Problem AF
Format Double-blinded multi-center RCT
Treatment Dronedarone 400mg BD
Control Placebo
Population 4628 patients
Inclusion criteria Paroxysmal or persistent AF, meet at least one of the following requirements:

Age of at least 70 years
Arterial hypertension (with ongoing therapy involving at least two antihypertensive drugs of different classes)
Diabetes mellitus
Previous stroke, transient ischemic attack, or systemic embolism
Left atrial diameter greater than or equal to 50 mm, as measured on M-mode echocardiography
Left ventricular ejection fraction less than or equal to 40%.

For each patient, a 12-lead electrocardiogram (ECG) showing atrial fibrillation or flutter and obtained within 6 months before randomization had to be available. A second 12-lead ECG within the same period had to show sinus rhythm.

During the course of the trial, overall mortality figures were lower than expected. Therefore, the steering committee elected to change the inclusion criteria to enrich the risk profile of the overall study population. On the basis of the revised criteria, patients 75 years of age or older were eligible, whether or not they had any previously specified risk factors, but patients 70 years of age or older were eligible only if they had one or more of the other risk factors. Patients younger than 70 years of age were no longer eligible. This protocol amendment was implemented on March 8, 2006.
Exclusion criteria Patients were ineligible for participation in the trial if they had any of the following cardiac conditions:

Permanent atrial fibrillation
Aan unstable hemodynamic condition (i.e., decompensated heart failure within the previous 4 weeks)
New York Heart Association (NYHA) class IV congestive heart failure
Planned major surgery
Acute myocarditis
Bradycardia with a heart rate of less than 50 beats per minute or a PR interval of more than 0.28 second
Previous clinically significant sinus-node disease, if the patient was not currently being treated with a pacemaker

General (noncardiac) exclusion criteria were as follows:

Any severe noncardiac illness limiting life expectancy
Pregnancy, breast-feeding, or lack of adequate birth control among women of childbearing potential
A calculated glomerular filtration rate at baseline of less than 10 ml per minute
A potassium level of less than 3.5 mmol per liter, if not currently being corrected
A requirement for concomitant medication that was prohibited (i.e., other class I or III antiarrhythmic drugs).
Follow-up Mean 21+-5 months
Primary endpoint First hospitalization due to cardiovascular events or death
Secondary endpoint(s) Death from any cause, death from cardiovascular causes, and hospitalization due to cardiovascular events
Details .
Brief summary: Dronedarone reduced death/CV admissions in elderly low-risk paroxysmal/persistant AF patients
PAPER: Effect of dronedarone on cardiovascular events in atrial fibrillation.
Date 12 Feb 2009
Journal N Engl J Med. 2009 Feb 12;360(7):668-78.
Information Dronedarone vs. placebo for paroxysmal/persistent (NOT permanent) AF
-24% RRR CV hospitalizations or death
-30% RRR CV deaths
-45% reductions in deaths from arrhythmia
-17% (not significant) reduction in all-cause mortality
-No excess in CCF admissions

N.B. Patients all aged >75 or >70 with CV risk factors