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American Journal of Cardiovascular Drugs

18-12-2024 | Endocrine Therapy | Systematic Review

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database

Authors: Chengrong Zhang, Guoshuang Shen, Shengmei Li, Fei Ma, Huihui Li, Yuyao Tang, YongXin Li, Zhoujuan Li, Zijun Zhu, Tianlei Qiu, Zhilin Liu, Yi Zhao, Shifeng Huang, Fuxing Zhao, Fanzhen Kong, Jiuda Zhao

Published in: American Journal of Cardiovascular Drugs

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Abstract

Background

CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective

Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods

Eligible CVAEs were extracted from the ClinicalTrials.gov registry. A systematic search of electronic databases (PubMed, Embase, Cochrane Library, and important meetings) until 3 September 2023 was conducted. A disproportionality analysis was performed from the first quarter (Q1) of 2013 to Q1 of 2023 using data from the FAERS database. Study heterogeneity was assessed using the I2 statistic. Using Peto odds ratio (Peto OR) and inverse variance methods to calculate the risk and incidence of CVAEs associated with CDK4/6 inhibitors.

Results

In total, 17 RCTs with 23,437 patients were included in our meta-analysis. During the follow-up period of 8.4–34.0 months, CDK4/6 inhibitors significantly increased the risk of CVAEs (Peto OR, 1.86, 95% confidence interval, 1.30–2.68, P < 0.01). The rates of hypertension and QT prolongation were 68.07 (62.87–73.27) and 57.15 (50.83–63.48) per 1000 patients, respectively. Moreover, we identified nine CVAEs that were not reported in RCTs. These included acute coronary syndrome, arrhythmia, lymphoedema, hot flush, vein rupture, thrombophlebitis migrans, embolism venous, angiopathy and intracardiac thrombus, which were found to be strongly correlated with CDK4/6 inhibitors. Furthermore, the risk of CVAEs varied depending on the specific CDK4/6 inhibitors used, its combination with different endocrine therapies, and the patient's treatment stage.

Conclusion

CDK4/6 inhibitors increase the risk of CVAEs, some of which may lead to serious consequences. Early recognition and management of CVAEs is of great importance in clinical practice.

Registration

PROSPERO registration number CRD42023462059.
Appendix
Available only for authorised users
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Metadata
Title
Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database
Authors
Chengrong Zhang
Guoshuang Shen
Shengmei Li
Fei Ma
Huihui Li
Yuyao Tang
YongXin Li
Zhoujuan Li
Zijun Zhu
Tianlei Qiu
Zhilin Liu
Yi Zhao
Shifeng Huang
Fuxing Zhao
Fanzhen Kong
Jiuda Zhao
Publication date
18-12-2024
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-024-00709-6

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