Combination of enalapril and low-dose thiazide reduces normoalbuminuria in essential hypertension

OBJECTIVE: To examine the effect of the combination of enalapril with a very low dose of hydrochlorothiazide versus atenolol on urinary albumin excretion in normoalbuminuric patients with mild to moderate essential hypertension. A secondary objective was to compare the effects of the two regimens in patients with different levels of albuminuria. DESIGN: A 12 weeks, randomized, double-blind, double-dummy, multicenter, comparative study with two parallel groups. SETTING: General practices in Denmark and Finland. PATIENTS: The subjects comprised 174 patients with mild to moderate essential hypertension, normal serum creatinine and no proteinuria. INTERVENTIONS: Enalapril/hydrochlorothiazide (20/6 mg) daily or atenolol (50 mg) daily. MAIN OUTCOME MEASURES: Urinary albumin: creatinine ratio and blood pressure. RESULTS: At baseline, normoalbuminuria was found in 74 and 85 patients in the enalapril/hydrochlorothiazide and atenolol groups, respectively. Blood pressure was reduced similarly by both treatments. The ratio of urinary albumin to creatinine in normoalbuminuric patients was significantly reduced during treatment with enalapril/hydrochlorothiazide at 20/6 mg (from geometic mean x/divided by antilog SD of 0.53 x/divided by 1.77 to 0.47 x/divided by 1.58 mg/mmol, P=0.02) but was unchanged during atenolol treatment (0.55 x/divided by 1.74 and 0.58 x/divided by 1.87 mg/mmol). The difference between the two treatments was statistically significant (P=0.03) and was predominantly achieved through a reduction of albuminuria in the upper-normal range during enalapril/hydrochlorothiazide treatment. CONCLUSIONS: Therapy with enalapril/hydrochlorothiazide at 20/6 mg and atenolol at 50 mg once daily reduced blood pressure similarly in patients with essential hypertension. Suppression of urinary albumin excretion within the normoalbuminuric range was observed during treatment with enalapril/hydrochlorothiazide at 20/6 mg.