Tolerability and Efficacy of Fosinopril and Hydrochlorothiazide Compared with Amiloride and Hydrochlorothiazide in Patients with Mild to Moderate Hypertension

Summary

This 6-month multicentre, randomised, double-blind, parallel group clinical trial compared the tolerability and antihypertensive efficacy of a once-daily combination of fosinopril 20mg/hydrochlorothiazide 12.5mg (FOS/HCTZ) with a combination of amiloride 5mg/hydrochlorothiazide 50mg (AMI/HCTZ) in 217 patients with mild to moderate essential hypertension. Adverse events related to hypotension or to specifically targeted clinical laboratory values were observed infrequently with FOS/HCTZ compared with AMI/HCTZ: with FOS/HCTZ, only 4 of 104 patients (3.9%) experienced such events, compared with 16 of 113 (14.1%) in the AMI/HCTZ group (p < 0.001). While statistically significant differences were found between the two treatment groups for changes from baseline in serum potassium, cholesterol, triglyceride and glucose values, the metabolic profile was uniformly unfavourable towards the AMI/HCTZ group; for example, reductions in potassium and elevations in cholesterol, triglyceride and glucose were more pronounced with the AMI/HCTZ group than with the FOS/HCTZ group. Both antihypertensive regimens produced statistically significant reductions from baseline in seated diastolic blood pressure that were equivalent at most points of measurement during double-blind treatment. Therapeutic response rates were high (≥95%) and were similar for both regimens throughout the study. Because the relative risk for adverse events was markedly less over the long term with FOS/HCTZ than with AMI/HCTZ, the combination of fosinopril and hydrochlorothiazide may offer significant tolerability advantages over amiloride plus hydrochlorothiazide for such patients.