Athyros Vasilios G, Papageorgiou Athanasios A, Mercouris Bodosakis R, Athyrou Valasia V, Symeonidis Athanasios N, Basayannis Elias O, Demitriadis Dimokritos S, Kontopoulos Athanasios G
Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.
Curr Med Res Opin. 2002;18(4):220-8. doi: 10.1185/030079902125000787.
Atorvastatin is very effective in reducing plasma low-density lipoprotein cholesterol (LDL-C) levels. However, there is no long-term survival study that evaluated this statin.
PATIENTS-METHODS: To assess the effect of atorvastatin on morbidity and mortality (total and coronary) of patients with established coronary heart disease (CHD), 1600 consecutive patients were randomised either to atorvastatin or to 'usual' medical care. The dose of atorvastatin was titrated from 10 to 80 mg/day, in order to reach the National Cholesterol Education Program (NCEP) goal of LDL-C <100 mg/dl (2.6 mmol/l). All patients were followed up for a mean period of 3 years.
Primary endpoints of the study were defined as death, non-fatal myocardial infarction, unstable angina, congestive heart failure, revascularisation (coronary morbidity) and stroke. Secondary endpoints were the safety and efficacy of the hypolipidaemic drugs as well as the cost-effectiveness of atorvastatin.
The mean dosage of atorvastatin was 24 mg/day. This statin reduced total chlesterol by 36%, LDL-C by 46%, triglycerides by 31%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 44%, while it increased HDL-C by 7%; all these changes were significant. The NCEP LDL-C and non-HDL-C treatment goals were reached by 95% (n = 759) and 97% (n = 776), respectively, of patients on atorvastatin. Only 14% of the 'usual' care patients received any hypolipidaemic drugs throughout the study and 3% of them reached the NCEP LDL-C treatment goal. The cost per quaility-adjusted life-year gained with atorvastatin was estimated at $US 8350. During this study 196 (24.5%) CHD patients on 'usual' care had a CHD recurrent event or died vs. 96 (12%) CHD patients on atorvastatin; risk ratio (RR) 0.49, confidence interval (CI) 0.27-0.73, p < 0.0001. In detail, atorvastatin reduced, in comparison to 'usual' care, total mortality (RR 0.57, CI 0.39-0.78, p = 0.0021), coronary mortality (RR 0.53, CI 0.29-0.74, p = 0.0017), coronary morbidity (RR 0.46, CI 0.25-0.71, p < 0.0001), and stroke (RR 0.53, CI 0.30-0.82, p = 0.034). All subgroups of patients (women, those with diabetes mellitus, arterial hypertension, age 60 to 75 years, congestive heart failure, recent unstable angina or prior revascularisation) benefited from treatment with atorvastatin. Withdrawal of patients because of side-effects from the atorvastatin group was low (0.75%) and similar to that of the 'usual' care group (0.4%).
Long-term treatment of CHD patients with atorvastatin to achieve NCEP lipid targets significantly reduces total and coronary mortality, coronary morbidity and stroke, in comparison to patients receiving 'usual' medical care. Treatment with atorvastatin is well tolerated and cost-effective.
阿托伐他汀在降低血浆低密度脂蛋白胆固醇（LDL-C）水平方面非常有效。然而，尚无评估这种他汀类药物的长期生存研究。
患者-方法：为评估阿托伐他汀对已确诊冠心病（CHD）患者的发病率和死亡率（总死亡率和冠心病死亡率）的影响，1600例连续患者被随机分为阿托伐他汀组或接受“常规”医疗护理组。阿托伐他汀的剂量从10mg/天滴定至80mg/天，以达到美国国家胆固醇教育计划（NCEP）规定的LDL-C<100mg/dl（2.6mmol/l）的目标。所有患者平均随访3年。
该研究的主要终点定义为死亡、非致死性心肌梗死、不稳定型心绞痛、充血性心力衰竭、血运重建（冠心病发病率）和中风。次要终点为降血脂药物的安全性和有效性以及阿托伐他汀的成本效益。
阿托伐他汀的平均剂量为24mg/天。这种他汀类药物使总胆固醇降低36%，LDL-C降低46%，甘油三酯降低31%，非高密度脂蛋白胆固醇（non-HDL-C）降低44%，同时使高密度脂蛋白胆固醇（HDL-C）升高7%；所有这些变化均具有显著性。接受阿托伐他汀治疗的患者中，分别有95%（n = 759）和97%（n = 776）达到了NCEP的LDL-C和non-HDL-C治疗目标。在整个研究过程中，“常规”护理组只有14%的患者接受了任何降血脂药物治疗，其中3%的患者达到了NCEP的LDL-C治疗目标。使用阿托伐他汀每获得一个质量调整生命年的成本估计为8350美元。在这项研究中，接受“常规”护理的196例（24.5%）冠心病患者发生了冠心病复发事件或死亡，而接受阿托伐他汀治疗的冠心病患者为96例（12%）；风险比（RR）为0.49，置信区间（CI）为0.27 - 0.73，p<0.0001。详细而言，与“常规”护理相比，阿托伐他汀降低了总死亡率（RR 0.57，CI 0.39 - 0.78，p = 0.0021）、冠心病死亡率（RR 0.53，CI 0.29 - 0.74，p = 0.0017）、冠心病发病率（RR 0.46，CI 0.25 - 0.71，p<0.0001）和中风（RR 0.53，CI 0.30 - 0.82，p = 0.034）。所有患者亚组（女性、糖尿病患者、动脉高血压患者、60至75岁患者、充血性心力衰竭患者、近期不稳定型心绞痛患者或既往血运重建患者）均从阿托伐他汀治疗中获益。阿托伐他汀组因副作用而退出治疗的患者比例较低（0.75%），与“常规”护理组（0.4%）相似。
与接受“常规”医疗护理的患者相比，用阿托伐他汀对冠心病患者进行长期治疗以达到NCEP血脂目标可显著降低总死亡率和冠心病死亡率、冠心病发病率及中风发生率。阿托伐他汀治疗耐受性良好且具有成本效益。
