Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.
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引用次数: 0
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.
期刊介绍：
Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents.
Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations.
The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
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