Comparison of Increase in the Enalapril Dose and Addition of Hydrochlorothiazide as Second-Step Treatment of Hypertensive Patients Not Controlled by Enalapril Alone

Abstract

Forty-six patients were randomly allocated to two different groups of treatment if their diastolic blood pressure remained above 90 mm Hg after one month of treatment with 20 mg enalapril mg once daily. In the first group (ENA), 23 patients were given higher daily dosages of enalapril (40 mg and, when necessary, 60 mg). The second group of 23 patients (HCTZ) was given 20 mg/day enalapril and hydrochlorothiazide (25 mg/day and, when necessary, 50 mg). Blood pressure was measured by an automatic device and by the physician with a standard sphygmomanometer. Blood pressure was significantly lower in the HCTZ group, according to both the automatic device (130 .+-. 9/80 .+-. 8 vs. 141 .+-. 5/86 .+-. 8 mm Hg, p < 0.01/p < 0.05) and the sphygmomanometer (134 .+-. 10/89 .+-. 6 vs. 149 .+-. 16/94 .+-. 5 mm Hg, p < 0.001/p < 0.01). Plasma renin activity, increased by enalapril at the 20 mg dosage, rose in the HCTZ group but not in the ENA group (22.4 .+-. 22 vs. 10.2 .+-. 11 pmol/ml/h, p < 0.05). Plasma aldosterone increased significantly in the HCTZ group (.044 .+-. 0.22 vs. 0.30 .+-. 0.17 pmol ml. p < 0.05) but did not change in the ENA group (0.31 .+-. 0.1-vs 0.30 .+-. 0.17 pmol/ml, NS). In the ENA group, converting enzyme activity was not reinforced (5.7 .+-. 8 vs. 6.6 .+-. 6 mU/ml, NS) despite an increase in plasma enalapril at levels (172.4 .+-. 10.8 vs. 72.1 .+-. 42 ng/ml, p < 0.001). Plasma potassium fell in the HCTZ group (-0.43 .THETA. 0.3 mmol/L, p < 0.001), and was not affected by the higher doses taken by ENA group (+ 0.11 .+-. 0.3 mmol/L). The effects of converting enzyme inhibition by enalapril 20 mg o.d. are not reinforced by the administration of 40-60 mg o.d., whereas the addition of hydrochlorothiazide 25-50 mg o.d. decreases blood pressure simultaneously with a rise in plasma renin and aldosterone. Combined therapy with enalapril and hydrochlorothiazide is a more effective antihypertensive approach than increased doses of enalapril.