中风后停用Statin会增加死亡与需依赖照顾风险

　　August 30, 2007 — 研究显示，缺血性中风住院之后停止statin治疗者，死亡风险将增加5倍，3个月内再度中风风险也会增加。
　　
　　此外，急性中风期间停止statin治疗的病患，早期神经恶化(END)风险将增加9倍，且梗塞范围更大。
　　
　　该项研究的主要作者，西班牙圣地牙哥大学的Jose Castillo医师在美国神经医学会中发表声明指出，这些结果强烈建议医师应对缺血性中风病患持续使用statin药物。
　　
　　Castillo医师表示，没有任何规范建议病患在中风后停用 statin，有许多案例为了避免气管异物堵塞而停用该药物，特别是极严重中风者；他表示，该项研究显示继续使用statin会有帮助。
　　
　　这项研究发表于8月28日的神经学( Neurology)期刊。
　　
　　这个单一中心分析包括了2003年10月到2005年5月之间，215 位急性脑梗塞缺血性中风发作后24小时内住院的病患。
　　
　　在这些人中，有89 位原本使用statin治疗者，随机接受每天 20 mg 的atorvastatin (经由口服或者经由鼻胃管)， 或者在中风之后3天停止使用statin。
　　
　　住院之前未使用statin治疗的病患，则当作次级分析的对照组。
　　
　　从第4天之后，也给予停用组和对照组每天20 mg 的atorvastatin。
　　
　　【更大的梗塞范围】
　　初步结果是3个月时死亡或需依赖照顾，定义是改良式Rankin中风等级(modified Rankin Scale)大于2，次级结果是梗塞面积和END，定义是在住院到住院后48小时内发生“美国国家卫生研究院中风量表(National Institutes of Health Stroke Scale,NIHSS)分数”增加4分以上。
　　
　　3个月后，停用statin组中，60% (27) 不是死亡就是需要依赖照护，而继续使用statin治疗者则是39% (16)。
　　
　　停用Statin 而死亡或需依赖照护之校正风险

停用 Statin 组 , n (%)	风险比	95% CI
27 (60)	4.66	1.46 – 14.91

　　再者，停用statin组有65.2% (30) 病患、未停用statin组有20.9% (9) 发现有END；作者也指出，停用statin组的梗塞面积大于继续使用statin治疗者。
　　
　　此外，次级分析发现对照组的心房纤维颤动频率比较高，而相较于和随机组病患，较没有先前的高胆固醇血症病史。
　　
　　【Statin治疗不应中断】
　　事后分析显示，停用组和对照组之间的初级结果没有差异；不过，研究者观察到，停用statin治疗组的病患的END风险比对照组高19倍。
　　
　　根据作者表示，之前的动物和临床研究显示，statin的神经保护效果，与降低血浆胆固醇以及透过过度表现一氧化氮合成而直接改善内皮功能有关，另外还有抗血栓和抗发炎效果。
　　
　　而statin对缺血性中风的神经保护作用之适当剂量仍未知，脑缺血的动物研究显示低剂量即可以有神经保护作用。
　　
　　他们指出，其发现强烈支持之前的statin研究，不应在缺血中风急性期中断此药；建议在发生缺血中风之后立即开始使用statin，但这需要更进一步的随机试验。
　　
　　这项研究部分受西班牙健康部资金赞助，Castillo医师和共同作者Jose Vivancos医师、Antonio Davalo医师都是辉瑞药厂的科学顾问；其他研究作者没有相关利益冲突。

 

Stopping Statins After Stroke Raises Risk for Death, Dependence

By Caroline Cassels
Medscape Medical News

August 30, 2007 — Individuals who stop statin treatment after hospitalization for ischemic stroke have nearly a 5-fold increased risk for death or dependence within 3 months poststroke, a new study suggests.

In addition, patients who are withdrawn from statin therapy during the acute phase of stroke have almost a 9-fold increased risk for early neurologic deterioration (END) and larger infarct volumes.

"These results strongly support the recommendation to physicians to continue statin drugs during the acute phase of an ischemic stroke," the study's principal investigator, José Castillo, MD, PhD, from the University of Santiago de Compostela, in Santiago, Spain, said in a statement from the American Academy of Neurology.

Dr. Castillo added that while no protocols suggest patients should not receive statins after stroke, in many cases the drugs are discontinued to avoid bronchoaspiration, particularly in the most severe strokes. "This study clearly shows the benefits of continuing statin use," he said.

The study is published in the August 28 issue of Neurology.

The single-center analysis included 215 consecutive patients hospitalized for acute hemispheric ischemic stroke and admitted within 24 hours of symptom onset from October 2003 to May 2005.

Of these, 89 subjects who were on previous statin therapy were randomized to receive 20 mg daily of atorvastatin (administered orally or through a nasogastric tube) or were taken off statins for 3 days immediately following stroke.

Patients who had not been on statin therapy prior to admission were followed up as a reference group for secondary analysis.

From the fourth day onward, atorvastatin 20 mg daily was also administered to patients in the withdrawal group and in those who were not on previous statin treatment.

Greater Infarct Volume

The primary outcome was death or dependence at 3 months, defined as a modified Rankin Scale of greater than 2. Secondary outcomes were infarct volume and END, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of 4 points or more between time of admission and any time during the first 48 hours of hospitalization.

After 3 months, 60% (27) of those in the statin-withdrawal group had either died or were disabled to the point of dependence compared with 39% (16) of those who had continuous statin therapy.

Adjusted Risk for Death or Dependence Associated With Statin Withdrawal

Statin-Withdrawal Group, n (%)	Odds Ratio	95% CI
27 (60)	4.66	1.46 – 14.91

Furthermore, END was found in 65.2% (30) of patients in the statin-withdrawal group vs 20.9% (9) of the non–statin-withdrawal subjects. The authors also report that infarct volume was greater in statin-withdrawal patients compared with those who remained on statin therapy.

In addition, secondary analysis revealed patients in the reference group had a higher frequency of atrial fibrillation and were less likely to have a previous history of hypercholesterolemia than randomized patients.

Statin Therapy Should Not Be Interrupted

Post hoc analysis showed no difference in the study's primary outcome among the statin-withdrawal group and the reference group. However, the researchers observed a 19-fold increased risk for END among patients who were withdrawn from statin therapy compared with referent subjects.

According to the authors, previous animal and clinical research has shown the neuroprotective effect of statins is related not only to the reduction of plasma cholesterol but also to their direct influence on improving endothelial function through the overexpression of nitric-oxide synthase, as well as their antithrombotic and anti-inflammatory effects.

While the optimal dose of statins for neuroprotection in ischemic stroke is not known, animal studies of cerebral ischemia indicate neuroprotection is more likely at lower doses.

"Our findings strongly support that previous statin therapy should not be interrupted during the acute phase of ischemic stroke. The recommendation to start on statin treatment as soon as ischemic stroke occurs needs to be investigated in further randomized trials," they write.

The study was partially supported by grants from the Spanish Ministry of Health. Dr. Castillo and coauthors José Vivancos, MD, PhD,and Antonio Dávalo, MD, PhD, are scientific advisors to Pfizer. The other study authors report no conflicts of interest.

Neurology. 2007;69:904-910.