Dronedarone holds promise for preventing atrial fibrillation, flutter recurrence
In the treatment of atrial fibrillation (AF) or flutter (AFL), the class III antiarrhythmic drug (AAD) dronedarone is safe and effectively delays recurrence in patients regardless of whether they have undergone cardioversion or not, according to a posthoc analysis presented at the European Society of Cardiology (ESC) Congress 2019.
“Dronedarone may be an effective treatment option for preventing AF/AFL recurrence,” said lead study author Prof Harry Crijns from the Maastricht University Medical Center in the Netherlands.
In the current analysis, Crijns and his team assessed the baseline characteristics and treatment outcomes of 1,237 adult patients who participated in the phase III ADONIS* and EURIDIS** trials. All patients had ≥1 episode of AF/AFL in the preceding 3 months and in sinus rhythm for ≥1 hour before randomization to treatment with either dronedarone 400 mg twice daily or placebo for 12 months.
The patients were grouped based on their cardioversion requirement: 364 patients required the procedure within 5 days prior to randomization (mean age, 63.8 years; 72.5 percent male; dronedarone, n=243; placebo, n=121), while 873 did not (mean age, 62.7 years; 68.0 percent male; dronedarone, n=585; placebo, n=288). Those who underwent cardioversion notably had a lower mean heart rate and greater degree of structural heart disease, congestive heart failure and left atrial enlargement.
Nevertheless, the median time to first adjudicated recurrence was longer with dronedarone vs placebo both in cardioversion (50 vs 15 days; hazard ratio [HR], 0.76, 95 percent CI, 0.59–0.97; p=0.02) and no-cardioversion subgroups (150 vs 77 days; HR, 0.76, 0.64–0.90; p<0.01), as was median time to first symptomatic recurrence (cardioversion: 347 vs 87 days; HR, 0.65, 0.49–0.87; no cardioversion: 288 vs 120 days; HR, 0.74, 0.62–0.90; p-both<0.01). [ESC 2019, abstract P1903]
Crijns noted that first recurrences were generally symptomatic and that adjudicated recurrences occurred earlier in the cardioversion vs no-cardioversion subgroup. Furthermore, dronedarone was associated with fewer first AF hospitalizations within 12 months compared with placebo (cardioversion: 7.8 percent vs 12.4 percent; HR, 0.60, 0.31–1.18; no-cardioversion: 8.4 percent vs 10.4 percent; HR, 0.74, 0.47–1.17).
The most common symptoms associated with AF/AFL recurrence in both patient subgroups were palpitations and fatigue, with the majority of events being mild-to-moderate in severity. Generally, the frequency and severity patterns of symptoms were similar in the treatment arms.
Safety of dronedarone was similar to placebo and consistent with the overall observations from EURIDIS/ADONIS regardless of cardioversion status and differences in comorbidities. For example, in the subgroup of patients who underwent cardioversion, the rates were 64 percent vs 66 percent for treatment-emergent adverse events (TEAEs), 19 percent vs 26 percent for serious TEAEs, 9 percent vs 6 percent for treatment discontinuations, and 0 percent vs 1 percent for deaths.
“Our observations with dronedarone may not reflect findings with other AADs,” Crijns said. “Large prospective studies are warranted to conclusively determine the benefits and risks of AAD treatment following cardioversion.”
*American-Australian-African trial with dronedarone in patients with atrial fibrillation or atrial flutter for the maintenance of sinus rhythm
**European trial in atrial fibrillation or flutter patients receiving dronedarone for the maintenance of sinus rhythm