A systematic review and meta-analysis of the efficacy and safety of a fixed, low-dose perindopril-indapamide combination as first-line treatment of hypertension

Background: A low-dose combination of perindopril and indapamide may effectively reduce blood pressure (BP) in hypertensive patients, but some factors related to study design might have contributed to the between group differences in the rate of reduction of BP observed in some trials. Objective: The aim of this study was to systematically assess the efficacy and safety profiles (through review of randomized, controlled trials) of the fixed, low-dose combination perindopril 2 mg and indapamide 0.625 mg given as I tablet daily as first-line antihypertensive therapy in patients with mild to moderate hypertension. Methods: We searched MEDLINE (1966-April 2003), EMBASE (1980-March 2003), BIOSIS (1999-December 2002), and the Cochrane Library, using the medical subject headings with the search terms perindopril, indapamide, hypertension, randomized controlled trials, randomly, random, randomization, perindopril-indapamide, essential hypertension, and primary hypertension. Additional articles were obtained from the reference lists of relevant reviews and papers. Results: We reviewed 11 trials (5936 individuals). In 5 studies of perindopril-indapamide versus placebo, the between-group weighted mean differences (WMDs) for both systolic and diastolic BP (SBP and DBP, respectively) favored perindopril-indapamide (SBP, -9.03 mm Hg [95% CI, -9.54 to -8.52]; DBP, -5.09 mm Hg [95% CI, -5.42 to -4.77] both P < 0.01 for z score for overall effect). In 6 studies of perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -3.72 mm Hg [95% Cl, -7.11 to 0.33], P = 0.03 for z score for overall effect; DBP -1.71 mm Hg [95% Cl, -2.27 to -1.16], P < 0.01 for z score for overall effect). Five studies compared perindopril-indapamide and placebo, in the remaining 3 studies, which assessed perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -4.00 mm Hg [95% Cl, -6.54 to -1.47], P < 0.01; DBP -1.02 mm Hg [95% Cl, -1.73 to -0.31], P < 0.01). Adverse events and withdrawals were not significantly different between perindopril-indapamide, placebo, or routine antihypertensive drugs. Conclusion: The studies in our analysis consistently demonstrated that a fixed, low-dose perindopril-indapamide combination has a favorable safety profile and may be efficacious as first-line treatment for patients with mild to moderate essential hypertension.