Division of Clinical Pharmacy, College of Pharmacy, Ajou University, Suwon, Korea.
Pharmacotherapy. 2019 Feb;39(2):129-139. doi: 10.1002/phar.2211. Epub 2019 Jan 29.
Statins are widely used for primary and secondary prevention of cardiovascular and cerebrovascular disease. Several large randomized trials have suggested that statins might increase the risk of intracerebral hemorrhage (ICH); studies have also shown interethnic variability in responses to statins. This study aimed to determine the association between statin use and the risk of ICH in patients with hyperlipidemia among a Korean population.
Population-based, retrospective cohort study.
Korean National Health Insurance Service-National Sample Cohort database (2002-2015).
A total of 313,368 patients, aged 40-85 years, without a history of hemorrhagic stroke were included after being diagnosed with hyperlipidemia between January 2003 and December 2013 (for follow-up through December 2015). Of those, statin users were compared with nonusers by using propensity score matching in a 1:1 ratio (21,797 in each group). The study groups were matched for age, sex, Charlson Comorbidity Index score, follow-up duration, comorbidities, and concurrent medications.
The primary endpoint was occurrence of an ICH event. Secondary endpoints were mortality (all-cause, major adverse cardiovascular and cerebrovascular event related, and stroke related) and outcomes after ICH (e.g., recurrent ICH and mortality after primary ICH event). The Cox proportional hazard model was used to evaluate the ICH risk of statins. Subgroup analyses were performed based on ICH-related risk factors. During a mean follow-up period of 6.4 years, ICH occurred in 456 of the 43,594 patients (1.05%). Statin use was significantly associated with a decreased ICH risk (adjusted hazard ratio [aHR] 0.78, 95% confidence interval [CI] 0.65-0.94). Compared with nonusers, statin users showed significantly lower all-cause mortality (aHR 0.61, 95% CI 0.57-0.64), cardiovascular and cerebrovascular disease-related mortality (aHR 0.75, 95% CI 0.65-0.85), and stroke-related mortality (aHR 0.69, 95% CI 0.54-0.88). No significant differences in recurrence and mortality after an ICH event were noted between study groups.
Statin therapy was associated with a decreased ICH risk and improvements in ischemic cardiovascular and cerebrovascular outcomes in Korean patients with hyperlipidemia. Further large-scale clinical studies are needed to clarify the impact of statins on the risk of developing ICH.
他汀类药物广泛用于心血管和脑血管疾病的一级和二级预防。几项大型随机试验表明，他汀类药物可能会增加脑出血（ICH）的风险；研究还表明，他汀类药物的反应存在种族间差异。本研究旨在确定在韩国高脂血症患者中，他汀类药物的使用与 ICH 风险之间的关系。
基于人群的回顾性队列研究。
韩国国家健康保险服务-国家样本队列数据库（2002-2015 年）。
共纳入 313368 名年龄在 40-85 岁之间、无出血性中风病史的患者，这些患者在 2003 年 1 月至 2013 年 12 月期间被诊断为高脂血症（随访至 2015 年 12 月）。其中，在倾向评分匹配的情况下，将他汀类药物使用者与非使用者按 1:1 的比例进行比较（每组 21797 人）。研究组在年龄、性别、Charlson 合并症指数评分、随访时间、合并症和同时使用的药物方面进行了匹配。
主要终点是发生 ICH 事件。次要终点为死亡率（全因、主要不良心血管和脑血管事件相关、以及与卒中相关的死亡率）和 ICH 后的结果（例如，ICH 复发和首次 ICH 事件后的死亡率）。采用 Cox 比例风险模型评估他汀类药物的 ICH 风险。根据 ICH 相关危险因素进行了亚组分析。在平均 6.4 年的随访期间，43594 名患者中有 456 名（1.05%）发生 ICH。他汀类药物的使用与 ICH 风险降低显著相关（调整后的危险比[aHR]0.78，95%置信区间[CI]0.65-0.94）。与非使用者相比，他汀类药物使用者的全因死亡率（aHR 0.61，95%CI 0.57-0.64）、心血管和脑血管疾病相关死亡率（aHR 0.75，95%CI 0.65-0.85）和卒中相关死亡率（aHR 0.69，95%CI 0.54-0.88）均显著降低。两组之间 ICH 事件后的复发和死亡率无显著差异。
他汀类药物治疗与韩国高脂血症患者的 ICH 风险降低以及缺血性心血管和脑血管结局改善相关。需要进一步的大规模临床研究来阐明他汀类药物对 ICH 风险的影响。
