A new study published in PLOS One noted that dofetilide and sotalol are potent QT interval–prolonging agents that are often used in patients with HFpEF, for which atrial fibrillation is a common comorbidity.
Purdue University College of Pharmacy–led researchers and colleagues tested their hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol was increased in patients with HFpEF.
To determine that, investigators conducted a retrospective cohort study using electronic health records from the Indiana Network for Patient Care (January 31, 2010–May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, the study team identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no heart failure (HF; n = 729).
For purposes of the study, QT prolongation was defined as heart rate–corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy.
The results indicated that QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7%, and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the researchers found that adjusted odds of QTc prolongation were significantly higher in patients with HFpEF (odds ratio [OR] = 1.98; 95% CI, 1.17-3.33) and in those with HFrEF (OR = 5.23; 3.15-8.67) compared with those with no evidence of HF.
“The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF,” the authors noted.
Background information in the article advised that torsades de pointes (TdP) is a life-threatening ventricular arrhythmia that can be caused by more than 200 drugs on global markets, including commonly used antiarrhythmic drugs, antibiotics, antidepressants, antipsychotic agents, and others. QT interval prolongation on the ECG suggested an increased risk of TdP, the authors wrote.
HFrEF is a risk factor for drug-induced TdP, with the incidence of dofetilide-induced TdP at 3.3%, compared with less than 1% in those without HF. At the same time, the incidence of TdP associated with ibutilide is 1.7% to 4.1% in patients without HF but is higher in those with HFrEF.
“HFrEF is a risk factor for sotalol-induced TdP,” according to the researchers. “We have shown previously that patients with HFrEF demonstrate increased sensitivity to drug-induced QT interval lengthening. Consequently, guidelines recommend avoidance of QT interval-prolonging drugs such as ibutilide in some populations with HFrEF, due to the enhanced risk of TdP.”
The research into adverse drug effects in HFpEF is important, the study noted, because at least 50% of patients with HF have that type and its prevalence continues to increase.
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