Research Progress on Cardiovascular Adverse Events Associated with CDK4/6 Inhibitor Therapy

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have significantly improved survival outcomes in patients with HR+/HER2- advanced or metastatic breast cancer; however, the associated cardiovascular adverse events (CVAEs) are receiving increasing attention. This review systematically examines the clinical application of CDK4/6 inhibitors, as well as the epidemiological characteristics, potential mechanisms, and risk factor assessment of related CVAEs. Based on key clinical trials, meta-analyses, and real-world evidence, the three currently marketed CDK4/6 inhibitors—palbociclib, ribociclib, and abeciriblin—exhibit differences in their profiles of CVAEs, with QT interval prolongation associated with ribociclib and thromboembolic events associated with abeciriblin and palbociclib being particularly prominent. The underlying mechanisms involve multiple pathways, including off-target toxicity resulting from the inhibition of CDK4/6 expression in cardiac myocytes and vascular endothelial cells, leading to cell cycle arrest, endothelial dysfunction, and a prothrombotic state; simultaneously, these agents may contribute to vascular injury and arrhythmias through immune modulation and inflammatory activation; Furthermore, hERG potassium channel blockade and drug-induced electrolyte disturbances may exacerbate the risk of QT prolongation and malignant arrhythmias. Future research should further elucidate the molecular mechanisms of CVAEs, explore predictive biomarkers, and focus on the cardiovascular safety of combination therapies and next-generation CDK4/6 inhibitors. This will ensure cardiovascular safety while enhancing anticancer efficacy, thereby advancing the clinical practice of "integrated cancer-heart care."