Digoxin use is associated with increased platelet and endothelial cell activation in patients with nonvalvular atrial fibrillation.
OBJECTIVE
The purpose of this study was to determine whether digoxin use is associated with increased flow cytometric markers of endothelial cell and platelet activation in patients with nonvalvular atrial fibrillation (AF).


BACKGROUND
Increased intracellular calcium is a key event in platelet activation, and several studies have demonstrated that digitalis activates platelets in vitro. Intracellular calcium also is a key regulator of endothelial cell function, and endogenous digitalis-like substances have been shown to affect biologic processes in endothelial cells.


METHODS
We studied 30 patients with nonvalvular AF. We measured the levels of (1) platelet expression of P-selectin (CD62P), (2) platelet microparticles (PMP); and (3) endothelial microparticles (EMP) identified by anti-CD31 (EMP31) and by anti-E-selectin antibodies (EMP62E).


RESULTS
Patients who were taking digoxin (n = 16; mean digoxin level = 0.93 ng/dL) did not demonstrate any significant differences in clinical or echocardiographic characteristics compared with patients not taking digoxin (n = 14). Patients taking digoxin had significantly increased levels of CD62P expression in platelets and platelet-leukocyte conjugates and markedly increased markers of endothelial activation: EMP62E and EMP31. After adjusting for potential confounders (including age, congestive heart failure, coronary artery disease, ejection fraction, antiplatelet, beta-blocker, and calcium channel blocker use), the differences persisted.


CONCLUSIONS
Digoxin use in patients with AF is associated with increased levels of endothelial and platelet activation. If digitalis activates endothelial cells and platelets at pharmacologic doses, use of digitalis in conditions such as AF could predispose to thrombosis and vascular events.
Chirinos
Julio A
JA
Department of Medicine, Division of Cardiology, University of Miami School of Medicine, Miami, Florida 33136, USA.
Castrellon
Aurelio
A
Zambrano
Juan Pablo
JP
Jimenez
Joaquin J
JJ
Jy
Wenche
W
Horstman
Lawrence L
LL
Willens
Howard J
HJ
Castellanos
Agustin
A
Myerburg
Robert J
RJ
Ahn
Yeon S
YS
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D003430:Cross-Sectional Studies; D004077:Digoxin / Q000494:pharmacology* / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D019007:P-Selectin / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D019007:P-Selectin; D004077:Digoxin