Dronedarone may improve outcomes in patients with AF, HF
Dronedarone for atrial fibrillation may lower risk for all-cause death and CV hospitalization regardless of HF status or left ventricular ejection fraction, according to research published in the European Journal of Heart Failure.
“Despite this substantial clinical overlap and the recognition of AF as a potential therapeutic target in HF with preserved EF, limited evidence-based strategies are available for its management,” Muthiah Vaduganathan, MD, MPH, cardiologist at Brigham and Women’s Hospital and instructor in medicine at Harvard Medical School, and colleagues wrote. “Designed as a non-iodinated congener of amiodarone with less tissue accumulation, dronedarone has been previously shown to increase mortality among hospitalized decompensated patients with HF and severe LV dysfunction. Whether its use in patients with HFpEF and AF in more stable settings can improve outcomes remains unknown.”
The ATHENA trial
The researchers conducted a post hoc analysis of the ATHENA randomized controlled trial that evaluated the efficacy of dronedarone (Multaq, Sanofi) for the prevention of CV hospitalization or death in patients with paroxysmal or persistent AF/atrial flutter.
As Healio previously reported, dronedarone reduced the incidence of CV hospitalizations or death in patients with AF/atrial flutter by 24% and reduced time to first hospitalization by 25.5%.
Based on real-world data, the 2020 European Society of Cardiology AF guideline designated dronedarone as a class IA recommendation for long-term rhythm control in patients with AF and HFpEF, according to the study.
For the post hoc analysis of ATHENA, researchers evaluated the effects of dronedarone in patients with paroxysmal or persistent AF/atrial flutter with HF across the spectrum of LVEF and without HF.
Overall, 12% of the cohort had HFpEF or HF with mildly reduced EF (HFmrEF; defined as LVEF > 40%; evidence of structural heart disease; and NYHA class II/III or diuretic use), 9% had HF with reduced EF or LV dysfunction (LVEF 40%) and 79% did not have HF.
The primary outcome was a composite of all-cause mortality and CV hospitalization.
Among patients with HFpEF and HFmrEF (mean LVEF, 57%), the mean age was 73 years and 37% were women.
Dronedarone for AF/atrial flutter in HF
During a mean follow-up of 21 months, researchers reported that dronedarone was associated with lower risk for the primary composite outcome compared with placebo (HR = 0.76; 95% CI, 0.69-0.84) regardless of HF status (P for interaction > .1).
In participants with HFpEF and HFmrEF, dronedarone use was associated with lower risk for the primary composite endpoint compared with placebo (HR = 0.79; 95% CI, 0.61-1.03).
Moreover, the lower risk for the primary endpoints was consistent across the range of LVEF in HF without heterogeneity (P for interaction = .71).
The researchers observed that the rates of mortality, CV hospitalization and HF hospitalization favored dronedarone compared with placebo in those with HFpEF and HFmrEF but were not statistically significant.
In addition, dronedarone was associated with greater occurrence of permanent drug discontinuation due to treatment-emergent adverse events (7% vs. 4%), which mainly consisted of nausea or diarrhea.
“Dronedarone, when compared with placebo, was consistently associated with lower rates of death or cardiovascular hospitalization in patients with AF/atrial flutter, including among patients with HFpEF and HFmrEF,” the researchers wrote. “Among patients with HF, clinical benefits of dronedarone were apparent across a spectrum of LVEF and extended to LVEF 60%. Dronedarone appeared safe in this HFpEF and HFmrEF subgroup without excess in mortality or HF hospitalizations. Taken together, these data support the safety and efficacy of dronedarone in paroxysmal or persistent AF/atrial flutter and HF with higher LVEF.”
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