Efficacy and Safety of Eprosartan in Severe Hypertension

Abstract

The efficacy of eprosartan, a highly selective, orally-active non-biphenyl, non-tetrazole, type 1 angiotensin II (AT1) receptor antagonist, was compared with that of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, with the addition of hydrochlorothiazide (HCTZ) when necessary in patients with severe hypertension (sitting diastolic blood pressure [sitDBP] > or = 115 mmHg and < or = 125 mmHg). Patients (n = 118) were randomized into an 8-week, double-blind titration phase and were started on oral eprosartan 400 mg total daily dose, given b.i.d., or oral enalapril 10 mg total daily dose, given o.d. The dose of eprosartan was increased to 600 and 800 mg daily, given b.i.d., and that of enalapril to 20 and 40 mg daily, given o.d., at weeks 2 and 4 if sitDBP was > or = 90 mmHg. If blood pressure remained uncontrolled on maximum doses of eprosartan or enalapril at week 6, HCTZ 25 mg o.d. was added to the treatment regimen. Patients whose blood pressure was deemed medically acceptable by the investigator at week 8 entered a 2-week maintenance phase on the final dose used in the titration phase. The primary efficacy measure was the difference between treatments of the mean reduction from baseline in sitDBP at the end of the study. Eprosartan and enalapril caused a similar reduction in sitDBP at study endpoint. The mean change in sitDBP at the end of the study for the eprosartan group was -20.1 mmHg vs -16.2 mmHg for the enalapril group. However, eprosartan produced significantly greater decreases in both sitting and standing systolic blood pressure (sitSBP and staSBP, respectively) than enalapril. The mean decrease in sitSBP was 29.1 mmHg for eprosartan compared with 21.1 mmHg for enalapril (p = 0.025). The mean reduction in staSBP was 27.8 mmHg for eprosartan compared with 20.0 mmHg for enalapril (p = 0.032). At the end of the study, the response rate (sitDBP < 90 mmHg or decreased from baseline by at least 15 mmHg) was 69.5% in the eprosartan group and 54.2% in the enalapril group. The proportion of patients in each treatment group who required addition of HCTZ was similar. Eprosartan was well tolerated; the overall incidence of adverse events was comparable to that in the enalapril group. These results demonstrate that in patients with severe hypertension, eprosartan is well tolerated and may be more effective than enalapril in reducing systolic blood pressure.