Best Rate-Control Drugs in Atrial Fib Identified

VANCOUVER, B.C. — Over time, the most effective approach to pharmacologic rate control in patients with atrial fibrillation is a β-blocker in combination with digoxin, Brian Olshansky, M.D., reported at a meeting sponsored by the International Academy of Cardiology.

He presented a secondary analysis of data from the landmark Atrial Fibrillation Followup Investigation of Rhythm Management (AFFIRM) study, a National Heart, Lung, and Blood Institute-sponsored prospective, randomized trial that was the largest ever to compare rate control versus rhythm control as treatment for atrial fibrillation (AF). The retrospective secondary analysis involved the 2,027 AFFIRM participants randomized to ventricular rate control, with an average follow-up of 3.5 years. Selection of the rate-control drugs was left to the discretion of the patient's physician. The secondary analysis aimed to answer two key questions: Is pharmacologic rate control achievable over the long haul? And what drugs are most effective—β-blockers, calcium channel blockers, digoxin, or combinations?

The answer to the first question was a clear yes. Adequate rate control, both at rest and during exercise, was achieved in 58% of patients with the first drug or combination of drugs on which they were placed. At 1 year, adequate rate control, as stringently defined by the AFFIRM investigators, was achieved in 64% of patients. And the success rate continued to climb over time. At 2 years, overall rate control, both while resting and exercising, was achieved by more than 70% of patients. By 5 years the rate approached 80%.

But these success rates required considerable medication changes. Indeed, 37% of patients had a change in rate-control medication over the course of 5 years. Although the initial success rates with β-blocker and calcium channel-blocker monotherapy were similar, over time more patients on a calcium channel blocker or digoxin were changed over to a β-blocker than vice versa. In the first year alone, 23% of patients switched from calcium channel blockers to β-blockers, while 19% switched from β-blockers to calcium channel blockers, noted Dr. Olshansky, chief of electrophysiology at the University of Iowa, Iowa City.

Seven percent of patients, unable to achieve adequate rate control despite multiple attempts, then underwent atrioventricular junctional ablation with insertion of a permanent pacemaker to control ventricular rate.

The definition of rate control used by the AFFIRM investigators was much more rigorous than typical in clinical practice. Adequate rate control in AFFIRM required an average heart rate at rest of 80 bpm or less, plus either a maximum heart rate of no more than 110 bpm during a 6-minute walk or an average heart rate of 100 bpm or less during 24-hour ambulatory Holter monitoring.

One of the big surprises in the secondary analysis was how well patients did on digoxin as a single rate-control drug. Indeed, rate control with digoxin alone during exercise was similar to that with a β-blocker. “We've all been taught that digoxin has little effect on atrial fibrillation, but it did appear that rate control occurred in the group taking digoxin,” the cardiologist said.

Audience member Win-Kuang Shen, M.D., said the repeated office visits and medication adjustments many AF patients require to achieve rate control constitutes a considerable societal burden. Perhaps earlier resort to an ablate-and-pace strategy makes more sense from the cost-effectiveness and quality-of-life standpoints, proposed Dr. Shen, professor of medicine at the Mayo Clinic, Rochester, Minn.

Dr. Olshansky replied that he believes rate control with drugs to be a reasonable strategy, but at some point mutually agreed upon by patient and physician, it's time to say “enough,” rather than continue to try various permutations of medications.