We read the recently published report by Saksena et al comparing cardiovascular outcomes of individual antiarrhythmic drugs versus rate-control drugs using propensity score–matched subcohorts in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial. The investigators reported increases in composite mortality and the frequency of cardiovascular hospital stay with individual antiarrhythmic drugs and noncardiovascular mortality and intensive care unit hospital stay with amiodarone compared to rate-control therapy.

We analyzed the outcomes of atrial fibrillation (AF) in the National Heart, Lung, and Blood Institute public-use, limited-access data set of the AFFIRM trial. We addressed the impact of lipid-lowering therapy (LLT) on outcomes of AF and observed decreases in all-cause mortality (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62 to 0.95, p = 0.01), ischemic stroke (HR 0.56, 95% CI 0.36 to 0.89, p = 0.01), cardiovascular mortality (HR 0.71, 95% CI 0.53 to 0.95, p = 0.02), and the combined end point (HR 0.81, 95% CI 0.69 to 0.96, p = 0.01) in patients with AF who were receiving LLT. Drug interactions and adverse effects have been reported with concomitant use of statins and amiodarone, especially rhabomyolysis. Multiple meta-analyses have revealed renin-angiotensin system–blocking agents to be beneficial in the prevention of new-onset and recurrent AF.

Although Saksena et al carried out an excellent propensity-matched cohort study considering 64 baseline patient characteristics deemed to affect antiarrhythmic drug selection, we believe that LLT and renin-angiotensin system–blocking drugs have effects on outcomes, which are not accounted for in their model.

Our studies were conducted using the National Heart, Lung, and Blood Institute limited-access data set and had inherent limitations of any retrospective analysis. We did not have information regarding the type and dosage of LLT used, inflammatory markers, or lipid profiles, and we did not study hospital stay as an outcome. Patients receiving LLT in our study were younger, had more cardiovascular co-morbidities, and were receiving aspirin, β blockers, and angiotensin-enzyme converting inhibitors. Thus, we cannot exclude the presence of residual confounding, but we believe that LLT and renin-angiotensin system blockade exert a significant impact on outcomes of AF. This effect certainly deserves attention, given that AFFIRM participants are similar to the general AF population.