Pharmacological prevention in cardio-oncology: from bench-to-bedside

Abstract

Recent advancements in oncology have markedly enhanced cancer survival rates; however, anticancer therapies, particularly anthracyclines, pose significant cardiovascular (CV) risks, collectively referred to as cancer therapy-related cardiovascular toxicity (CTR-CVT). This review consolidates evidence on strategies to mitigate CTR-CVT especially associated with anthracyclines. Neurohormonal blockers, including ACE inhibitors, ARBs, and beta-blockers, constitute the foundation of prevention, although their efficacy varies: combinations such as ACEi/ARB with beta B yield mixed outcomes, whereas carvedilol offers antioxidant benefits beyond beta-blockade. Sacubitril/valsartan (ARNI) has demonstrated improvements in global longitudinal strain and LVEF preservation in the SARAH trial, albeit with associated hypotension risks. Aldosterone antagonists show potential, with spironolactone preserving LVEF and diastolic function, though eplerenone has not shown significant effects. Statins present conflicting data; the STOP-CA trial supports atorvastatin for LVEF preservation, while the PREVENT and SPARE-HF trials found no benefit. Emerging evidence suggests sodium-glucose cotransporter-2 inhibitors (SGLT2i), such as dapagliflozin and empagliflozin, as promising agents, with preclinical and early clinical data indicating cardioprotection through metabolic modulation, anti-inflammatory effects, and reduced oxidative stress. Gaps remain in understanding CTR-CVT pathophysiology, risk stratification, and the translation of preclinical findings. Future efforts should prioritize personalized approaches, dynamic risk assessment (e.g., HFA-ICOS tool), and a paradigm shift from oxidative stress to cardiometabolic dysfunction. Multidisciplinary collaboration is essential to optimize oncological outcomes while minimizing CV toxicity, with SGLT2i representing a key frontier for validation in ongoing trials.