Best Single Drug for Rate Control of Atrial Fibrillation

Abstract & Commentary

By Michael H. Crawford, MD, Editor

Source: Ulimoen SR, et al. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Am J Cardiol 2013;111:225-230.

Beta-blockers are widely considered first-line therapy for heart rate control in patients with permanent atrial fibrillation (AF), but few comparative effectiveness data with other drugs are available. Thus, this group of investigators from Norway conducted a randomized prospective, crossover, single-blinded (investigator) study of four different drugs in 80 AF patients. Exclusion criteria included the presence of ischemic heart disease, systolic heart failure, and AF other than permanent. After 80 patients were randomized, 20 patients were excluded for medical contraindications (4), adverse effects (12), or other events (4), including a cerebral bleed and a stroke. The frequency of adverse events was similar in the four drug groups: diltiazem (3), verapamil (1), metoprolol (5), and carvedilol (3). Treatment with each drug was for 3 weeks to allow for washout of the previous drug. On the last day of each drug treatment, resting and 24-hour average heart rate were obtained. The results were 24-hour heart rate was lowest on diltiazem (P < 0.001); baseline 96 beats per minute (bpm), diltiazem 75 bpm, verapamil 81 bpm, metoprolol 82 bpm, and carvedilol 84 bpm. However, all drugs reduced heart rate compared to baseline (P < 0.001 for all). Symptom frequency and severity were significantly reduced by diltiazem, but verapamil only reduced symptom frequency and the two beta-blockers reduced neither. The authors concluded that in patients with permanent AF who needed heart rate control, diltiazem was more effective than verapamil, metoprolol, and carvedilol for reducing heart rate symptoms.


This study is interesting because very few comparative efficacy studies of marketed drugs are done and rate control in permanent AF is a common clinical problem. The biggest issue with such studies is selecting comparable doses of the drugs tested. Diltiazem was given at the maximum recommended U.S. dose (360 mg/day). The verapamil dose was half of the maximal recommended dose (240 mg/day), which may have explained its poorer performance relative to diltiazem. Also, a relatively short-acting form of verapamil was used. The metoprolol dose (100 mg/day) and the carvedilol dose (25 mg/day) were midrange. Thus, dosing considerations alone would seem to favor diltiazem.

It is noteworthy that all four drugs given once daily were effective in significantly reducing 24-hour mean heart rate compared to the baseline. At the doses used, calcium antagonists did better at controlling heart rate and symptoms. The strengths of the study included the relatively large size, random crossover design, and the inclusion of women (one-third of the final study population). Also, the study was not funded by the pharmaceutical industry. Although the study had flaws, I believe it highlights the efficacy of the nondihydropyridine calcium antagonists for controlling heart rate in patients with permanent AF.