Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation.

We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation. Medium-dose diltiazem was comparable to therapeutic dose of digoxin at rest (88 +/- 19 vs 86 +/- 12 beats/min) but superior during peak exercise (154 +/- 23 vs 170 +/- 20 beats/min; p less than .05). High-dose diltiazem resulted in better control of heart rate than digoxin both at rest (79 +/- 17 beats/min; p less than .05) and exercise (136 +/- 25 beats/min; p less than .05) but was associated with side effects in 75% of the patients. Combined therapy of digoxin and diltiazem enhanced the effect of digoxin alone and resulted in significantly better control of heart rate at rest (67 +/- beats/min with medium-dose and 65 +/- beats/min with high-dose diltiazem) and during peak exercise (132 +/- 32 and 121 +/- 24 beats/min, respectively). However, the difference in heart rate between these two doses was not significant. Reduction of heart rate combined with concomitant effect on blood pressure resulted in a significant fall in pressure-rate product at rest from 10,077 +/- 1708 mm Hg/min on digoxin alone to 7877 +/- 1818 mm Hg/min after the addition of medium-dose diltiazem (p less than .05) and during exercise form 25,670 +/- 3606 to 18,439 +/- 4115 mm Hg/min (p less than .05). Continued therapy with digoxin combined with diltiazem 240 mg/day for 21 +/- 8 days in nine patients showed persistent effect on heart rate and blood pressure without any toxic manifestations or change in serum digoxin (1.5 +/- 0.4 vs 1.3 +/- 0.4 ng/ml) or plasma diltiazem concentrations (204 +/- 72 vs 232 +/- 129 ng/ml). In conclusion, medium-dose diltiazem when combined with digoxin is an effective and safe regimen for the treatment of patients with chronic atrial fibrillation and enhances digoxin-mediated control of heart rate both at rest and during exercise.