库尼斯综合征：对世界卫生组织国际药物警戒数据库中个体病例安全报告的回顾性分析

Kounis syndrome: A retrospective analysis of individual case safety reports from the international WHO database in pharmacovigilance .

作者信息

Orion Klaus, Mack Jochen, Kullak-Ublick Gerd A, Weiler Stefan

出版信息

Int J Clin Pharmacol Ther. 2019 May;57(5):240-248. doi: 10.5414/CP203344.

DOI:10.5414/CP203344

PMID:30900982

Abstract

OBJECTIVE

Kounis syndrome (KS) is an acute coronary syndrome with coronary spasm, acute myocardial infarction and stent thrombosis that can be associated with a variety of drugs as an adverse drug reaction (ADR). To characterize this rare phenomenon, we analyzed all cases of KS in the WHO database for pharmacovigilance.

MATERIALS AND METHODS

All cases of KS worldwide until December 31, 2017, were included and analyzed in terms of age, sex, country, year of ADR, seriousness, clinical outcome, suspected drugs, administration, reported reaction, and -MedDRA terms. Time to onset of the ADR was calculated, and a subgroup analysis of KS associated with analgesics was performed. IC025 values were calculated for the most frequently reported pain medication to indicate the strength of relation between ADR and the suspected analgesics.

RESULTS

A total of 403 cases of KS reported from 17 countries were included, of which 121 cases were associated with analgesics (subgroup). Males were more frequently affected overall (267 (66%) males vs. 123 (31%) females), whereas in the subgroup, males and females were equally affected (58 (48%) males vs. 56 (46%) females). Median reported patient age was 57 years (range 2 - 99) overall vs. 48 years (range 20 - 85) in the subgroup. Nearly all cases were classified as serious (370 (92%) overall vs. 119 (98%) subgroup). The most frequently suspected substance was amoxicillin/clavulanic acid (n = 50, 9.3%) overall and ibuprofen (n = 33, 6.2%) in the subgroup, respectively. Most drugs were administered orally (21% overall vs. 21% subgroup) and intravenously (18.7% overall vs. 8% subgroup) in either group. A high proportion of patients with "life threatening" reactions received intravenous administration (37%) of the suspected drug.

CONCLUSION: Antibiotics and analgesics are the drug classes most often associated with KS. The way of administration might have an influence on the seriousness of the reaction. .

摘要

目的

库尼氏综合征（KS）是一种伴有冠状动脉痉挛、急性心肌梗死和支架血栓形成的急性冠状动脉综合征，可作为药物不良反应（ADR）与多种药物相关。为了描述这种罕见现象，我们分析了世界卫生组织药物警戒数据库中的所有KS病例。

材料与方法

纳入截至2017年12月31日全球范围内的所有KS病例，并从年龄、性别、国家、ADR发生年份、严重程度、临床结局、可疑药物、给药方式、报告的反应以及医学术语词典（MedDRA）术语等方面进行分析。计算ADR的发病时间，并对与镇痛药相关的KS进行亚组分析。计算最常报告的止痛药物的IC025值，以表明ADR与可疑镇痛药之间的关联强度。

结果

共纳入了来自17个国家报告的403例KS病例，其中121例与镇痛药有关（亚组）。总体上男性受影响更频繁（男性267例（66%）对女性123例（31%）），而在亚组中，男性和女性受影响程度相同（男性58例（48%）对女性56例（46%））。总体报告的患者中位年龄为57岁（范围2 - 99岁），亚组中为48岁（范围20 - 85岁）。几乎所有病例都被归类为严重（总体370例（92%）对亚组119例（98%））。总体上最常怀疑的物质是阿莫西林/克拉维酸（n = 50，9.3%），亚组中是布洛芬（n = 33，6.2%）。两组中大多数药物通过口服给药（总体21%对亚组21%）和静脉给药（总体18.7%对亚组8%）。高比例有“危及生命”反应的患者接受了可疑药物的静脉给药（37%）。