Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial

Area of Science:

• Cardiology
• Oncology
• Pharmacology

Background:

• Anthracyclines are vital chemotherapy agents but can cause cardiotoxicity.
• Statins are explored for cardioprotective effects against chemotherapy-induced heart damage.
• The PREVENT trial investigated atorvastatin's efficacy in preventing anthracycline cardiotoxicity.

Purpose of the Study:

• To evaluate atorvastatin's effect on oxidative and nitrosative stress biomarkers in patients receiving anthracyclines.
• To determine if these biomarkers mediate the lack of atorvastatin's effect on left ventricular ejection fraction (LVEF).

Main Methods:

• The PREVENT trial randomized breast cancer/lymphoma patients to atorvastatin or placebo.
• Cardiac MRI and 13 biomarkers (nitric oxide metabolites, PON-1, myeloperoxidase) were assessed.
• Principal component analysis and mediation analysis explored biomarker changes and their relation to LVEF.

Main Results:

• Atorvastatin significantly reduced paraoxonase-1 (PON-1) activity (Cluster 2; P=0.024).
• Modest, non-significant reductions were observed in arginine methylation metabolites (Cluster 1; P=0.081).
• Biomarker clusters did not mediate the effect of atorvastatin on LVEF.

Conclusions:

• Atorvastatin had minimal impact on oxidative/nitrosative stress biomarkers in this low-risk population.
• These findings offer mechanistic insights into why atorvastatin did not improve LVEF in the PREVENT trial.
• Statins may not prevent anthracycline cardiotoxicity through modulation of these specific stress biomarkers.