Division of Cardiology, San Francisco General Hospital, and the Department of Medicine, University of California, San Francisco, CA, USA.
J Cardiol. 2010 Mar;55(2):155-62. doi: 10.1016/j.jjcc.2009.12.003. Epub 2010 Jan 7.
Statins have been shown to reduce cardiovascular events across a broad spectrum of patients at risk, irrespective of baseline LDL-cholesterol levels. In a meta-analysis of 14 statin trials involving more than 90,000 participants, statin therapy reduced the 5-year incidence of cardiovascular events by about 20% for each mmol/L of LDL-cholesterol reduction. The results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study suggest that the degree of reduction in Japanese subjects may be greater than this for the same degree of LDL-cholesterol reduction. Given the success of statins in preventing cardiovascular events, it is not surprising that they have been tested in a variety of related conditions, three of which are discussed in this article. Heart failure is characterized by inflammation, endothelial dysfunction and neurohumeral activation, conditions that are ameliorated by statin therapy. The Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) showed no significant benefit of rosuvastatin upon the primary endpoint, cardiovascular death, myocardial infarction and stroke. However, subgroups identified by the biomarkers plasma amino-terminal pro-brain natriuretic and C-reactive protein showed a reduction in events. Aortic stenosis and atherosclerosis share common risk factors, including hypertension and hypercholesterolemia. Although non-randomized cohort studies have suggested that statins slow the progression of aortic stenosis, this was not shown in either of the two randomized placebo-controlled trials testing this hypothesis. Similarly, Alzheimer's disease shares many risk factors with atherosclerosis, and several observational studies have reported a lower risk of developing this condition in patients taking statins. However, two recently completed clinical trials indicate that neither atorvastatin nor simvastatin slow the progression of early Alzheimer's disease. In conclusion, although statins are effective, established therapy for the prevention of vascular events in patients at risk, they have as yet not proven to be successful for these newer indications.
他汀类药物已被证明可降低各种风险患者的心血管事件发生率，而与基线 LDL 胆固醇水平无关。在一项涉及超过 90,000 名参与者的 14 项他汀类药物试验的荟萃分析中，他汀类药物治疗使 LDL 胆固醇降低每 mmol/L 可使心血管事件的 5 年发生率降低约 20%。管理成年人日本人升高胆固醇的主要预防组（MEGA）研究的结果表明，与 LDL 胆固醇降低相同程度的日本人降低幅度可能更大。鉴于他汀类药物在预防心血管事件方面的成功，它们在各种相关疾病中的测试并不令人惊讶，本文讨论了其中三种疾病。心力衰竭的特征是炎症、内皮功能障碍和神经激素激活，这些情况通过他汀类药物治疗得到改善。控制瑞舒伐他汀多国心力衰竭试验（CORONA）表明，瑞舒伐他汀对主要终点，即心血管死亡、心肌梗死和中风，没有显著益处。然而，通过生物标志物血浆氨基末端脑钠肽和 C 反应蛋白确定的亚组显示出事件减少。主动脉瓣狭窄和动脉粥样硬化具有共同的危险因素，包括高血压和高胆固醇血症。尽管非随机队列研究表明他汀类药物可减缓主动脉瓣狭窄的进展，但这在两项测试这一假说的随机安慰剂对照试验中均未得到证明。同样，阿尔茨海默病与动脉粥样硬化有许多共同的危险因素，几项观察性研究报告称，服用他汀类药物的患者患这种疾病的风险较低。然而，最近完成的两项临床试验表明，阿托伐他汀或辛伐他汀均不能减缓早期阿尔茨海默病的进展。总之，尽管他汀类药物是预防高危患者血管事件的有效、既定疗法，但它们尚未被证明对这些新适应症有效。
