Summary
Background CDK4/6 inhibitors is highly valued, but the incidence of cardiovascular events (CVAEs) associated with CDK4/6 inhibitors is not clear.
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 FDA Adverse Event Reporting System database. Study heterogeneitywas assessed using the I2 statistic. Using Peto OR and inverse variance methods to calculate the risk and incidence of CVAEs associated with CDK4/6 inhibitors.
Findings 21 RCTs and cohort trials (n=24,331) were included. During the follow-up period of 8.4 to 34.0 months, CDK4/6 inhibitors significantly increased the risk of CVAEs (Peto OR, 1.64, 95% confidence interval, 1.23 - 2.21, P < 0.01). The rates of QT prolongation and deep vein thrombosis were 98.83 (89.6-100.1) and 6.41 (5.23-7.18) per 1000 patients, respectively. Moreover, we identified 11 CVAEs that were not reported in RCTs or cohort studies, acute coronary syndrome, atrial fibrillation, and mobile thrombophlebitis etc. were 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.
Interpretation 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.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This study was supported by two funding sources: 1. The National Natural Science Foundation of China (Grant Number: 82160859), and 2. The Kunlun Talents Program of Qinghai Province for high-end innovative and entrepreneurial talents. The funders had no role in the study design, nor in the collection, analysis, interpretation of data, writing of the report, or the decision to submit the article for publication.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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Footnotes
↵1 First author
Guoshuang Shen:M.D., guoshuangshen{at}126.com
Shengmei Li,M.D., 861447701{at}qq.com
Fei Ma,M.D., drmafei{at}126.com
Huihui Li:M.D., huihuili82{at}163.com
Yuyao Tang: B.D., tangyuyao1999{at}163.com
YongXin Li: B.D., lyx000706{at}163.com
Zhoujuan Li: B.D., liyixin131488{at}163.com
Zijun Zhu: B.D., 826110835{at}qq.com
Tianlei Qiu B.D., 1179150989{at}qq.com
Zhilin Liu: M.D., lzl_doctor{at}163.com
Yi Zhao.M.D., zywm0001{at}163.com
Fuxing Zhao: M.D., 18797349621{at}163.com
Shifeng Huang: M.D., hsflzdx{at}163.com
Fanzhen Kong: U.D., 18009718886{at}163.com
Jiuda Zhao: M.D., jiudazhao{at}126.com
Data Availability
YES