Shepherd James, Blauw Gerard J, Murphy Michael B, Bollen Edward L E M, Buckley Brendan M, Cobbe Stuart M, Ford Ian, Gaw Allan, Hyland Michael, Jukema J Wouter, Kamper Adriaan M, Macfarlane Peter W, Meinders A Edo, Norrie John, Packard Chris J, Perry Ivan J, Stott David J, Sweeney Brian J, Twomey Cillian, Westendorp Rudi G J
University Department of Pathological Biochemistry, University of Glasgow, Royal Infirmary, Scotland, Glasgow, UK.
Lancet. 2002 Nov 23;360(9346):1623-30. doi: 10.1016/s0140-6736(02)11600-x.
Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke.
We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat.
Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability.
Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.
尽管他汀类药物可降低中年个体的冠心病和脑血管疾病的发病率及死亡率，但其在老年人中的疗效和安全性尚未完全明确。我们的目的是在患有心血管疾病或有发生心血管疾病及中风高风险的老年男性和女性队列中，测试普伐他汀治疗的益处。
我们进行了一项随机对照试验，将5804名年龄在70 - 82岁、有血管疾病病史或危险因素的男性（n = 2804）和女性（n = 3000）随机分为普伐他汀组（每日40毫克；n = 2891）或安慰剂组（n = 2913）。基线胆固醇浓度范围为4.0 mmol/L至9.0 mmol/L。平均随访3.2年，我们的主要终点是冠心病死亡、非致死性心肌梗死以及致死性或非致死性中风的复合终点。分析采用意向性分析。
普伐他汀使低密度脂蛋白胆固醇浓度降低了34%，主要终点事件的发生率降至408例，而安慰剂组为473例（风险比0.85，95%可信区间0.74 - 0.97，p = 0.014）。冠心病死亡和非致死性心肌梗死风险也降低了（0.81，0.69 - 0.94，p = 0.006）。中风风险未受影响（1.03，0.81 - 1.31，p = 0.8），但短暂性脑缺血发作的风险比为0.75（0.55 - 1.00，p = 0.051）。普伐他汀组新诊断出癌症的情况比安慰剂组更频繁（1.25，1.04 - 1.51，p = 0.020）。然而，将这一发现纳入所有普伐他汀和所有他汀类药物试验的荟萃分析中，并未显示总体风险增加。普伐他汀组冠心病死亡率下降了24%（p = 0.043）。普伐他汀对认知功能或残疾无显著影响。
给予普伐他汀3年可降低老年人患冠心病的风险。因此，PROSPER研究将目前用于中年人的治疗策略扩展到了老年人。
