A Double‐Blind, Randomized, Placebo‐Controlled Comparison of the Metabolic Effects of Low‐Dose Hydrochlorothiazide and Indapamide

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Abstract
To compare the metabolic effects of indapamide (I) and hydrochlorothiazide (HCTZ) at equivalent hypotensive doses, 11 hypertensive patients (5 male, 8 black, aged 56 ± 8 yr — mean ± SEM) having serum uric acid concentrations >8.0 mg/dL while receiving previous therapy with thiazides, received 28‐day courses of placebo, indapamide (2.5 mg/d), and HCTZ (25 mg/d) in randomized, double‐blind, double‐crossover design. Supine and standing blood pressures, weight, pulse rates and sera were obtained after each 28 day period. Blood pressures and weights were lowered (P <.001 and 0.01, respectively) equally by the diuretics: supine blood pressures fell from 168 ± 4/104 ± 2 (placebo) to 153 ± 4/93 ± 2 (HCTZ) and 155 ± 4/94 ± 2 mm Hg (I); standing blood pressures (after 2 minutes upright) also decreased: 171 ± 5/104 ± 2 (placebo) to 156 ± 5/93 ± 2 (HCTZ) and 157 ± 4/94 ± 2 mm Hg (I). There was a statistically significant difference (P <.05) across treatments by analysis of variance in both uric acid and potassium concentrations: serum urate (in mg/dL) was lowest with placebo (7.1 ± 0.3), and rose to 8.3 ± 0.2 with HCTZ (P <.001 compared with placebo by paired t test), and 8.1 ± 0.2 with I (P <.005 vs. placebo). The urate concentration with I was significantly lower than that with HCTZ (P <.02), but the magnitude of the difference was small (0.2 mg/dL). Serum potassium (mmol/L) was lower on each diuretic than that with placebo (4.2 ± 0.1, P <.005 for each), but not different between diuretics (HCTZ: 3.8 ±0.1; I: 3.9 ±0.1). No other significant differences were found in biochemical indices between therapies. Thus, at equihypotensive (i.e., low) doses in patients known to have elevated serum‐urate concentrations with thiazides, indapamide may cause less hyperuricemia than HCTZ. Although statistically significant, this difference is of questionable clinical importance, since both diuretics raise serum‐urate concentrations relative to placebo.