Alpha-blockade and calcium antagonism: an effective and well-tolerated combination for the treatment of resistant hypertension

Objective: To test whether the combination of calcium antagonism is additive with the other newer antihypertensives, namely [alpha]-blockers and angiotensin converting enzyme (ACE) inhibitors. Design: Three-way double-blind, Latin-square crossover studies in two groups of 12 patients with essential hypertension. The three treatment periods were amlodipine, doxazosin (study A) or enalapril (study B), and the combination of amlodipine with the second drug. Methods: Each treatment was taken for 1 month, preceded by a 2-week single-blind run-in period, in which the patients received a low dose of doxazosin (study A) or enalapril (study B) to enable recruitment of patients with moderate or severe hypertension. Blood pressure, foot volume and plasma noradrenaline concentration were measured at the end of each run-in and treatment period. Results: The combination of [alpha]-blockade and calcium antagonism caused a fall in supine and erect blood pressures. These falls were significantly greater than on either drug alone, and greater than the sum of the falls when taking the individual drugs. The combination of amlodipine and the ACE inhibitor was also additive. Both combinations with amlodipine were tolerated well by all patients. Conclusions: The combination of [alpha]-blockade and calcium antagonism has not previously been studied and should be useful for resistant hypertensives who have not tolerated P-blockade or ACE inhibitors. The combination of ACE inhibition and calcium antagonism has previously been shown to be additive; its use as a positive control in the present studies suggests that the use of an active drug for a run-in period may be a useful design for permitting the study of patients from whom all treatment cannot safely be withdrawn.