Low-dose antihypertensive therapy with 1.5 mg sustained-release indapamide: results of randomised double-blind controlled studies. European study group.
OBJECTIVE
In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release (SR) formulation of indapamide was developed to optimize the drug's efficacy : safety ratio. The aim of this work was to evaluate the benefit of a low-dose diuretic by consolidating the efficacy and safety results of two clinical trials with a similar design.


METHODS
Clinical data were obtained in two European randomized double-blind studies with 690 mild to moderate hypertensive patients (95 mmHg < or = supine diastolic blood pressure < or = 114 mmHg using a mercury sphygmomanometer) treated respectively for 2 and 3 months, with a mean age of 53 and 57 years, 44 and 57% males, mean supine diastolic blood pressure of 100.6 and 102.5 mmHg and mean supine systolic blood pressure of 161.0 and 164.5 mmHg.


RESULTS
The first study, a dose-finding study with indapamide SR at 1.5, 2 and 2.5 mg versus placebo and the immediate-release (IR) formulation of indapamide, showed that the 1.5 mg dosage of the new indapamide formulation had an improved antihypertensive efficacy : safety ratio. The second study confirmed the equivalence of blood pressure reductions with 1.5 mg indapamide SR and 2.5 mg indapamide IR, and better acceptability with 1.5 mg indapamide SR, particularly in the number of patients with serum potassium levels < 3.4 mmol/l, which was reduced by more than 50%. The long-term efficacy of 1.5 mg indapamide SR was observed through a 9-month open-treatment follow-up to the second study.


CONCLUSIONS
The 1.5 mg SR formulation of indapamide has an improved antihypertensive efficacy : safety ratio, which is in accordance with international recommendations for the use of low-dose antihypertensive drugs and diuretics in first-line therapy of hypertension.
Ambrosioni
E
E
Divisione di Medicina Interna, Università degli studi di Bologna, Policlinico S. Orsola, Italy.
Safar
M
M
Degaute
J P
JP
Malin
P L
PL
MacMahon
M
M
Pujol
D R
DR
de Cordoüe
A
A
Guez
D
D
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000139:chemically induced; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000139:chemically induced; D003692:Delayed-Action Preparations; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007190:Indapamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011188:Potassium / Q000097:blood; D016683:Supine Position; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D007190:Indapamide; D011188:Potassium