积极降低血脂肪可以降低中风发生率

　　Dec. 1, 2005（达拉斯讯）－根据研究者于美国心脏医学会2005年科学座谈发表的研究报告，积极降低血脂肪可以降低心脏疾病，以及中风的风险。
　　
　　加州旧金山郡立医院David Waters医师表示，脑血管疾病对statins类药物的反应，就跟冠状血管事件一样，例如心脏病发或是心绞痛；降低中风发生率是使用statins类药物或是类似这项试验中的族群一样使用高剂量statin的另一个理由。
　　
　　根据the Treating to New Targets（TNT）试验的研究者表示，相较于使用较低剂量，以每天80毫克atrovastatin积极地降低血脂肪，可以降低23%致命与非致命脑血管事件、及25%中风的发生率；然而，降低短暂性缺血性发作（TIAs）发生率的效果并未达到统计上的差异。
　　
　　Waters医师表示，然而，合并冠状动脉血管疾病相关的死亡、非致命性心肌梗塞、需要复苏的心脏停止、或是中风的初级试验终点，每天使用10毫克atrovastatin的病患为10.9%，相较于每天使用80毫克病患的8.7%；绝对风险下降为2.2%、换算为相对风险下降为22%（P＝.0002)，这些结果之前已于3月号的新英格兰医学期刊发表。
　　
　　Waters医师表示，对于冠状动脉心血管疾病病患而言，许多其他的临床试验已经证实，相对于安慰剂，statin类药物可以降低脑血管疾病的风生率；但是这是第一个比较相同药物的不同剂量，而且证实高剂量效果较佳的试验。
　　
　　这项试验为TNT试验中10,001位稳定性冠状动脉血管疾病病患的后续分析，主要是针对脑血管疾病发生率；这项试验中的病患被随机分派接受每天80或是10毫克的atrovastatin，之后追踪5年；临床试验终点包括发生第一次脑血管疾病的时间、发生第一次中风的时间、以及发生第一次TIA的时间；脑血管事件、任何病因引发的中风、已经出血性中风以低密度脂蛋白（LDL－C）浓度的四分位数来分级。
　　
　　治疗前，病患的LDL－C从130 mg/L到250 mg/L；两组病患的基本特征是差不多的，所有的病患都患有冠状动脉心血管疾病，60%病患过去曾发生心肌梗塞、5%有脑血管事件的病史。
　　
　　每天服用80毫克的atrovstatin将受试者的LDL－C降低到77 mg/L，然而每天服用10毫克atrovastatin病患的LDL－C降低到101 mg/L。
　　
　　每天服用80毫克相较于服用10毫克的atrovstatin的病患，中风发生率显著地较低（2.3%相较于3.1%；危险比为0.75；P＝.007）；TIA的发生率也从2.2%降低至1.7%，但是并未达到统计上差异；脑血管事件发生率也从5.0%降低至3.9%（危险比为0.77；P＝.007）。
　　
　　治疗后3个月的LDL－C为脑血管事件发生与否的预测因子（P＝.002）；Waters医师表示，LDL－C每降低1 mg/L，脑血管事件发生率就下降0.6%。
　　
　　这项试验包括了许多种类的中风，其中54%被分类为缺血性的、25%为栓塞性的、12%为出血性的、而9%为未知；Waters医师指出，不论是哪一种中风，每天服用80毫克atrovastatin都可以降低这些不同形式中风的发生率。
　　
　　Waters医师的结论是，降低LDL－C浓度可以改善病患的预后；每天服用80毫克的atrovastatin就是达到这个目标的其中一个办法，然而，但是我们并不建议所有病患都使用这种办法；他进一步指出，当治疗稳定性冠状动脉疾病病患时，除了降低冠状动脉事件的再发外，降低脑血管事件的发生率也应该纳入考量。
　　
　　美国心脏医学会总裁，同时也是科罗拉多大学丹佛健康科学中心，粥状动脉硬化研究主席Robert Eckel医师表示，TNT试验证实降低LDL－C不但对冠状动脉心血管疾病病患有益，对降低脑血管事件的发生率同样是有效的。
　　
　　Eckel医师表示，在表现statins类药物的作用上，结合脑血管试验终点显然是很重要的，对预防中风的作用较好，对预防TIA的效果不是很明显；尽管如此，这些试验结果支持积极降低LDL－C的做法。

Aggressive Lipid Lowering Reduces Incidence of Stroke

By Linda Little
Medscape Medical News

Dec. 1, 2005 (Dallas) — Intensive lipid lowering can not only lower the risk of heart disease, but also the risk of stroke, researchers reported here at the American Heart Association 2005 Scientific Sessions.

