Dronedarone matches up to Asians with AF, atrial flutter

Asians with atrial fibrillation (AF) or atrial flutter (AFL) do well with dronedarone, which lowers the risk of hospitalization for cardiovascular (CV) events or death from any cause to a similar extent as in non-Asian patients from the ATHENA trial, according to the results of a post hoc analysis.

Compared with placebo, dronedarone yielded a significant protection against the risk of the primary composite outcome of CV hospitalization or all-cause death in both Asian (hazard ratio [HR], 0.541, 95 percent confidence interval [CI], 0.320–0.914) and non-Asian (HR, 0.768, 95 percent CI, 0.696–0.848) populations. [Clin Ther 2022;doi:10.1016/j.clinthera.2022.07.005]

The antiarrhythmic drug also prolonged the median time to the first AF/AFL event recurrence in Asians (183 vs 92 days; p=0.165) and non-Asians (534 vs 196 days; p<0.001).

Why time to the first AF/AFL event recurrence was considerably shorter in the Asian population, despite these patients having lower incidences of cardiovascular diseases than their non-Asian counterparts, may be explained by the inclusion of more persistent forms of AF/AFL in the Asian population. In addition, it could be due to late diagnosis of AF that may be caused by hesitation or inability of the patient to seek or access medical care or under and missed diagnosis by the healthcare professional, the investigators explained. [Future Cardiol 2009;5:547-556]

“On the other hand, Asian patients could be more alert to symptomatic palpitation due to recurrent AF/AFL, thus seeking available care earlier and avoiding hospitalizations,” they added.

In terms of safety, the investigators noted a higher percentage of patients from the Asian population who developed reported treatment-emergent adverse events (TEAEs) and serious adverse events than patients from the non-Asian population, while being comparable between the dronedarone- and placebo-treated patients.

“This finding may be explained by the pharmacogenetic differences and environmental and cultural factors associated with Asian or other racial/ethnic backgrounds that can set forth adverse reactions to cardiovascular drugs and predictable alterations in drug metabolism,” they pointed out. [Clin Trans Sci 2020;13:861-870; BMJ 2006;332:1177-1181]

Taken together, “the reduction in incidence of AF/AFL event recurrences and the delayed median time to the first AF/AFL event recurrence associated with dronedarone in the Asian population in the current analysis are reassuring and in line with the results seen in the EURIDIS/ADONIS trials relative to placebo and in other Asian studies in relation to other antiarrhythmic drugs,” the investigators said. [N Engl J Med 2007;357:987-999; Clin Ther 2014;36:1169-1175]

Patients with AF should receive a holistic and integrated approach to improve symptom management with either rate or rhythm control, according to the investigators. This is on top of stroke prevention with anticoagulation therapy and card and comorbidity risk management.

Therefore, as supported by a subanalysis from the ATHENA trial in patients with known AF/AFL onset and data from EAST-AFNET4, which included patients with AF and HF with preserved ejection fraction and asymptomatic patients, early rhythm control using dronedarone should be considered in Asian patients with AF, they said. [Clin Cardiol 2020;43:1469-1477; Eur J Heart Fail 2022;24:1094-1101; Circulation 2021;144:845-858; Eur Heart J 2022;43:1219-1230]