Josan Kiranbir, Majumdar Sumit R, McAlister Finlay A
Division of General Internal Medicine, Department of Medicine, University of Alberta, Edmonton, Alta.
CMAJ. 2008 Feb 26;178(5):576-84. doi: 10.1503/cmaj.070675.
Recent lipid guidelines recommend aggressive low-density lipoprotein (LDL) cholesterol lowering in patients with coronary artery disease. To clarify the evidence for this recommendation, we conducted a meta-analysis of randomized controlled trials that compared different intensities of statin therapy.
We searched electronic databases (MEDLINE, EMBASE, Cochrane Central Registery of Controlled Trials, Web of Science) for randomized controlled trials published up to July 19, 2007, that compared statin regimens of different intensities in adults with coronary artery disease and that reported cardiovascular events or mortality. Data were pooled using random-effects models to calculate odds ratios (OR).
A total of 7 trials (29 395 patients) were included. Compared with less intensive statin regimens, more intensive regimens further reduced LDL levels (0.72 mmol/L reduction, 95% confidence interval [CI] 0.60-0.84 mmol/L), and reduced the risk of myocardial infarction (OR 0.83, 95% CI 0.77-0.91) and stroke (OR 0.82, 95% CI 0.71-0.95). Although there was no effect on mortality among patients with chronic coronary artery disease (OR 0.96, 95% CI 0.80-1.14), all-cause mortality was reduced among patients with acute coronary syndromes treated with more intensive statin regimens (OR 0.75, 95% CI 0.61-0.93). Compared with lower intensity regimens, more intensive regimens were associated with small absolute increases in rates of drug discontinuation (2.5%), elevated levels of aminotransferases (1%) and myopathy (0.5%), and there was no difference in noncardiovascular mortality. All 7 trials reported events by randomization arm rather than by LDL level achieved. About half of the patients treated with more intensive statin therapy did not achieve an LDL level of less than 2.0 mmol/L, and none of the trials tested combination therapies.
Our analysis supports the use of more intensive statin regimens in patients with established coronary artery disease. There is insufficient evidence to advocate treating to particular LDL targets, using combination lipid-lowering therapy to achieve these targets or for using more intensive regimens in patients without established coronary artery disease.
近期的血脂指南建议对冠心病患者积极降低低密度脂蛋白（LDL）胆固醇水平。为明确这一建议的证据，我们对比较不同强度他汀类药物治疗的随机对照试验进行了荟萃分析。
我们检索了电子数据库（MEDLINE、EMBASE、Cochrane对照试验中心注册库、科学引文索引），以查找截至2007年7月19日发表的随机对照试验，这些试验比较了冠心病成年患者不同强度的他汀类药物治疗方案，并报告了心血管事件或死亡率。使用随机效应模型汇总数据以计算比值比（OR）。
共纳入7项试验（29395例患者）。与强度较低的他汀类药物治疗方案相比，强度较高的方案进一步降低了LDL水平（降低0.72 mmol/L，95%置信区间[CI] 0.60 - 0.84 mmol/L），并降低了心肌梗死风险（OR 0.83，95% CI 0.77 - 0.91）和中风风险（OR 0.82，95% CI 0.71 - 0.95）。虽然对慢性冠心病患者的死亡率没有影响（OR 0.96，95% CI 0.80 - 1.14），但接受强度较高他汀类药物治疗方案的急性冠脉综合征患者的全因死亡率降低（OR 0.75，95% CI 0.61 - 0.93）。与较低强度方案相比，强度较高的方案与停药率（2.5%）、转氨酶水平升高（1%）和肌病（0.5%）的绝对小幅增加相关，且非心血管死亡率无差异。所有7项试验按随机分组而非达到的LDL水平报告事件。接受强度较高他汀类药物治疗的患者中约有一半未达到LDL水平低于2.0 mmol/L，且没有试验测试联合治疗。
我们的分析支持在已确诊冠心病的患者中使用强度较高的他汀类药物治疗方案。没有足够的证据支持针对特定的LDL目标进行治疗、使用联合降脂疗法来实现这些目标或在未确诊冠心病的患者中使用强度较高的方案。
