were recorded.
Both the generic and the reference atorvastatin were equally effective in correcting the lipid profile and reducing calculated absolute coronary risk in patients with hyperlipidemia and increased coronary risk. Both treatments were equally well tolerated.
仿制药越来越频繁地被用于替代原研药。然而，仿制药与原研药的治疗等效性存在不确定性。因此，在本研究中，将仿制药阿托伐他汀的疗效和安全性与参比产品进行了比较。对低密度脂蛋白胆固醇（LDL-C）水平升高的患者的胆固醇水平及总冠状动脉风险变化进行了跟踪。
在22个中心开展了一项随机、双盲、多中心平行研究。该研究纳入了148名LDL-C高于3 mmol/L且冠状动脉风险增加（根据PROCAM算法计算，10年内>9.5%）的受试者。经过为期四周的安慰剂导入期后，患者被随机分配接受仿制药或参比阿托伐他汀治疗12周。药物的初始剂量根据基线LDL-C值为10 mg或20 mg。六周后，未达到目标LDL-C值2.99 mmol/L的患者剂量增加至20 mg或40 mg。
在符合方案分析中，共分析了117例患者。使用非劣效性统计分析显示，仿制药在降低LDL-C方面与参比产品同样有效（仿制药：37.8%，参比产品：38.4%，P=无显著性差异）。除高密度脂蛋白胆固醇（HDL-C）外，两种药物均显著降低了其他血脂参数。仿制药和参比阿托伐他汀分别使绝对冠状动脉风险显著降低了13%和13.3%。两个研究组的收缩压也均显著降低了约10 mmHg。两种产品的不良事件谱相似。未记录到因安全性问题而停药的病例。
仿制药和参比阿托伐他汀在改善高脂血症且冠状动脉风险增加患者的血脂谱及降低计算得出的绝对冠状动脉风险方面同样有效。两种治疗的耐受性均良好。
