Blood pressure response, but not adverse event incidence, correlates with dose of angiotensin II antagonist

OBJECTIVE: To assess the efficacy and safety of the novel angiotensin II antagonist olmesartan medoxomil in patients with mild to moderate essential hypertension, using a meta-analysis of the combined database from seven US and European clinical trials. DESIGN: Studies were randomized, double-blind, placebo-controlled and dose-finding (2.5-80 mg), with treatment duration of 6-52 weeks. SETTING: Hospital outpatient clinics. PATIENT POPULATION: A total of 3,095 patients in the safety population and 3,055 patients in the intent-to-treat (efficacy) population. METHODS: All studies used conventional sphygmomanometry for blood pressure measurements at trough (end of the dosing interval). Three studies also used 24-h ambulatory blood pressure monitoring for the principal efficacy evaluations. MAIN OUTCOME MEASURES: Percentage of patients achieving diastolic blood pressure (DBP) < or = 90 mmHg or decrease > or = 10 mmHg (responder rate), percentage of patients achieving a target DBP < or = 90 mmHg or target systolic blood pressure (SBP) < or = 140 mmHg (normalization rate), and mean decrease in DBP from baseline to last visit. RESULTS: Efficacy variables tended to be dose related up to the 40 mg dose level. All olmesartan medoxomil doses were statistically significantly more effective than placebo for responder rate, DBP and SBP normalization rates, and mean decrease in DBP. A clinically relevant decrease of > or = 5 mmHg from baseline in sitting DBP was also observed at doses of 20 mg and above after correction for placebo effect The safety profile of olmesartan medoxomil was similar to that of placebo and was not dose related. CONCLUSIONS: Olmesartan medoxomil was safe and highly effective in lowering blood pressure in patients with mild to moderate essential hypertension in these studies.