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 ad ditive with the other newer antihypertensives, namely alpha-blockers a nd angiotensin converting enzyme (ACE) inhibitors. Design: Three-way d ouble-blind, Latin-square crossover studies in two groups of 12 patien ts with essential hypertension. The three treatment periods were amlod ipine, 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 whic h the patients received a low dose of doxazosin (study A) or enalapril (study B) to enable recruitment of patients with moderate or severe h ypertension. Blood pressure, foot volume and plasma noradrenaline conc entration were measured at the end of each run-in and treatment period . Results: The combination of alpha-blockade and calcium antagonism ca used a fall in supine and erect blood pressures. These falls were sign ificantly greater than on either drug atone, and greater than the sum of the falls when taking the individual drugs. The combination of amlo dipine and the ACE inhibitor was also additive. Both combinations with amlodipine were tolerated well by all patients. Conclusions: The comb ination of alpha-blockade and calcium antagonism has not previously be en studied and should be useful for resistant hypertensives who have n ot tolerated beta-blockade or ACE inhibitors. The combination of ACE i nhibition and calcium antagonism has previously been shown to be addit ive; its use as a positive control in the present studies suggests tha t 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a run-in period may be a useful design for permitting the study of patients from whom all treatment cannot s afely be withdrawn.