Mining and analysis of cardiac disorders risk signals based on adverse drug reaction monitoring data

doi:10.19803/j.1672-8629.20240296

Abstract

Abstract: Objective To mine and analyze the risk signals of adverse drug reactions (ADR) leading to cardiac disorders in the adverse drug reaction monitoring database in order to provide reference for safe and rational drug use and for research on post-marketing drug safety. Methods The ADR reports from the adverse drug reaction monitoring system database of one province collected between 2021 and 2023 were retrieved and subjected to data cleaning. The reporting odds ratio (ROR) method was employed for detection of ADR signals, and the ROR values and their 95% confidence intervals of drugs causing cardiac disorders risks were calculated. The risk signals mined were analyzed and assessed. Results A total of 72 398 ADR reports were retrieved over the past three years. After excluding duplicate and incomplete reports, 3 697 ADR reports involving the cardiovascular system were finally included in the analysis. Female patients outnumbered male ones, and ADR occurred predominantly in patients over 65 years old after medication. Diseases related to the respiratory system, mediastinal diseases, vascular and lymphatic diseases and heart diseases accounted for nearly 60% of the primary diseases. In over half of the reports, ADR occurred within less than one day of medication, and more than 60% of the ADR occurred on the very day of medication. The overall outcome of adverse reactions was favorable. Among the 263 suspected drugs analyzed, 70 risk signals of cardiac disorders were identified using the ROR method, including 62 anticipated signals documented in the package inserts and 8 unanticipated ones not documented in the package inserts. Conclusion The ROR method is generally reliable for mining and analyzing risk signals of cardiac disorders. However, the signals generated by this method are far from conclusive in that their credibility and robustness are influenced by the quantity, quality, and confounding factors of the data. In addition to focusing on drugs that may cause cardiac disorders, pharmacovigilance personnel should also take into consideration the differences between individual patients and clinical medication risk factors to minimize drug-induced cardiac risks and ensure safe medication.

Key words: adverse drug reaction, pharmacovigilance, cardiac disorders, risk signal, reporting odds ratio, rational drug use

CLC Number:

R994.11

ALATENG Hua, WANG Zhenxing, ZHANG Xiaomeng, SHI Wei, XI Chengwei, WANG Conghui, WANG Liqun, ZHANG Bing. Mining and analysis of cardiac disorders risk signals based on adverse drug reaction monitoring data[J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 752-758.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240296

https://zgywjj.magtechjournal.com/EN/Y2024/V21/I7/752

References

[1] NMPA. National Medical Products Administration Announcement on the Publication of “Code for Quality Management of Pharmacovigilance”(No. 65 of2021)[EB/OL]. (2021-05-13)[2023-07-01]. https://www.nmpa.gov.cn/yaopin/ypggtg/20210513151827179.html.
[2] Hubei Food and Drug Administration. Prevention and treatment of pharmacogenic cardiovascular diseases(药源性心血管系统疾病的防治)[M]. Wuhan: Hubei People’s Press, 2012.
[3] Chinese Society of Clinical Oncology, Hematology Branch of Chinese Medical Association. Guidelines for the prevention and treatment of cardiactoxicity of anthracyclines (2020 version)(蒽环类药物心脏毒性防治指南2020版)[M]. Beijing: People’s Medical Publishing House, 2020.
[5] PATEL H, CALIP GS, DIDOMENICO RJ, et al.Comparison of cardiac events associated with azithromycin vs amoxicillin[J]. JAMA Netw Open, 2020, 3(9): e2016864.
[6] TIAN YH, XIA L, YANG C, et al.Mechanism and clinical prevention of sudden cardiac death caused byantipsychotics[J]. Anhui Journal of Preventive Medicine(安徽预防医学杂志), 2022, 28(5): 352-356.
[7] ALSHAYA OA, ALHAMED A, ALTHEWAIBI S, et al.Calcium channel blocker toxicity: a practical approach[J]. J Multidiscip Healthc, 2022, 8(15): 1851-1862.
[8] YAN MM, ZHENG H, WU SS, et al.Research on drug cardiactoxicity adverse reaction signal mining based on the database of Shanghai Clinical Pharmaceutical Quality Control Center[J]. Journal of Pharmacoepidemiology(药物流行病学杂志), 2022, 31(5): 309-313.
[9] YAN XY, WANG YC, ZHANG TY, et al.Application of signal detection methods for the occurrence time of adverse drug reactions in drug safety monitoring[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2017, 14(6): 350-352.
[10] Center for Drug Reevaluation, NMPA. Drug GVP Guidelines - Monitoring and Reporting(药品GVP指南-监测与报告)[M]. Beijing: China Medical Science Press, 2022: 70-102.
[11] TIEU C, BREDER CD.A critical evaluation of safety signal analysis using algorithmic standardized MedDRA queries[J]. Drug Saf, 2018, 41(12): 1375-1385.
[12] Center for Drug Reevaluation, NMPA. Drug GVP Guidelines - Risk Identification, Assessment, and Control (药品GVP指南-风险识、别评价与控制)[M]. Beijing: China Medical Science Press, 2022: 19-21.
[13] ANG PS, CHEN ZJ, CHAN CL, et al.Data mining spontaneous adverse drug event reports for safety signals in Singapore-a comparison of three different disproportionality measures[J]. Expert Opin Drug Saf, 2016, 15(5): 583-590.
[14] YUGO C, SHOKI A, YOSHITAKA Y.Analysis of adverse drug reaction risk in elderly patients using the Japanese Adverse Drug Event Report (JADER) database[J]. Biol Pharm Bull, 2017, 40(6): 824-829.
[15] MU YX, CAO YC, WANG YC.Research progress on the impact of gender differences on drug effects[J]. Journal of Jilin Medical College(吉林医药学院学报), 2017, 38(1): 69-71.
[16] SHI ZG, YIN H.Analysis of adverse drug reactions in 55 cases of Qingkailing injection[J]. Chinese Journal of Drug Application and Monitoring(中国药物应用与监测), 2009, 6(6): 361-363.
[17] WANG C, YE XF, QIAN W, et al.Association rules in drug adverse reaction signal detection[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2010, 7(3): 145-147.
[18] WANG J, YE XF, GUO XJ, et al.Exploration of statistical shrinkage parameters of disproportionality methods in spontaneous reporting system of China[J]. Pharmacoepidemiology and Drug Safety, 2015, 24: 962-970.
[19] MONTASTRUC G, FAVRELIERE S, SOMMET A, et al.Drugs and dilated cardiomyopathies: a case / noncase study in the French Pharmaco Vigilance Database[J]. Br J Clin Pharmacol, 2010, 69(3): 287-294.
[20] ZHANG B, LYU JT, ZHANG XM, et al.“Nature-Effect-Toxicity”: the foundation of clinical benefit-risk evaluation of traditional Chinese medicine[J]. Chinese Journal of Traditional Chinese Medicine and Pharmacy(中华中医药杂志), 2022, 37(1): 15-19.
[21] ZHANG B, SA RN, ZHANG XM, et al.Research progress on drug-induced cardiactoxicity[J].Chinese Journal of Pharmacovigilance(中国药物警戒), 2023, 20(8): 841-847.

