Waters David D, LaRosa John C, Barter Philip, Fruchart Jean-Charles, Gotto Antonio M, Carter Roddy, Breazna Andrei, Kastelein John J P, Grundy Scott M
University of California, San Francisco, California, USA.
J Am Coll Cardiol. 2006 Nov 7;48(9):1793-9. doi: 10.1016/j.jacc.2006.07.041. Epub 2006 Oct 17.
We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl.
Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated.
We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years.
Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment.
Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).
我们试图评估将稳定型冠心病患者的低密度脂蛋白胆固醇（LDL-C）水平大幅降至100mg/dl以下对脑血管事件的影响。
他汀类药物降低LDL-C已被证明可降低稳定型冠心病患者的中风风险。在观察性研究中，自然低胆固醇水平与出血性中风风险增加有关。此前尚未研究将稳定型冠心病患者的LDL-C水平大幅降至100mg/dl以下的脑血管益处。
我们描述了在强化降脂治疗新目标（TNT）研究中对脑血管事件的分析，该试验将10001例有冠心病记录的患者随机分为接受10mg/日或80mg/日阿托伐他汀治疗，并随访中位时间4.9年。
10mg阿托伐他汀治疗组的平均LDL-C水平为101mg/dl，80mg组为77mg/dl。除了主要心血管事件减少（风险比0.78，95%置信区间[CI]0.69至0.89；p = 0.0002），该试验的主要终点，80mg组患者的脑血管事件减少（风险比0.77，95%CI 0.64至0.93；p = 0.007），中风减少（风险比0.75，95%CI 0.59至0.96；p = 0.02）。治疗使LDL-C每降低1mg/dl与脑血管事件相对风险降低0.6%（p = 0.002）和中风相对风险降低0.5%（p = 0.041）相关。80mg组和10mg组的出血性中风发生率相似，分别为16例和18例，且出血性中风在治疗期间达到的LDL-C五分位数中分布均匀。
在已确诊冠心病的患者中，与10mg/日剂量相比，使用80mg/日阿托伐他汀将LDL胆固醇大幅降至100mg/dl以下可使中风和脑血管事件再减少20%至25%。在低LDL-C水平未观察到出血性中风增加。（强化降脂治疗新目标；http://www.clinicaltrials.gov；NCT00327691）
