14th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 2000

Jan. 29 - Feb. 5, 2000
Marilleva, Trento, Italy

RT-179

Effects of 200 mg sustained release diltiazem on ventricular rate control in chronic atrial fibrillation (D-D-CAF Study)

Marcello Chimienti, Vincenzo Santinelli*, Maurizio Moizi**, Gianluca Botto***, Serena Barbieri.
Polyclinic of Monza, Monza, and Department of Internal Medicine, University of Pavia, Pavia, *Department of Cardiology, University “Federico II”, Naples, **Division of Cardiology, Sondrio Hospital, Sondrio, ***Division of Cardiology, S. Anna Hospital, Como, Italy

Introduction

The control of ventricular response in chronic atrial fibrillation (AF) has traditionally been attempted with digoxin; the drug is relatively effective for this purpose at rest, but ventricular rate is rarely well controlled on exercise or with high catecholamine levels¹. Beta-blockers, in contrast, do limit heart rate (HR) at peak exercise, but this has generally not been reflected in an improvement in exercise tolerance². In addition, because of their well-known negative inotropic activity and other important side effects (bronchospasm, peripheral vasoconstriction, hyperglycemia), beta-blockers cannot be utilized in patients with underlying ventricular impairment, as well as in other clinical situations. Calcium channel blockers, particularly diltiazem and verapamil, are frequently utilized as first-line drugs in controlling ventricular rate, thanks to their negative dromotropic activity at the AV node level. Both drugs increase refractory period and decrease conduction velocity of the AV node³. Their electrophysiologic effects are experimentally demonstrated to be rate-dependent, i.e. more evident at higher stimulation rates; this is clinically revealed by their strong slowing effect in high rate AF or during physical activity, despite a relatively small effect on AV nodal conduction during sinus rhythm⁴. These drugs are generally well tolerated and have only few contraindications.

Many clinical studies have widely demonstrated oral diltiazem to be very effective in controlling ventricular rate during chronic AF^5-11. In most of these studies the drug was utilized in the standard formulation, which usually requires 3 to 4 daily doses to maintain a 24-hour efficacy, owing to the rapid catabolism and short half-life of this drug¹². Recently, a new sustained release formulation has been commercially available, which assures a constant activity with a once-daily administration. Only sporadically the once-daily 300 mg formulation has been used to control ventricular rate during chronic AF¹¹, while no data are still available on the effects of the 200 mg formulation in this indication.

The aim of this study was to compare efficacy and safety of sustained-release diltiazem at a dose of 200 mg once daily (D200) with standard diltiazem at a dose of 60 mg three times a day (D60), given to control ventricular rate in patients with chronic AF (Diltiazem versus Diltiazem in Chronic Atrial Fibrillation: D-D-CAF Study).