AMLODIPINE AND LISINOPRIL IN COMBINATION FOR THE TREATMENT OF ESSENTIAL-HYPERTENSION - EFFICACY AND PREDICTORS OF RESPONSE

Objective: We have shown previously that the combination of captopril and nifedipine was effective at peak response but was very short acting. We therefore decided to study the longer-acting angiotensin converting enzyme inhibitor lisinopril and the long-acting calcium antagonist amlodipine, each alone and in combination, in a double-blind, randomized crossover study in which blood pressures were measured at peak and trough. This study provided the opportunity to investigate what parameters in these patients might possibly predict the fall in blood pressure with the individual drugs and with the combination. Methods: Fifteen patients with essential hypertension (eight male, 10 Caucasian; mean age 53 years) were studied. After 1 month observation on no treatment they were entered into a single-blind run-in of placebo given once a day for 1 month. Patients were then allocated randomly to amlodipine (5 mg once a day), lisinopril (10 mg once a day) or their combination (once a day) for 1 month in a double-blind crossover study. All patients were studied on their usual diet and no dietary advice was given. Blood pressure was measured by semi-automatic ultrasound sphygmomanometer both 24 h and 6 h (trough and peak) after the last dose. Results: During the crossover part of the study there was a significant additional blood pressure-lowering effect (at trough) of the combination compared with either amlodipine or lisinopril alone. Similar results were observed for the blood pressures at peak. The fall in blood pressure with lisinopril was related to baseline plasma renin activity, whereas when amlodipine was given, either alone or in combination, the fall in blood pressure was independent of baseline renin activity. The Blacks (n = 5) appeared not to respond as well to lisinopril as the Caucasians (n = 10). Finally, the blood pressure response to amlodipine tended to be associated with the severity of hypertension. Conclusions: The results of the present study indicate that: amlodipine and lisinopril in combination have a marked additional effect on blood pressure compared with either given as a monotherapy; their potentiation of action is long-acting; Black patients tend not to respond to the monotherapy with lisinopril as well as Caucasian patients, although they respond similarly to the combination; the response to amlodipine tends to be greater the higher the initial blood pressure; and, finally, the response to lisinopril is greater the higher the plasma renin activity.