Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients.
BACKGROUND
Additive hemodynamic effects of combined blockade of the renin-angiotensin system by an angiotensin I converting enzyme inhibitor and an angiotensin II antagonist have been observed in sodium-depleted normotensive volunteers and in patients with congestive heart failure.


OBJECTIVE
To investigate whether the same additive hemodynamic effects occur in patients with hypertension and to verify the safety of such an approach.


METHODS
Multicenter, randomized, double-blind, parallel-group, pilot study.


METHODS
177 patients with mild-to-moderate hypertension [diastolic blood pressure (DBP): 95-115 mmHg after a 4-week placebo run-in period] were included in the study.


METHODS
Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily was administered for 6 weeks. The effects of this therapeutic regimen was compared with similar groups of patients who received either 50 mg losartan daily or 10 mg enalapril daily.


METHODS
24-hour ambulatory mean DBP and clinic DBP measured at trough after 6 weeks of treatment.


RESULTS
24-hour ambulatory mean DBP did not significantly differ between treatment groups although the combination tended to lower BP more. The combination therapy was more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012], and more effective than enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28 patients, higher plasma active renin and angiotensin I levels during blockade by the combination therapy were observed. This finding confirmed that the combination of the two agents inhibited the renin-angiotensin system to a greater extent than did either agent alone.


CONCLUSIONS
A combination of 10 mg enalapril daily and 50 mg losartan daily safely induces a supplementary, although modest, fall in clinic DBP in patients with mild-to-moderate essential hypertension.
Azizi
M
M
Centre d'Investigations Cliniques 9201, Hôpital Broussais, Assistance Publique des Hôpitaux de Paris et INSERM, France. michel.azizi@brs.ap-hop-paris.fr
Linhart
A
A
Alexander
J
J
Goldberg
A
A
Menten
J
J
Sweet
C
C
Ménard
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan