A comparison of blood lipid and blood pressure responses during the treatment of systemic hypertension with indapamide and with thiazides

Thiazide diuretics in high dosage adversely affect the lipid profile. The non-thiazide indoline, indapamide, appears to be free of this effect, but it is unclear whether this apparent metabolic advantage of indapamide is superior to thiazides used in low dose. Since there are no large direct comparative studies to test this distinction, I surveyed the literature and pooled the findings of all published reports giving data on both lipid and blood pressure effects of thiazides in various doses and of indapamide, 2.5 mg daily, used as monotherapy of hypertension. I found 31 reports of thiazides; 12 of them examined low-dose regimens, i.e., less than or equal to 25 mg/day of hydrochlorothiazide or its equivalent in other thiazides. Larger doses of thiazides were tested in 19 studies (median daily dose of 50 mg, maximum dose of 112.5 mg). There were 430 subjects in the low-dose studies and 559 subjects in the high-dose regimens. There were 13 studies of indapamide, comprising 558 subjects. Regarding lipids, total cholesterol increased from baseline by 1.4% on indapamide, 3.8% on low-dose thiazides, and 6.3% on high-dose thiazides. The change from baseline was significantly greater for high-dose thiazides than for indapamide (p <0.01). Changes in high-density lipoprotein cholesterol did not differ among groups. The change in triglycerides differed among regimens, -0.5%, 10.8%, and 19.5% for indapamide, low-dose thiazides, and high-dose thiazides, respectively (p <0.01). Systolic blood pressure (SBP) decreased by 13 and 18 mm Hg on low-dose and high-dose thiazides, respectively (p <0.05 between doses). Indapamide lowered SEP by 16 mm Hg, not different from either thiazide dose. Diastolic blood pressure did not differ among groups. From these noncomparative studies, I conclude that (1) indapamide has no adverse lipid effect and lowers blood pressure equally to thiazides; (2) thiazide effects on lipids and SEP are dose-dependent; and (3) thiazides adversely affect the lipid profile even in low dose.