Challenges in the implementation of cardio-oncology trials: lessons learnt from investigating statins in the prevention of anthracycline cardiotoxicity

Despite advanced in targeted cancer therapies, anthracyclines remain essential in treating various malignancies, albeit with risks of cancer therapy-related cardiac dysfunction (CTRCD). Out of the myriad of mitigation strategies for CTRCD, statins are an attractive preventive therapy for anthracycline associated CTRCD given their widespread availability, cheap costs and added benefit of atherosclerotic cardiovascular disease (ASCVD) risk reduction. Recent trials of PREVENT, SPARE-HF, and STOP-CA investigated atorvastatin's efficacy in preventing CTRCD, with mixed outcomes. While STOP-CA showed a significant reduction in CTRCD rates (22% vs. 8% in placebo), PREVENT and SPARE-HF found no statistical differences between statin and placebo groups. The trials faced challenges such as selection bias, exclusion of patients with comorbidities, and reliance on imaging-derived outcomes, which may not reflect clinically meaningful benefits. This calls for improved trial designs that prioritize diverse patient recruitment, longer follow-ups, and clinically relevant endpoints to enhance the translational impact of findings. Addressing these challenges collaboratively between oncology and cardiology will be crucial for optimizing patient outcomes in this vulnerable population. Future studies should emphasize both immediate cardioprotective effects and long-term cardiovascular benefits of statins, especially in the context of atherosclerotic cardiovascular disease in cancer survivors.