Portal de Periódicos da CAPES

Digoxin use is associated with increased risk of stroke in patients with non-valvular atrial fibrillation — a nationwide population-based cohort study

2013; Elsevier BV; Volume: 169; Issue: 2 Linguagem: Inglês

10.1016/j.ijcard.2013.08.103

1874-1754

Shih‐Sheng Chang, Kuan‐Cheng Chang, Yu-Chen Wang, Chih-Hsin Muo, Pei‐Ying Pai, Chi-Bin Chang, Chi‐Yuan Li, Fung-Chang Sung,

Cardiac electrophysiology and arrhythmias

Atrial fibrillation (AF) is associated with increased risk of morbidity and mortality. Digoxin is often used as a rate control agent in AF patients, particularly in those with systolic heart failure. Although digoxin use in AF patients can reduce heart failure symptoms, increase exercise capacity and decrease hospitalizations [ [1] The Digitalis Investigation Group The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997; 336: 525-533 Crossref PubMed Scopus (2674) Google Scholar ], unfavorable effects on long-term outcomes have been reported [ 2 Corley S.D. Epstein A.E. DiMarco J.P. et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Circulation. 2004; 109: 1509-1513 Crossref PubMed Scopus (1017) Google Scholar , 3 Hallberg P. Lindback J. Lindahl B. Stenestrand U. Melhus H. RIKS-HIA groupDigoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol. 2007; 63: 959-971 Crossref PubMed Scopus (93) Google Scholar ]. In the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, a post-hoc analysis showed a higher rate of mortality in patients treated with digitalis medication [ [2] Corley S.D. Epstein A.E. DiMarco J.P. et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Circulation. 2004; 109: 1509-1513 Crossref PubMed Scopus (1017) Google Scholar ]. A study of the “Registry of Information and Knowledge about Swedish Heart Intensive care Admissions” (RIKS-HIA) demonstrated that AF patients without heart failure had a higher mortality rate if they were treated with digoxin [ [3] Hallberg P. Lindback J. Lindahl B. Stenestrand U. Melhus H. RIKS-HIA groupDigoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol. 2007; 63: 959-971 Crossref PubMed Scopus (93) Google Scholar ]. The use of digoxin in non-valvular AF patients has been associated with increased platelet and endothelial cell activation [ [4] Chirinos J.A. Castrellon A. Zambrano J.P. et al. Digoxin use is associated with increased platelet and endothelial cell activation in patients with nonvalvular atrial fibrillation. Heart Rhythm. 2005; 2: 525-529 Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar ], and the digitalis-mediated platelet activation has been attributed to its intensification of the intracellular calcium concentrations [ [5] Schoner W. Scheiner-Bobis G. Endogenous and exogenous cardiac glycosides and their mechanisms of action. Am J Cardiovasc Drugs. 2007; 7: 173-189 Crossref PubMed Scopus (162) Google Scholar ]. Thus, it is conceivable that the effects of endothelial and platelet activation as a consequence of digoxin treatment may enhance the risk of stroke in AF patients, which can be further linked to higher mortality rates observed in previous studies [ 2 Corley S.D. Epstein A.E. DiMarco J.P. et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Circulation. 2004; 109: 1509-1513 Crossref PubMed Scopus (1017) Google Scholar , 3 Hallberg P. Lindback J. Lindahl B. Stenestrand U. Melhus H. RIKS-HIA groupDigoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol. 2007; 63: 959-971 Crossref PubMed Scopus (93) Google Scholar ]. Therefore, we sought to investigate the risk of stroke among AF patients with and without digoxin use in an Asian cohort of 982,232 patients covered by the universal health insurance program in Taiwan.