Comparison of the efficacy and acceptability of nicardipine and propranolol, alone and in combination, in mild to moderate hypertension.

1. We evaluated the relative efficacies and tolerability of various low-dose combinations of nicardipine and propranolol in patients with mild-moderate essential hypertension (DBP Phase V of greater than 90-125 mmHg; WHO Grades I and II) in order to select the best one. 2. Sixty patients completed the double-blind, balanced, randomised three-way cross-over protocol, with each phase lasting 4 weeks, and in which twice daily nicardipine 40 mg or propranolol 80 mg was compared with four twice daily combinations of nicardipine (20 or 30 mg) plus propranolol (40 or 80 mg). 3. At 'peak' effect time (i.e., 2 h post-dosing) all four treatment combinations were significantly more effective than propranolol, with effects ranging from 9-23 mmHg (systolic) and 5-15 mmHg (diastolic). Only the two 30 mg nicardipine combinations with propranolol were more effective than nicardipine monotherapy, further reducing BP by 8-13 mmHg (systolic) and 5-7 mmHg (diastolic); there were no significant differences between them. 4. 'Trough' diastolic pressures were not different between treatments and 'trough' BP control was sub-optimal on all treatments. 5. 70% of patients on nicardipine monotherapy, 33% of those on propranolol monotherapy and 30% of patients during the placebo run-in complained of symptoms. In terms of complaint rates, there was little to choose between the four combinations (27-33%). Serum potassium and creatinine levels were elevated following propranolol monotherapy by 0.19 mmol 1-1 and 6.5 mumol 1-1 respectively (P less than 0.01 for both) and following the nicardipine 30 mg/propranolol 80 mg combination. Nicardipine monotherapy elevated serum T4 levels by an average of 0.57 ng dl-1 (P less than 0.05). 6. The twice daily combination of nicardipine 30 mg plus propranolol 40 mg was therefore the optimum one in terms of its efficacy and tolerability. Further studies need to be performed to test the hypothesis that a higher dose of propranolol might ameliorate troublesome vasodilator side effects. However, none of the treatments studied was ideal for clinical use in the twice daily dosage used in this study.