High-dose atorvastatin fails to lower AF recurrence
MedWire News: Pretreatment with high-dose atorvastatin does not reduce atrial fibrillation (AF) recurrence after cardioversion, results of the "SToP AF" Trial indicate.
The study authors hypothesize that the inability of statin therapy to reduce AF recurrence may be explained by its failure to impact systemic oxidative stress.
SToP AF was a randomized, double-blind, placebo-controlled clinical trial conducted in 64 patients with AF or atrial flutter. They were randomly assigned to receive atorvastatin 80 mg or placebo, with treatment starting in the week before direct current cardioversion and continuing for 1 year afterwards.
The patients' mean age was 58 years, around four-fifths were male, and 85% were White. Baseline characteristics were comparable between the two treatment groups.
The study's primary endpoint was the time to first electrocardiographic documentation of recurrent AF after successful cardioversion. Kaplan-Meier survival curves showed no significant difference in this endpoint between the atorvastatin and placebo groups (29 vs 22 days, unadjusted hazard ratio [HR]=1.0).
The HR was essentially unchanged, at 0.99, after adjusting for potentially confounding demographic, clinical, and pharmacologic variables, report Samuel Dudley (University of Illinois at Chicago, USA) and fellow investigators writing in the Journal of Cardiovascular Electrophysiology.
Secondary analyses looking at underlying mechanisms found no difference in the burden of systemic oxidative stress (as indicated by the ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, and isoprostanes) at 1 month between the atorvastatin and placebo groups.
However, two of four inflammatory markers - interleukin-2 and high-sensitivity C-reactive protein - were significantly lower in the atorvastatin group at 1 month versus placebo.
Discussing their study, Dudley's team notes that inflammation, oxidative stress, and atrial fibrosis have been proposed as novel potential therapeutic targets for the upstream treatment and prevention of AF.
"In this study, we showed that, despite reducing some inflammatory markers and total cholesterol in the study group, high-dose atorvastatin did not affect the recurrence of AF after cardioversion."
They say their current evidence on the direction of causality between AF and inflammation remains "inconclusive," and conclude: "Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress."
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By Joanna Lyford