The departure from recommending digoxin as the first-line treatment in patients with chronic atrial fibrillation (AF) by current UK guidelines is premature, according to investigators in a British Medical Journal review.
The UK National Institute for Clinical Excellence last year published guidelines that replaced digoxin with beta blockers or calcium antagonists as the recommended initial monotherapy for the control of heart rate in patients with chronic AF.
“Digoxin has been the mainstay of treatment for many years, so new recommendations relegating digoxin should be evidence based and safe,” write Theodora Nikolaidou and Kevin Channer, from the Royal Hallamshire Hospital in Sheffield.
But the reviewers found little evidence to support replacing digoxin with either of the other treatments as monotherapy.
Instead, they found that improvements in both heart rate variability and exercise tolerance were shown only with the combination of digoxin and a beta blocker or calcium channel blocker. Indeed, they found some evidence that beta blockers used alone may worsen exercise capacity.
Nikolaidou and Channer reviewed a total of 57 studies, including 25 randomised double-blind controlled trials, assessing digoxin, beta blockers, calcium antagonists and combinations for rate control in chronic AF.
They found that beta-blocker monotherapy was better than digoxin alone at controlling heart rate at rest in just one out of 10 studies, although it improved rate control during exercise in four of the studies. Nevertheless, in six other studies, beta blocker use alone did not improve exercise capacity.
Several studies showed that the combination of beta blocker and digoxin gave greater improvements in heart rate control at rest and during exercise compared with digoxin alone. The combination’s effect on exercise capacity was inconsistent, causing deterioration in some studies, but improvement or no change in others.
The calcium channel blocker diltiazem was found in five studies to be better than digoxin at controlling heart rate during exercise, but not during rest, and it failed to improve exercise capacity. However, most of the 11 studies assessing the combination of diltiazem and digoxin showed that it provided better heart rate control at rest and during exercise than digoxin alone, and two studies showed the combination gave improved exercise tolerance.
Similar results were seen with the calcium antagonist verapamil as monotherapy in comparison with digoxin, although exercise tolerance improved with verapamil in two of three studies that assessed this outcome.
Again, the combination of verapamil with digoxin improved rate control at rest and during exercise compared with digoxin alone, but, despite this, exercise tolerance was not improved consistently.
Nikolaidou and Channer noted that use of both verapamil and diltiazem was limited by their negative inotropic effects and “considerable” dose-related side effects.
They concluded: “We believe that the combination of digoxin and a beta blocker or calcium antagonist should be recommended as first-line management. We would emphasise that it is safest to start treatment with digoxin first.”