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Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study
Author(s) -
Charnigo Richard,
Khairy Paul,
Guo Jing,
Shohoudi Azadeh,
Elayi Claude S.
Publication year - 2018
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/pace.13350
Subject(s) - medicine , digoxin , atrial fibrillation , hazard ratio , heart failure , cardiology , confidence interval , ejection fraction , cohort , proportional hazards model , cohort study , randomization , randomized controlled trial
Background Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow‐up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data. Methods MSM is a newer statistical approach, which estimates causal association in the absence of randomization. MSM more effectively accounts for time‐varying treatment and mitigates potential biases, in contrast to the two statistical approaches used in prior analyses of the AFFIRM data. Results Among 4,060 patients in AFFIRM, 660 (16.3%) died during follow‐up. Digoxin was associated with significantly higher mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11–1.60, P = 0.002) and in 3,121 patients without HF (HR 1.36, 95% CI 1.07–1.72, P = 0.011). There was a trend toward higher mortality with digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96–1.72, P = 0.090). Associations were nonsignificant in 463 patients with HF and left ventricular ejection fraction (EF) ≥40% and in 155 patients with EF ≤30%. Conclusions Digoxin is associated with significantly increased mortality among AFFIRM patients collectively, as determined by MSM statistical methodology. However, the impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.