Very-low-dose combination of perindopril and indapamide: efficacy on blood pressure and target-organ damage.

Objective: To review the safety and efficacy of the very-low-dose combination of perindopril 2 mg and indapamide 0.625 mg (Per2/Ind0.625) in essential hypertension, in relation to blood pressure control and target-organ damage.
Study Selection: We included in this review several double-blind, randomized studies in hypertensive patients, including five main studies from the European registration file and two clinical trials on regression of target-organ damage [large artery stiffness: the Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind Study (REASON); microalbuminuria in patients with type 2 diabetes: the Preterax in Albuminuria Regression (PREMIER) study].
Main Outcome Measures: 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). Arterial stiffness, assessed from pulse wave velocity measurement and augmentation index (REASON study). Microalbuminuria (PREMIER study).
Results: The Per2/Ind0.625 combination was selected from the dose-finding studies. Twelve weeks after the participants were assigned to study groups, the reductions in SBP, measured with an OMRON device, were 12.3 +/- 15.0 mmHg with Per2/Ind0.625, 8.0 +/- 16.5 mmHg with perindopril 2 mg (P = 0.001), 9.4 +/- 14.3 mmHg with indapamide 0.625 mg (P = 0.023) and 2.1 +/- 16.8 mmHg with placebo (P < 0.001) (mean +/- SD; all P values are for comparisons with Per2/Ind0.625). 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 Per2/Ind0.625, perindopril 2 mg, indapamide 0.625 mg and placebo groups, respectively. During the long-term study, among 235 patients who achieved initial blood pressure normalization with the fixed combination, 79.8% sustained their normalized status over 1 year, with no significant difference regarding safety criteria. During the REASON study, Per/Ind reduced pulse wave velocity to a similar extent as atenolol, and augmentation index to a greater extent. During the PREMIER study, Per/Ind reduced microalbuminuria to a greater extent than did enalapril.
Conclusions: The proven efficacy on blood pressure and regression of target-organ damage with a good safety profile confirm that the new fixed-low-dose combination Per2/Ind0.625 is a valuable option in the first-line treatment of hypertension.