Digoxin and Platelet Activation in Patients With Atrial Fibrillation: In Vivo and In Vitro Study

Background Digoxin use was shown to be associated with an increased risk of cardiovascular events in atrial fibrillation (AF). We hypothesized that digoxin may affect cardiovascular risk by increasing platelet activation. Methods and Results Post hoc analysis of a prospective study of anticoagulated patients with AF. Patients were divided into 2 groups balanced for age, sex, and cardiovascular risk factors: digoxin users (n=132) and nonusers (n=388). Urinary excretion of 11‐dehydro‐thromboxane B2 (TxB2), a marker of platelet activation, and serum digoxin concentration (SDC) were measured. In vitro experiments were performed on platelets from healthy subjects and AF patients, which were incubated with scalar doses of digoxin (0.6–2.4 ng/mL) with or without prestimulation with a sub‐threshold of collagen. Median 11‐dehydro‐TxB2 was 105.0 (interquartile range, 60.0–190.0) ng/mg creatinine, and median SDC was 0.65 (interquartile range, 0.40–1.00) ng/mL. Urinary 11‐dehydro‐TxB2 and SDC were correlated (rs=0.35...