Fixed low-dose combination therapy in hypertension--a dose response study of perindopril and indapamide.
OBJECTIVE
To establish the optimal dose of the perindopril/indapamide combination (Per/Ind) in the treatment of mild or moderate hypertension.


METHODS
This was a randomized, double-blind, placebo-controlled, seven-way parallel-group, dose-ranging study, set in multicenter, outpatient offices/clinics in Europe and Canada.


METHODS
A total of 438 patients aged between 18 and 75 years whose supine diastolic blood pressure was between 95 and 114 mmHg were randomly assigned to an 8-week double-blind treatment with either placebo, Per 2/Ind 0.625, Per 4/Ind 1.25, Per 8/Ind 2.5, Per 0/Ind 1.25, Per 2/Ind 1.25 or Per 8/Ind 1.25 mg.


METHODS
Systolic and diastolic blood pressure measured in the clinic approximately 24 h after dosing.


RESULTS
There was a linear dose-response relationship (P<0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in supine diastolic blood pressure (-9.3 to -15.0 mmHg). Combining 1.25 mg Ind with increasing doses of Per (0, 2, 4 and 8 mg) also showed a linear dose-response relationship (P<0.001), with supine diastolic blood pressure falling by -8.0 to -12.0 mmHg compared with a fall of -5.2 mmHg for the placebo group. Similar findings were noted for supine systolic blood pressure, standing blood pressure and ambulatory blood pressure. Hypokalemia was more common (9.7%) in the Per 8/Ind 2.5 mg group than in the groups receiving other doses (0-4.6%).


CONCLUSIONS
The combinations of Per 2/Ind 0.625 mg and Per 4/Ind 1.25 mg were effective in reducing blood pressure without producing clinically important side effects.
Myers
M G
MG
Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Asmar
R
R
Leenen
F H
FH
Safar
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007190:Indapamide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000009:adverse effects / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D004338:Drug Combinations; D007190:Indapamide; D020913:Perindopril