未破裂颅内动脉瘤预防性治疗的候选药物：一项横断面研究。
Candidate drugs for preventive treatment of unruptured intracranial aneurysms: A cross-sectional study.
机构信息
Department of Neurosurgery, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
出版信息
PLoS One. 2021 Feb 12;16(2):e0246865. doi: 10.1371/journal.pone.0246865. eCollection 2021.
BACKGROUND AND PURPOSE
Establishment of drug therapy to prevent rupture of unruptured intracranial aneurysms (IAs) is needed. Previous human and animal studies have gradually clarified candidate drugs for preventive treatment of IA rupture. However, because most of these candidates belong to classes of drugs frequently co-administered to prevent cardiovascular diseases, epidemiological studies evaluating these drugs simultaneously should be performed. Furthermore, because drugs included in the same class may have different effects in terms of disease prevention, drug-by-drug assessments are important for planning intervention trials.
MATERIALS AND METHODS
We performed a cross-sectional study enrolling patients diagnosed with IAs between July 2011 and June 2019 at our institution. Patients were divided into ruptured or unruptured groups. The drugs investigated were selected according to evidence suggested by either human or animal studies. Univariate and multivariate logistic regression analyses were performed to assess the association of drug treatment with rupture status. We also performed drug-by-drug assessments of the association, including dose-response relationships, with rupture status.
RESULTS
In total, 310 patients with ruptured and 887 patients with unruptured IAs were included. Multivariate analysis revealed an inverse association of statins (odds ratio (OR), 0.54; 95% confidence interval (CI) 0.38-0.77), calcium channel blockers (OR, 0.41; 95% CI 0.30-0.58), and angiotensin II receptor blockers (ARBs) (OR, 0.67; 95% CI 0.48-0.93) with ruptured IAs. Moreover, inverse dose-response relationships with rupture status were observed for pitavastatin and rosuvastatin among statins, benidipine, cilnidipine, and amlodipine among calcium channel blockers, and valsartan, azilsartan, candesartan, and olmesartan among ARBs. Only non-aspirin non-steroidal anti-inflammatory drugs were positively associated with ruptured IAs (OR, 3.24; 95% CI 1.71-6.13).
CONCLUSIONS
The present analysis suggests that several types of statins, calcium channel blockers, and ARBs are candidate drugs for preventive treatment of unruptured IAs.
背景与目的
需要建立药物治疗来预防未破裂颅内动脉瘤（IAs）的破裂。以前的人类和动物研究逐渐阐明了候选药物用于预防 IA 破裂。然而，由于大多数这些候选药物属于经常联合用于预防心血管疾病的药物类别，因此应进行同时评估这些药物的流行病学研究。此外，由于同一类药物在预防疾病方面可能具有不同的效果，因此对每种药物进行评估对于规划干预试验很重要。
材料与方法
我们进行了一项横断面研究，纳入了 2011 年 7 月至 2019 年 6 月期间在我院诊断为 IAs 的患者。患者分为破裂组和未破裂组。根据人类或动物研究提供的证据选择研究药物。进行单变量和多变量逻辑回归分析，以评估药物治疗与破裂状态的关联。我们还对每种药物与破裂状态的关联进行了药物评估，包括剂量-反应关系。
结果
共纳入 310 例破裂性和 887 例未破裂性 IAs 患者。多变量分析显示他汀类药物（比值比（OR），0.54；95%置信区间（CI），0.38-0.77）、钙通道阻滞剂（OR，0.41；95%CI，0.30-0.58）和血管紧张素 II 受体阻滞剂（ARB）（OR，0.67；95%CI，0.48-0.93）与破裂性 IAs 呈负相关。此外，在他汀类药物中，发现匹伐他汀和罗苏伐他汀与破裂状态呈负相关剂量-反应关系，在钙通道阻滞剂中，发现贝尼地平、西尼地平、氨氯地平与破裂状态呈负相关剂量-反应关系，在 ARBs 中，发现缬沙坦、阿齐沙坦、坎地沙坦和奥美沙坦与破裂状态呈负相关剂量-反应关系。只有非阿司匹林非甾体抗炎药与破裂性 IAs 呈正相关（OR，3.24；95%CI，1.71-6.13）。
结论
本分析表明，几种类型的他汀类药物、钙通道阻滞剂和 ARB 可能是预防未破裂 IAs 的候选药物。
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