Comparison of different therapeutic strategies in hypertension: a low-dose combination of perindopril/indapamide versus a sequential monotherapy or a stepped-care approach.
OBJECTIVE
To compare the efficacy and the tolerability of three different strategies in the treatment of hypertension (low-dose combination, sequential monotherapy and stepped-care).


METHODS
Hypertensive patients were randomized to a 9-month treatment with the aim to lower blood pressure below 140/90 mmHg. Treatment adjustments were allowed at months 3 and 6. The study was discontinued for patients with normal blood pressure at month 6. In the 'low-dose combination' group, perindopril (2 mg) and indapamide (0.625 mg) were first administered with the possibility to increase the doses in two steps up to respectively, 4 and 1.25 mg. In the 'sequential monotherapy' group, the treatment was initiated with atenolol (50 mg), replaced if necessary by losartan (50 mg), and then by amlodipine (5 mg). In the 'stepped-care' group, valsartan, was given first at a 40 mg dose, then at a 80 mg dose, to be co-administered finally if needed with hydrochlorothiazide, 12.5 mg. All study tablets were encapsulated to conceal their identity and had to be taken once a day.


METHODS
Patients with uncomplicated essential hypertension were recruited (n = 180 in the 'low-dose combination' group, n = 176 in the 'sequential monotherapy' group and n = 177 in the 'stepped-care' group).


RESULTS
The percentage of patients having achieved the target blood pressure was significantly greater in the 'low-dose combination' group (62%) than in the 'sequential monotherapy' (49%, P = 0.02) and the 'stepped-care' group (47%, P = 0.005). The percentage of patients having normalized their blood pressure without experiencing drug-related adverse events was also significantly higher in the 'low-dose combination' group (56%) than in the 'sequential monotherapy' (42%, P = 0.002) and the 'stepped-care' group (42%, P = 0.004).


CONCLUSIONS
A first line management of hypertension based on a low-dose combination of perindopril and indapamide allows the normalization of blood pressure in significantly more patients than a 'sequential monotherapy' strategy involving atenolol, losartan and amlodipine, and a 'stepped-care' strategy involving valsartan and hydrochlorothiazide. These better blood pressure results were not obtained at the expense of a worsening of tolerability.
Mourad
Jean-Jacques
JJ
Jean-Jacques Mourad, Department of Internal Medicine, Avicenne Hospital, Bobigny, France.
Waeber
Bernard
B
Zannad
Faïez
F
Laville
Maurice
M
Duru
Gérard
G
Andréjak
Michel
M
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007190:Indapamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D007190:Indapamide; D020913:Perindopril