Clinical benefit of very-low-dose perindopril-indapamide combination in hypertension.
OBJECTIVE
To review the efficacy and safety of the very-low-dose combination of 2 mg perindopril and 0.625 mg indapamide in essential hypertension.


METHODS
The five main studies from the European registration file were performed in hypertensive outpatients and included two phase II double-blind randomised dose-ranging studies, and three phase III double-blind randomised studies (one study comparing placebo with each of the components, one long-term study over 15 months and one study comparing the combination and losartan).


METHODS
Decreases in systolic (SBP) and diastolic (DBP) blood pressures measured at trough with a mercury sphygmomanometer, an automatic device (Omron), and 24 h ambulatory blood pressure measurements (ABPM).


RESULTS
The combination 2 mg perindopril and 0.625 mg indapamide was selected from the dose-finding studies. Twelve weeks after participants in the randomised studies were allocated to groups, the reductions in SBP, measured with an Omron device, were 12.3 +/- 15.0 mmHg with the combination, 8.0 +/- 16.5 mmHg with 2 mg perindopril (P = 0.001), 9.4 +/- 14.3 mmHg with 0.625 mg indapamide (P = 0.023), and 2.1 +/- 16.8 mmHg with placebo (P < 0.001) (mean +/- SD; all P values are for comparisons with the combination). The reductions in DBP were 6.8 +/- 9.2 mmHg, 5.0 +/- 9.5 mmHg (P = 0.02), 4.7 +/- 8.2 mmHg (P = 0.004), and 2.4 +/- 9.6 mmHg (P < 0.001) in the combination, 2 mg perindopril, 0.625 mg indapamide and placebo groups, respectively. During the long-term study, among 235 patients who achieved initial blood pressure normalisation with the fixed combination, 79.8% sustained their normalisation over 1 year, with no significant difference regarding safety criteria: the occurrence of adverse drug reactions per patient per year was 0.37 and 0.28 in the combination and placebo groups, respectively. A significantly (P < 0.05) larger blood pressure decreasing effect on nocturnal mean SBP (by ABPM) was demonstrated for the combination compared with that achieved with losartan, with no difference in safety.


CONCLUSIONS
The proven efficacy on DBP and SBP, and the good safety profile, confirm that the new low-dose combination of 2 mg perindopril and 0.625 mg indapamide is a valuable option in the first-line treatment of hypertension.
Laurent
S
S
UNITE de Pharmacologie Clinique, Service de Pharmacologie, Hĵpital Européen Georges Pompidou, Paris, France. stephane-laurent@egp.ap-hop-paris.fr
D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007190:Indapamide / Q000008:administration & dosage* / Q000009:adverse effects; D019808:Losartan / Q000627:therapeutic use; D020913:Perindopril / Q000008:administration & dosage* / Q000009:adverse effects; D012449:Safety; D013997:Time Factors
D000959:Antihypertensive Agents; D007190:Indapamide; D019808:Losartan; D020913:Perindopril