A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers

Purpose Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13–19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden. Methods Pacemakers were adjusted to optimize AF detection. Patients with AF burden \u3e1 % were randomized to dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week treatment period. Patients with permanent AF, severe/recently decompensated heart failure, and current use of antiarrhythmic drugs were excluded. AF burden was assessed by a core laboratory blinded to treatment assignment. Results From 285 patients screened, 112 were randomized (mean age 76 years, 60 % male, 84 % hypertensive, 65 % with sick sinus syndrome, 26 % with diabetes mellitus type II, 15 % with heart failure). Baseline mean (SEM) AF burden was 8.77 % (0.16) for placebo and 10.14 % (0.17) for dronedarone. Over the 12-week study period, AF burden compared to baseline decreased by 54.4 % (0.22) (P = 0.0009) with dronedarone and trended higher by 12.8 % (0.16) (P = 0.450) with placebo. The absolute change in burden was decreased by 5.5 % in the dronedarone group and increased by 1.1 % in the placebo group. Heart rate during AF was reduced to approximately 4 beats/min with dronedarone (P = 0.285). Adverse events were higher with dronedarone compared to placebo (65 vs 56 %). Conclusions Dronedarone reduced pacemaker-assessed the relative AF burden compared to baseline and placebo by over 50 % during the 12-week observation period

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction

BACKGROUND Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P CONCLUSIONS In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing

Quality of Life and Clinical Outcomes in Elderly Patients Treated with Ventricular Pacing as Compared with Dual-Chamber Pacing

ABSTRACT Background Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes. Methods The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dualchamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey. Results The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death). However, 53 patients assigned to ventricular pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not those with atrioventricular block, had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing. Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction, but not in those with atrioventricular block. Conclusions The implantation of a permanent pacemaker improves health-related quality of life. The quality-of-life benefits associated with dualchamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction. (N Engl J Med 1998;338:1097-104.