Potentiation of the antihypertensive effect of enalapril by randomized addition of different doses of hydrochlorothiazide.
The purpose of this study was to evaluate the potentiating effect of hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily when added in a placebo-controlled double-blind randomized study of patients with essential hypertension, whose diastolic blood pressure (DBP) was not adequately controlled (DBP > 90 mmHg) following 6 weeks of single-blind treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril, 20 mg once daily. Forty-eight patients started the first period with enalapril after 4 weeks on placebo. In 13 patients DBP fell to < or = 90 mmHg after enalapril for 6 weeks. In this group supine mean arterial pressure (MAP) was reduced by 13% (P < 0.01). In the patients whose DBP was > 90 mmHg after 6 weeks on enalapril (n = 32) the average supine MAP fell by 9% (P < 0.001). After 3 weeks there was no further drop in blood pressure (BP). Addition of HCTZ to the 32 patients with DBP > 90 mmHg caused a significant further drop in supine BP by 13/7 mmHg with 12.5 mg and by 15/7 mmHg with 25 mg. Seven patients discontinued the study, none due to side effects on enalapril alone. Well-being, assessed with a special questionnaire, was significantly better with enalapril as monotherapy compared with previous treatment, but not different from well-being during the placebo periods. It is concluded that 20 mg enalapril once daily lowered BP effectively and was well tolerated. The maximum BP lowering effect was seen within 3 weeks. Addition of HCTZ caused a significant, and clinically relevant, further drop in BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Dahlöf
B
B
Department of Medicine, Ostra Hospital, University of Gothenburg, Sweden.
Andrén
L
L
Eggertsen
R
R
Jern
S
S
Svensson
A
A
Hansson
L
L
D000328:Adult; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method
D006852:Hydrochlorothiazide; D004656:Enalapril