"Cerebrovascular events respond to statins in roughly the same way that coronary events such as heart attack or unstable angina do," said David Waters, MD, from San Francisco General Hospital in California. "The benefit for stroke reduction is another reason to use statins or high-dose statins in populations like this."

Researchers from a substudy of the Treating to New Targets (TNT) trial found that aggressive lipid lowering with 80 mg of atorvastatin reduced the risk of fatal and nonfatal cerebrovascular events by 23% and stroke by 25% compared with those treated with lower doses. While there was a reduction in the number of transient ischemic attacks (TIAs), this did not reach statistical significance.

However, for the primary outcome measure — a composite of coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke — the rate was 10.9% in the 10-mg group and 8.7% in the 80-mg group, said Dr. Waters. "This was a 2.2% absolute reduction, or a 22% relative risk reduction (P = .0002). These results previously were reported in the New England Journal of Medicine in March."

Several other studies have shown that in patients with coronary disease, statins reduce cerebrovascular events compared with placebo, Dr. Waters said, but this is the first study that compared doses of the same statin, showing benefit with the higher dose.

The study involved a post-hoc analysis of cerebrovascular events in the 10,001 TNT trial patients with stable coronary artery disease. Patients in the trial were randomized to treatment with 80 mg or 10 mg of atorvastatin and then followed for almost 5 years. Clinical end points included time to first cerebrovascular event, time to first stroke, and time to first TIA. Cerebrovascular events, strokes of any etiology, and hemorrhagic strokes were stratified and compared by quintile of achieved low-density lipoprotein cholesterol (LDL-C) levels.

Before treatment, the participants' LDL-C levels ranged from 130 mg/dL to 250 mg/dL. Baseline characteristics of the groups were well balanced. All had advanced coronary disease, with 60% having a previous myocardial infarction and 5% having a history of a cerebrovascular accident.

Treatment with 80 mg of atorvastatin lowered LDL-C levels of study participants to 77 mg/dL, while the 10-mg treatment group's LDL-C levels were only reduced to 101 mg/dL.

The incidence of stroke was lower in the 80-mg group compared with the 10-mg group (2.3% vs 3.1%; hazard ratio, .75; P = .007). There was also a reduction in TIA from 2.2% to 1.7%, but this reduction did not reach statistical significance. Cerebrovascular events were reduced from 5.0% to 3.9% (hazard ratio, .77; P = .007).

LDL-C treatment at 3 months was the predictor of cerebrovascular events (P = .002), Dr. Waters said. "Each 1 mg/dL change was associated with a 0.6% change in cerebrovascular event rate."

The study included various categories of stroke, with 54% classified as ischemic, 25% embolic, 12% hemorrhagic, and 9% classified as unknown. "For each type of stroke, the incidence was lower in the 80-mg arm," Dr. Waters pointed out.

"Lowering LDL-C improves patient outcome," Dr. Waters concluded. "Atorvastatin 80 mg is one way to do that; however, we are not suggesting that this is the only way for all patients." He further noted that the reduction in cerebrovascular events should be considered in addition to the reduction in coronary events when treating patients with stable coronary disease.

According to the designated discussant, Robert Eckel, MD, president of the American Heart Association and chairman of atherosclerosis at the University of Colorado at Denver Health Sciences Center, the TNT study shows that "lower is also better" for cerebrovascular events in patients with coronary heart disease.

"The combined cerebrovascular end point appears important in demonstrating the effect in that the strength of the relationship was modest for stroke and nonsignificant for TIA," Dr. Eckel said. "Nevertheless, these data provide more support for the more aggressive approach."

AHA 2005 Scientific Sessions: Abstract 2019. Presented Nov. 14, 2005.

Reviewed by David Good, Site Editor/Program Director, Medscape Cardiology.