Related Experiment Video
Updated: May 10, 2026
23:33
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Dronedarone in high-risk permanent atrial fibrillation
Stuart J Connolly1, A John Camm, Jonathan L Halperin
1Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada. connostu@phri.ca
The New England Journal of Medicine
|November 16, 2011
Summary
Dronedarone increased major vascular events, including stroke and heart failure, in high-risk permanent atrial fibrillation patients. This study found the drug unsafe for this population, leading to early termination.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Dronedarone is used for intermittent atrial fibrillation, reducing hospitalizations and mortality.
- The drug exhibits antiadrenergic effects and can lower heart rate and blood pressure.
- Its potential antiarrhythmic effects on the ventricle were noted.
Purpose of the Study:
- To investigate if dronedarone reduces major vascular events in high-risk permanent atrial fibrillation patients.
- To evaluate the safety and efficacy of dronedarone in this specific patient group.
Main Methods:
- A randomized, placebo-controlled trial involving 3236 patients aged 65+ with permanent atrial fibrillation and vascular risk factors.
- Patients received either dronedarone or a placebo.
- Coprimary outcomes included major vascular events (stroke, myocardial infarction, embolism, cardiovascular death) and cardiovascular hospitalizations or death.
Main Results:
- The study was halted early due to safety concerns after enrolling 3236 patients.
- Dronedarone significantly increased the risk of the first coprimary outcome (HR 2.29, P=0.002), cardiovascular deaths (HR 2.11, P=0.046), and stroke (HR 2.32, P=0.02).
- Increased hospitalizations for heart failure (HR 1.81, P=0.02) and deaths from arrhythmia were observed in the dronedarone group.
Conclusions:
- Dronedarone is associated with increased rates of heart failure, stroke, and cardiovascular death in high-risk permanent atrial fibrillation patients.
- The drug should not be used in this patient population.
- The PALLAS trial (NCT01151137) provides critical safety data regarding dronedarone use.
Related Concept Videos
01:22Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
01:24Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers
Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...
01:12Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of the heart's...
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
01:29Disturbances in Heart Rhythm
Arrhythmia or dysrhythmia refers to an abnormal heart rhythm caused by a defect in the heart's conduction system. It can cause the heart to beat irregularly, too quickly, or too slowly, leading to symptoms like chest pain, shortness of breath, and fainting. Factors such as stress, caffeine, alcohol, nicotine, cocaine, certain drugs, congenital defects, diseases, and electrolyte abnormalities can trigger arrhythmias.
Arrhythmias are categorized by their speed, rhythm, and origin. A slow heart...
Arrhythmias are categorized by their speed, rhythm, and origin. A slow heart...
01:25Dysrhythmias VI: Management of Dysrhythmias
Dysrhythmia management involves a multifaceted approach, incorporating pharmacological treatments, medical procedures, surgical interventions, lifestyle modifications, and patient education.Pharmacological ManagementAntiarrhythmic Drugs:Class I (Sodium Channel Blockers): This class includes quinidine and procainamide, which reduce the speed of impulse conduction in the heart, stabilize the cardiac membrane, and control arrhythmias. Quinidine and procainamide are Class IA agents that prolong the...