Anthracyclines, which are key to many chemotherapeutic protocols, have been associated
with increased vascular stiffness, a major factor associated with cardiovascular morbidity
and mortality. There is no evidence-based intervention to prevent anthracycline-associated
vascular dysfunction.To investigate whether atorvastatin pretreatment is associated
with attenuation of the anthracycline-induced increase in aortic stiffness.This study
is a secondary analysis of a double-blind, randomized clinical trial (Statins to Prevent
the Cardiotoxicity From Anthracyclines [STOP-CA]). Enrollment occurred between January
25, 2017, and September 10, 2021, with the last follow-up on October 10, 2022. Primary
analyses were reported on August 8, 2023. STOP-CA was a multicenter trial across 9
academic centers in the US and Canada. Participants were patients with newly diagnosed
lymphoma scheduled to undergo anthracycline-based chemotherapy with no clinical indication
for a statin.Atorvastatin (40 mg, once daily) or placebo for 12 months.This subanalysis
of the STOP-CA trial includes post hoc end points with cardiac magnetic resonance
imaging-derived aortic arch pulse wave velocity (PWV) and aortic distensibility (AD).
An intention-to-treat approach was applied. The proportions of participants with a
1 SD or more increase in PWV and a 1 SD or more decrease in ascending aortic distensibility
(AAD) were calculated in each group over 12 months. An increase in PWV of 0.15 m per
second or more, a previously defined annual rate in individuals of similar age, was
also assessed as a secondary end point.Of the 300 participants (150 randomized to
atorvastatin and 150 randomized to placebo), 152 (mean [SD] age, 51 [17] years; 72
female [47%]; 82 treated with atorvastatin) had paired PWV data, and 168 had paired
AD data. The PWV values remained similar in the atorvastatin group (mean [SD], 6.5
[1.9] vs 6.5 [2.0] m per second) but increased in the placebo group (5.7 [1.8] vs
6.8 [2.0] m per second) over 12 months. A 1 SD or more increase (0.8 m per second)
in PWV was observed among 4 of 82 patients (5%) with atorvastatin and 35 of 70 patients
(50%) with placebo (odds ratio, 0.05; 95% CI, 0.02 to 0.16; P < .001) at 12 months.
A 1 SD or more decrease (1.8 × 10-3 mm Hg-1) in AAD was observed among 6 of 88 patients
(7%) with atorvastatin and in 14 of 80 patients (18%) with placebo. A 1 SD or more
increase in PWV was associated with a mean left ventricular ejection fraction decline
of 2.70% (95% CI, -4.65% to -0.81%; P = .006).Pretreatment with atorvastatin was associated
with preservation of vascular function among patients with lymphoma undergoing anthracycline-based
chemotherapy.ClinicalTrials.gov Identifier: NCT02943590.
