Rydberg Diana M, Mejyr Stefan, Loikas Desirée, Schenck-Gustafsson Karin, von Euler Mia, Malmström Rickard E
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Clinical Pharmacology, Drug Evaluation Unit, L7:03, Karolinska University Hospital Solna, 17176, Stockholm, Sweden.
Eur J Clin Pharmacol. 2018 Sep;74(9):1165-1173. doi: 10.1007/s00228-018-2480-y. Epub 2018 May 27.
To explore sex differences in spontaneously reported adverse drug events (ADEs) for antihypertensives in routine care.
A cross sectional analysis combining number of reports from the national pharmacovigilance database with data from the Swedish Prescribed Drug Register, from 2005 to 2012 for ACE inhibitors (ACE-I) and angiotensin receptor blockers (ARB), with or without thiazide, diuretics (thiazides, potassium-sparing agents, sulfonamides, aldosterone antagonists), selective betablockers, and dihydropyridine calcium-channel-blockers (DHPs). The total number of reports was adjusted to exposed patients and dispensed DDDs among women and men. Dose exposures, co-medications, and co-prescriptions were also analyzed.
In women, a higher prevalence of ADE-reports was seen in ACE-I (odds ratio, OR 1.21; 95% CI 1.09-1.35), ACE-I-combinations (OR 1.61; 1.44-1.79), ARB-combinations (OR 2.12; 1.47-3.06), thiazides (OR 1.78; 1.33-2.39), diuretics and potassium-sparing agents (OR 1.62; 1.22-2.17), and DHPs (OR 1.40; 1.17-1.67), with a potential linkage to dose exposure. For aldosterone antagonists, we observed a higher prevalence of ADE reports in men (OR 0.75; 0.59-0.97) but without any sex difference in dose exposure.
This ecological study of reported ADEs showed a higher prevalence of reports in women in six out of ten groups of antihypertensive drugs, and this may potentially be linked to dose exposure. Aldosterone antagonists was the only group with a higher prevalence of ADE-reports in men with a similar dose exposure between women and men.
探讨常规治疗中抗高血压药物自发报告的不良药物事件（ADEs）的性别差异。
采用横断面分析，将国家药物警戒数据库的报告数量与瑞典处方药登记处2005年至2012年期间关于含或不含噻嗪类的血管紧张素转换酶抑制剂（ACE-I）和血管紧张素受体阻滞剂（ARB）、利尿剂（噻嗪类、保钾剂、磺胺类、醛固酮拮抗剂）、选择性β受体阻滞剂和二氢吡啶类钙通道阻滞剂（DHPs）的数据相结合。报告总数根据女性和男性中暴露患者及配发的限定日剂量（DDD）进行了调整。还分析了剂量暴露、合并用药和联合处方情况。
在女性中，ACE-I（优势比，OR 1.21；95%可信区间1.09 - 1.35）、ACE-I联合用药（OR 1.61；1.44 - 1.79）、ARB联合用药（OR 2.12；1.47 - 3.06）、噻嗪类（OR 1.78；1.33 - 2.39）、利尿剂和保钾剂（OR 1.62；1.22 - 2.17）以及DHPs（OR 1.40；1.17 - 1.67）的ADE报告患病率较高，且可能与剂量暴露有关。对于醛固酮拮抗剂，我们观察到男性的ADE报告患病率较高（OR 0.75；0.59 - 0.97），但在剂量暴露方面无性别差异。
这项关于报告的ADEs的生态学研究表明，在十组抗高血压药物中有六组女性的报告患病率较高，这可能与剂量暴露有关。醛固酮拮抗剂是唯一一组男性的ADE报告患病率较高且男女剂量暴露相似的药物。
