Efficacy and safety of eprosartan in severe hypertension

The efficacy of eprosartan, a highly selective, orally-active non-biphenyl, non-tetrazole, type 1 angiotensin II (ATI) receptor antagonist, was compar ed with that of the angiotensin-converting enzyme (ACE) inhibitor, enalapri l, with the addition of hydrochlorothiazide (HCTZ) when necessary in patien ts with severe hypertension (sitting diastolic blood pressure [sitDBP] grea ter than or equal to 115 mmHg and less than or equal to 125 mmHg). Patients (a = 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 wa s 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 greater tha n or equal to 90 mmHg. If blood pressure remained uncontrolled on maximum d oses 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 acce ptable 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 wa s the difference between treatments of the mean reduction from baseline in sitDBP at the end of the study. Eprosartan and enalapril caused a similar r eduction 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 decreas es in both sitting and standing systolic blood pressure (sitSBP and staSBP, respectively) than enalapril. The mean decrease in sitSBP was 29.1 mmHg fo r eprosartan compared with 21.1 mmHg for enalapril (p = 0.025). The mean re duction 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 e prosartan group and 54.2% in the enalapril group. The proportion of patient s in each treatment group who required addition of HCTZ was similar. Eprosa rtan was well tolerated; the overall incidence of adverse events was compar able to that in the enalapril group. These results demonstrate that in pati ents with severe hypertension, eprosartan is well tolerated and may be more effective than enalapril in reducing systolic blood pressure.