[1]	LIN Lu, ZHAN Luchuan, LIU Xiaoqi, LIU Ju'e, WANG Laiyou, ZENG Ying, LAI Weihua. Establish triggers for active monitoring of digoxin adverse events based on the China hospital pharmacovigilance system [J]. Chinese Journal of Pharmacovigilance, 2024, 21(9): 1039-1043.
[2]	WU Fan, FU Linjie, ZHU He, XU Mengyan. Signal detection of adverse reaction of endothelin receptor antagonists based on FAERS and JADER database [J]. Chinese Journal of Pharmacovigilance, 2024, 21(9): 1056-1063.
[3]	LIU Ting, CAO Zhongqiang, HE Wenjia, YUAN Xiuli, CHEN Zebin, LI Xuejuan. One case of acute severe pancreatitis caused by pegaspargase and its etiology [J]. Chinese Journal of Pharmacovigilance, 2024, 21(9): 1075-1077.
[4]	SUN Yixin, NIE Xiaolu, WANG Xiaoling, GUO Peng. Comparative research on active post-marketing drug safety surveillance systems worldwide based on real-world data [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 892-899.
[5]	WEI Fenfang, WU Wenyu, LI Limin, TANG Biyu, WU Jianru. Foreign methods for benefit-risk assessment of pharmaceutical products [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 900-905.
[6]	WANG Yuxi, ZHANG Zonglin, WANG Yingli, CHEN Yafei, LI Junsheng, HUO Yanfei, XIE Yanjun, LIU Wenqi. 560 cases of adverse drug reaction/event caused by Mailu Shutong pills [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 921-924.
[7]	ZHAO Jun, DONG li, WANG Yang, LIANG Yu, YANG Xue, LI Enze. Adverse reaction/event reports of esmolol [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 925-930.
[8]	ZHANG Qian, YUN Yuan, HE Lian. Pharmaceutical care of hyperprolactinemia in a patient induced by risperidone [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 936-938.
[9]	CHAO Ying, ZHANG Xuemei, ZHANG Chengjian, WANG Bei. One case of ureterolith combined with gallstone caused by Ceftriaxone sodium for injection in children [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 943-945.
[10]	GUO Haiyan, HE Bo, YAN Hongli, YANG Xueting. One case of persistent hiccup caused by Wenxin Keli [J]. Chinese Journal of Pharmacovigilance, 2024, 21(8): 946-948.
[11]	WANG Dan, DONG Duo, TIAN Chunhua. Course of development of pharmocovigilance systems in China [J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 735-740.
[12]	SHAO Bo, GUO Xiaoxin. Review of pharmacovigilance of traditional Chinese medicine [J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 741-745.
[13]	LIU Yadi, ZHANG Xiaomeng, CAI Haili, CHEN Siying, WANG Yu, ZHANG Bing. Traditional Chinese medicine for prevention and treatment of adriamycin cardiotoxicity and an empirical study of evidence elements [J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 759-764.
[14]	CAI Haili, ZHANG Xiaomeng, LIU Yadi, LIU Shujia, GAO Fujun, WANG Yu, ZHANG Bing. Progress in construction and evaluation of a drug-induced cardiotoxicity model [J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 765-770.
[15]	CHENG Yijing, LI Tao, LIU Junting, HUANG Guimin, ZHONG Xuli, LIN Aihua, PAN Shoudong, LI Long, BAI Dongsheng, ZHAN Xiaojun, LIU Zhenjiang, REN Wei, NIE Xiaolu, TAI Jun. Safety evaluation of haemocoagulase agkistrodon for injection in children based on real world data [J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 787-790.