应用他汀与脑出血风险的关系

有关他汀的使用与脑出血风险增加的研究结果尚有争议。因此，台湾学者对使用他汀类药物的亚洲人群发生脑出血风险进行了评估，结果表明，既往无卒中病史的患者累积他汀应用与脑出血风险之间无关。另外，非高血压队列人群的风险有所增加，但研究者表示应审慎解读这一结果。相关论文4月9日在线发表于《循环》(Circulation)杂志。

研究共纳入1096547例在2005-2009年间开始接受他汀类药物治疗、无缺血性或出血性卒中史患者，平均随访时间为3.3年。根据是否是高龄(≥ 70岁)、性别和是否诊断过高血压进行分层。主要终点为因脑出血住院情况。利用Cox回归分析脑出血的危险比(HR)，并用四分位法对他汀累积剂量进行分层分析。

结果显示，校正基线疾病风险后，他汀类药物累积剂量位于最高四分位区间患者发生颅内出血的风险与位于最低四分位区间的患者相比，没有显著差异[以最低四分位累积剂量为参照，最高四分位累积剂量HR=1.06，95%可信区间(95%CI)0.94~1.19]。敏感性分析也显示相似的结果。然而，亚组分析发现，无明确高血压的他汀使用者发生颅内出血的风险更高[校正后HR=1.36 (1.11~1.67)]。

参考文献：

Chia-Hsuin Chang, et al. CIRCULATIONAHA.114.013046Published online before print April 9, 2015,doi: 10.1161/CIRCULATIONAHA.114.013046

Risk of Intracranial Hemorrhage from Statin Use in Asians: A Nationwide Cohort Study

1. Chia-Hsuin Chang1;

2. Chin-Hsien Lin2;

3. James L. Caffrey3;

4. Yen-Chieh Lee4;

5. Ying-Chun Liu5;

6. Jou-Wei Lin6*;

7. Mei-Shu Lai5

+Author Affiliations

1. 1National Taiwan University Hospital & National Taiwan University, Taipei, Taiwan

2. 2National Taiwan University Hospital, Taipei, Taiwan

3. 3University of North Texas Health Science Center, Fort Worth, TX

4. 4National Taiwan University, Taipei, Taiwan & Cathay General Hospital, Taipei, Taiwan

5. 5National Taiwan University, Taipei, Taiwan

6. 6National Taiwan University, Taipei, Taiwan & National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Taiwan

1. ↵* Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin County, Taiwan jouweilin@yahoo.com

Abstract

Background—Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a prior history of stroke.

Methods and Results—Patients initiating statin therapy between 2005 and 2009 without a prior history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥ 70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (ICD-9-CM codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio (HR) of ICH. •

The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1,096,547 statin initiators with an average follow-up of 3.3 years. The adjusted HR for ICH between the highest the lowest quartile was non-significant at 1.06 with a 95% confidence interval [CI] spanning 1.00 (0.94-1.19). Similar non-significant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted HR 1.36 [1.11-1.67]).

Conclusions—Generally, no association was observed between cumulative statin use and risk of ICH among subjects without a prior history of stroke. An increased risk was identified among the non-hypertensive cohort, but this finding should be interpreted with caution.