Abstract 15020: A Placebo-Controlled, Double-Blind, Randomized, Multicenter Study to Assess the Effects of Dronedarone on Atrial Fibrillation Burden in Subjects with Permanent Pacemakers (HESTIA)
Introduction: Dronedarone (Dro) is a benzofuran anti-arrhythmic drug (AAD) approved in non-permanent atrial fibrillation (AF) pts. In clinical trials, Dro reduced the risk of AF recurrence by approximately 30% in non-permanent AF pts. The effect of Dro on AF burden (AFB, total time in AF) has not been previously assessed and was the goal of HESTIA.
Methods: HESTIA (NCT01135017) was conducted in pts with clinically indicated dual-chamber pacemakers (PM) capable of recording and storing electrograms. PM programming was adjusted to optimize AF detection. Pts with AFB >1% were randomized 1:1 to Dro 400 mg BID or placebo (Pla) and followed for 12 weeks. PMs were interrogated after a 4 week baseline period and at 4 and 12 weeks of treatment. The primary efficacy measure was the change in AFB from baseline over the 12 week treatment period. AFB changes were evaluated for Dro and Pla groups separately, and by direct comparison between groups. Permanent AF, severe or recently decompensated HF, and use of AADs were exclusions. PM settings and AFB evaluations were adjudicated by a core lab blinded to treatment assignment. The study was terminated early due to slow recruitment without breaking the blind.
Results: Two hundred eighty-five pts were screened; 112 pts were randomized. Pts were age 76+9 years, 60% male, 84% hypertensive, 65% sick sinus syndrome, 26% diabetes, and 15% HF. At baseline, 82% received rate lowering medications and 73% oral anticoagulants. Baseline mean (geometric) AFB was 8.77% for Pla and 10.14% for Dro. After 12 weeks of treatment, mean AFB increased by 12.8% (P=0.450) in P pts and decreased by 54.4% (P=0.0009) in Dro pts. Compared to Pla, Dro reduced AFB by 59% over the 12 week duration of the study (P=0.0015) and by 63% at 4 weeks of treatment. (P=0.0009). HR during AF was reduced approximately 4 beats/min with Dro (P=0.285). There were no deaths, strokes, or major bleeding events during the study. Adverse events (AEs) were higher in the Dro group (56% vs 65%) as were discontinuations due to AEs (5.5% vs 14%).
Conclusion: Dronedarone 400 mg BID reduced PM AFB by 59% over a 12 week observation period. This effect was observed as early as 4 weeks. The safety was consistent with prior reports in non-permanent AF patients
- © 2012 by American Heart Association, Inc.