Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter.
Level 3 - non-randomized controlled study
Retrospective cohort study
PubMed 26063741 · doi:10.1161/CIRCEP.114.002339
What was done
A retrospective cohort chart review of 1,404 patients initiated on oral dofetilide for atrial fibrillation suppression at the Cleveland Clinic between 2008 and 2012. The study evaluated the incidence and predictors of in-hospital adverse events—particularly Torsade de pointes (TdP)—during drug loading, as well as 1-year all-cause mortality associated with continued versus discontinued use.
What was found
During drug loading, 17 patients (1.2%) developed TdP (10 had cardiac arrest requiring resuscitation with 1 death, 5 had syncope/presyncope, and 2 were asymptomatic). Dofetilide loading was discontinued in 105 patients (7.5%) due to excessive QTc prolongation or TdP. Factors correlated with TdP were female sex, a 500-μg dose, reduced ejection fraction, and magnitude of QTc increase from baseline. One-year all-cause mortality was higher in patients who continued dofetilide compared with those who discontinued it (hazard ratio 2.48; 95% CI, 1.08–5.71; P=0.03) and in patients who experienced loading-phase TdP compared with those who did not (17.6% vs 3.0%; P<0.001).
Why it matters
The findings reinforce the necessity of FDA-mandated inpatient telemetry monitoring during dofetilide initiation and identify clinical risk factors for proarrhythmia, while raising caution regarding long-term mortality in patients maintained on the drug.
Limits
Single-center retrospective design subject to potential confounding by indication (underlying clinical differences between patients maintained on dofetilide versus those discontinued). Cause-specific mortality and post-discharge adherence or monitoring data were not detailed in the abstract.
Cited by
- supports Tikosyn (dofetilide) carries an approximate 1-in-100 risk of inducing torsades de pointes.