Rate Control of Rapid Atrial Fibrillation

Abstract & Commentary

Source: Wattanasuwan N, et al. Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone. Chest 2001;119:502-506.

The mainstays of treating atrial fibrillation (AF) include ventricular rate control, conversion to and maintenance of sinus rhythm, and prevention of embolic events. The primary goal of emergency department (ED) management is rate control, as it is the main determinant of the patient’s symptoms. Digoxin, which produces a rapid ventricular response, was the first-line treatment for AF for many years until the early 1990s, when it was supplanted by calcium-channel blockers and beta-adrenergic blockers. The calcium-channel blocker diltiazem currently is among the most popular choices for acute rate control.

This prospective, randomized, open-label study from Long Island College Hospital examined the efficacy of combination diltiazem and digoxin vs. diltiazem alone (all given intravenously) for acute ventricular rate control in patients presenting with AF and rapid ventricular rates. Fifty-two patients met the inclusion criteria, defined as a ventricular rate of greater than 100 bpm. Patients with systolic blood pressure less than 90 mmHg, acute congestive heart failure (CHF), acute coronary syndromes, ventricular rate greater than 200 bpm, coexisting unstable medical conditions, pre-excitation syndrome, history of allergy to the study drugs, and those who had taken any antiarrhythmic medications within one week prior to presentation were excluded.

Both groups received diltiazem 0.25 mg/kg intravenously (IV) over two minutes followed by a maintenance continuous infusion of 10 mg/hr. At 15 minutes, a second bolus of 0.35 mg/kg of IV diltiazem was given if the ventricular rate remained greater than 100 bpm. Patients in the combination group also received 1 mg of intravenous digoxin, given as 0.5 mg initially, followed by two doses of 0.25 mg at two and four hours. Doses of digoxin were withheld if the ventricular rate was less than 55 bpm at the scheduled dose time. Patients achieving successful rate control were switched from intravenous diltiazem to 60 mg given orally every six hours, with the first dose given 30 minutes prior to stopping the infusion. All patients had heart rate and cardiac rhythm monitored continuously in the cardiac care unit (CCU) for 12 hours, and had an echocardiogram within 24 hours of ventricular rate control.

Successful rate control was defined as a rate of less than 100 bpm persisting for one hour or conversion to sinus rhythm. Loss of rate control in patients who had achieved a successful rate control was defined as increased rate to greater than 100 bpm persisting for longer than than 30 minutes or conversion from sinus rhythm back to AF. Study end points included the number of patients with successful rate control, time to successful rate control, and number of episodes of loss of rate control.

The study groups were not significantly different in age, gender, the presence of certain co-morbidities, chronicity of AF, initial heart rate, initial blood pressure, left atrial size, ejection fraction, or the presence of left ventricular (LV) hypertrophy. All patients achieved successful ventricular rate control at 12 hours. The time to ventricular rate control was shorter in the combination group (15 ± 16 min vs 22 ± 22 min), but this was not statistically significant. The number of episodes of loss of rate control was significantly fewer in the combination group, with six patients experiencing 14 episodes of loss of rate control vs. 11 patients with 39 episodes in the diltiazem-alone group. Twelve patients in the combination group and 14 in the diltiazem-alone group converted to sinus rhythm, most of whom remained in sinus rhythm throughout the study period. Seven patients in the combination group and 11 in the diltiazem-alone group required the second bolus of diltiazem. Blood pressures remained comparable between groups throughout the study.

Comment by Jacob W. Ufberg, MD

Previous studies have shown that digoxin used alone for acute ventricular rate control in AF results in a delayed rate control effect and probably lower success rates. Diltiazem results in rapid and effective rate control, but is associated with frequent loss of rate control that necessitates repeated dosages. These additional dosages of a negative inotrope may be undesirable in patients with poor left ventricular systolic function. Previous studies have shown that oral diltiazem in combination with oral digoxin controls rate more effectively than oral diltiazem alone, both at rest and during exertion.

This study demonstrates that diltiazem and digoxin used in combination intravenously result in similar times to rate control, but significantly fewer episodes of loss of rate control when compared with diltiazem alone. The patients in the combination group required fewer repeat boluses of diltiazem, an effect that is desirable for patients with poor LV function. It has been reported previously that episodes of loss of rate control may be associated with a longer median length of hospitalization. Although the authors did not study length of stay, it is conceivable that combination therapy may lead to a decrease in length of stay (CCU and/or hospital) when compared to diltiazem alone. In summary, intravenous combination therapy with diltiazem and digoxin for rate control of rapid AF appears to offer an advantage over diltiazem alone in patients meeting the criteria set forth by the authors.