Best rate control drugs for permanent AF

OSLO, NORWAY. Permanent (long-standing persistent) atrial fibrillation (AF) is defined as AF that cannot be terminated by electrical cardioversion, or by the use of pharmaceutical drugs. Thus it makes no sense to prescribe antiarrhythmics to permanent afibbers since the only effects they will have are adverse. This also applies to digoxin (Lanoxin). Rate control drugs, specifically beta-blockers and calcium channel blockers can, however, be useful in bringing down the heart rate and thus making the patient more comfortable.

A group of Norwegian physicians now report on a study they did to determine the most effective rate control drug. They evaluated four common rate control drugs in a group of 60 permanent afibbers (70% male) with an average age of 71 years. To be included, the participants had to have a resting heart rate in excess of 80 bpm and a minimum heart rate during the day of 100 bpm. Patients with heart failure, ischemic heart disease (angina), renal failure or liver failure were excluded. The patients were randomized to receive one of the following drugs for 3 weeks:

  • Metoprolol (Toprol) slow-release tablets – 100 mg/day
  • Diltiazem (Cardizem) sustained-release capsules – 360 mg/day
  • Verapamil (Isoptin SR) modified release tablets – 240 mg/day
  • Carvedilol immediate-release tablets – 25 mg/day

Following a 2-week washout period, they were assigned another one of the four drugs, and so on, until each patient had tried all four drugs. Before starting the trial and on the last day of the four treatment periods, the heart rate at rest and the average 24-hour heart rate were measured (with ECG and Holter monitoring respectively) and the patients completed questionnaires regarding arrhythmia-related symptoms. The questionnaire rated frequency (from 0 to 4) and severity (from 1 to 3) of 16 symptoms potentially associated with AF, thereby generating frequency and severity scores ranging from 0 to 64 and 0 to 48, with higher scores representing worse symptoms. Results of the trial were as follows:

-
Resting*
24-Hour*
Night-time*
Frequency**
Severity**
Baseline
95
96
79
13.4
8.1
Diltiazem
77
75
66
10.5
6.0
Verapamil
82
81
76
11.3
7.3
Metoprolol
81
82
72
12.0
7.4
Carvedilol
78
84
76
12.6
8.1

* Heart Rate (average)
** Symptom

It is clear from this data that the sustained-release diltiazem is the optimum rate control drug for permanent afibbers. It is of interest to note that the time spent with a heart rate above 110 bpm was also reduced very significantly with diltiazem (from 266 minutes at baseline to 32 minutes with diltiazem). Also noteworthy is the finding that women tended to report a significantly greater frequency and severity of symptoms, both at baseline and after treatment. The Norwegian researchers conclude that diltiazem is the most effective drug for reducing heart rate in patients with permanent AF. It also significantly reduces arrhythmia-related symptoms whereas beta-blockers do not.
Ulimoen, SR, et al. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. American Journal of Cardiology, October 27, 2012 [Epub ahead of print]

Editor’s comment: It is interesting that the Norwegian research team included the following statement in the article: “The present study was initiated by the investigators and performed without the cooperation or financial support from the drug companies.” This is indeed a rare occasion these days!