Alharbi Fawaz F, Kholod Anzhelika A V, Souverein Patrick C, Meyboom Ronald H, de Groot Mark C H, de Boer Anthonius, Klungel Olaf H
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80 082, 3508 TB, Utrecht, The Netherlands.
Division of Laboratory and Pharmacy, Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands.
Fundam Clin Pharmacol. 2017 Dec;31(6):676-684. doi: 10.1111/fcp.12313. Epub 2017 Sep 5.
The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting.
本研究的目的是评估年龄和性别对与肾素-血管紧张素系统（RAS）抑制剂相关的咳嗽和血管性水肿报告的影响。在药物不良反应数据库（VigiBase）中进行了病例/非病例研究。确定了两个病例组，即咳嗽报告组和血管性水肿报告组，非病例为所有其他不良事件的报告。采用逻辑回归分析评估按年龄/性别分层的各类RAS抑制剂与咳嗽和血管性水肿报告之间的关联，并控制混杂因素。使用血管紧张素转换酶（ACE）抑制剂时，女性咳嗽报告率显著高于男性[校正报告比值比（ROR）：女性为44.0，95%置信区间（43.2 - 44.8）；男性为29.2，95%置信区间（28.5 - 29.9）]。与血管紧张素受体阻滞剂（ARB）和阿利吉仑相关的咳嗽报告在男性和女性之间没有差异。相比之下，使用ACE抑制剂和ARB时，男性血管性水肿报告率显著高于女性，但对于阿利吉仑，女性的校正ROR显著高于男性[校正ROR：女性为5.20，95%置信区间（4.18 - 6.46）；男性为3.04，95%置信区间（2.30 - 4.02）]。使用ACE抑制剂时，咳嗽报告率随年龄增加，直至中年（40 - 59岁）达到平稳，而使用ACE抑制剂时，血管性水肿报告率随年龄增加，直至老年（60 - 79岁）。年龄对使用ARB和阿利吉仑时咳嗽和血管性水肿报告的影响较小。年龄和性别对RAS抑制剂尤其是ACE抑制剂相关的咳嗽和血管性水肿报告均有显著影响。需要进一步研究以确定这些差异主要是在亚组中表现出不同的药物不良反应风险，还是也可以由影响报告的因素来解释。
