Blood Pressure-Lowering Efficacy of Amiloride versus Enalapril as Add-On Drugs in Patients with Uncontrolled Blood Pressure Receiving Hydrochlorothiazide

Abstract

A large proportion of patients with hypertension need a second drug to reach satisfactory control of blood pressure (BP), but there are few well-designed controlled trials comparing the efficacy of drugs added as a second option. In a double-blind randomized clinical trial, 82 patients with uncontrolled BP, receiving hydrochlorothiazide 25 mg daily, were selected to receive amiloride 2.5–5 mg/day (n = 39) or enalapril 10–20 mg/day (n = 43). Ambulatory blood pressure monitoring (ABPM) was done before and after 12-weeks of treatment. Office BP was measured in the 4^th, 8^th, and 12^th weeks. The doses of amiloride and enalapril were doubled in the fourth week, and propranolol was added in the 8th week if office BP was above 140/90 mm Hg. There was a greater BP reduction in patients treated with enalapril. The ABPM δ values between the groups were 3.6 ± 2.2, 3.9 ± 2.2, and 1.1 ± 2.7 mmHg for 24-h, daily, and nightly systolic blood pressure, respectively, favoring enalapril. For diastolic blood pressure (DBP), the deltas were 1.7 ± 2.0, 3.2 ± 1.5, and 1.2 ± 1.9 mmHg, respectively (p = 0.039 for daily DBP). Office SBP decreased more and sooner in patients allocated to enalapril (p = 0.003). More patients taking amiloride required propranolol to control BP (p = 0.035). Potassium increased 0.3 mEq/L on the average in both groups. Cough, albeit predominantly mild, was reported more frequently by participants treated with enalapril. We conclude that enalapril is more effective than amiloride to lower BP of patients on hydrochlorothiazide with uncontrolled BP.

Trial registration: ClinicalTrials.gov identifier: NCT00394394.

Keywords:

• hypertension
• amiloride
• enalapril
• pharmacological treatment
• ambulatory blood pressure monitoring