Abstract 4357286: Atorvastatin and Pulse Wave Velocity in Anthracycline-based Chemotherapy

Background: Increased aortic stiffness is associated with cardiovascular morbidity and mortality, and is an adverse effect of anthracyclines. To date, there is no evidence-supported intervention that preserves vascular function among anthracycline recipients. While statins have been shown to preserve vascular function in patients not treated with anthracyclines, their effectiveness in patients treated with anthracyclines remains unclear. Hypothesis: We hypothesized that atorvastatin would protect against the anthracycline-induced deterioration of vascular function, assessed by aortic pulse wave velocity (PWV). Methods: We conducted a post-hoc analysis of cardiac MRI-derived PWV data from participants with newly diagnosed lymphoma in the STOP-CA trial, who were scheduled to undergo anthracycline-based chemotherapy and randomized to atorvastatin or placebo for 12 months. In patients with available data, PWV was measured at baseline and 12 months. The primary endpoint was a ≥1 standard deviation (SD) increase in PWV. The secondary endpoint was a ≥0.15 m/s increase, a previously identified mean annual rise in patients with increased cardiovascular risk. Incident heart failure (HF) events were evaluated at 24 months. Results: Paired PWV data were available in 152 participants (mean age 51±16 years, 47% female, 82 with atorvastatin). Age (median 56 for atorvastatin vs. 52 years for placebo, p=0.11) and baseline PWV were higher in the atorvastatin group (6.5±1.9 vs. 5.7±1.8 m/s, p=0.016). At 12 months, PWV was similar between the groups (6.5±2.0 vs. 6.8±2.0 m/s, p=0.47). The mean interval change in PWV was significantly lower in the atorvastatin group (0.1±0.5 vs. 1.0±0.9 m/s, p<0.001). A ≥1SD increase (0.8 m/s) was observed in 5% of the atorvastatin and 50% of the placebo groups (odds ratio [OR] 0.05, 95% confidence interval [CI] 0.02-0.16, p<0.001). A ≥0.15 m/s increase in PWV was noted in 37% of the atorvastatin and 89% of the placebo group (OR 0.08, 95% CI 0.03-0.19, p<0.001). A ≥1 SD increase in PWV was associated with a mean LVEF decline of 2.7% (95% CI -4.65 to -0.81, p=0.006). All participants (n=8) who developed incident HF by 24 months had a ≥0.15 m/s increase in PWV (p=0.023). Conclusion: In lymphoma patients undergoing anthracycline-based chemotherapy, atorvastatin demonstrated vasculoprotective effects by reducing the odds of a significant increase in aortic stiffness over 12 months. An increase in PWV may be associated with a higher risk for subsequent HF events.