Overall 46 studies (n=1,062 patients) were included: 36 RCTs (n=867); one cross-over non-randomised trial (n=52); one case-control (n=23), and eight observational time series studies (n=120). Quality of included studies varied from fair to good.
β-blockers alone (10 studies): One study reported improved heart rate control at rest compared with digoxin. Four studies reported that exercise heart rate was better controlled compared with digoxin. Two studies found that β-blockers (sotalol and xamoterol) improved exercise tolerance compared with no treatment (one study) and digoxin (one study); six studies reported no improvement in exercise capacity. β-blockers were associated with significant dose-related side-effects.
Combination of β-blockers with digoxin (17 studies): Combination therapy compared with digoxin resulted in better control of resting (13 studies) and exercise heart rates (19 studies). The effect of the combination therapy on exercise tolerance was mixed: five studies reported deterioration in exercise capacity; three studies reported some improvement; and 10 reported no change.
Calcium antagonists alone (10 studies): Monotherapy with diltiazem compared to digoxin resulted in improved exercise heart rate control, but not exercise capacity (five studies). Monotherapy with verapamil compared to digoxin resulted in improved exercise heart rate (three studies) and exercise capacity (two studies). No effect on exercise tolerance was found in two studies.
Combination of diltiazem with digoxin (11 studies): Combination therapy compared to digoxin resulted in improved resting and exercise heart rates in 11 studies. Exercise tolerance was found to improve in only two out of eight studies.
Combination of verapamil with digoxin (12 studies): Combination therapy compared with digoxin alone resulted in improved resting and exercise heart rates (nine studies) and ambulatory heart rate (four studies). The effect on exercise tolerance was mixed: improvement was reported in three studies and no change was found in four studies.
Diltiazem and verapamil were associated with significant dose-related side-effects.