Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction.
Carvedilol is a beta- and alpha-adrenergic-blocking drug with clinically important antiarrhythmic properties. It possesses anti-ischemic and antioxidant activity and inhibits a number of cationic channels in the cardiomyocyte, including the HERG-associated potassium channel, the L-type calcium channel, and the rapid-depolarizing sodium channel. The electrophysiologic properties of carvedilol include moderate prolongation of action potential duration and effective refractory period; slowing of atrioventricular conduction; and reducing the dispersion of refractoriness. Experimentally, carvedilol reduces complex and repetitive ventricular ectopy induced by ischemia and reperfusion. In patients, carvedilol is effective in controlling the ventricular rate response in atrial fibrillation (AF), with and without digitalis, and is useful in maintaining sinus rhythm after cardioversion, with and without amiodarone. In patients with AF and heart failure (HF), carvedilol reduces mortality risk and improves left ventricular (LV) function. Large-scale clinical trials have demonstrated that combined carvedilol and angiotensin-converting enzyme inhibitor therapy significantly reduces sudden cardiac death, mortality, and ventricular arrhythmia in patients with LV dysfunction (LVD) due to chronic HF or following myocardial infarction (MI). Despite intensive neurohormonal blockade, mortality rates remain relatively high in patients with post-MI and nonischemic LVD. Recent trials of implantable cardioverter-defibrillators added to pharmacologic therapy, especially beta blockers, have shown a further reduction in arrhythmic deaths in these patients.
Naccarelli
Gerald V
GV
Division of Cardiology, Cardiovascular Center, Penn State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. gnaccarelli@psu.edu
Lukas
Mary Ann
MA
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D011412:Propanolamines / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D000317:Adrenergic alpha-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol