Safety and tolerability of an olmesartan medoxomil-based regimen in patients with stage 1 hypertension: a randomized, double-blind, placebo-controlled study.

Background: One of the reasons for suboptimal blood pressure (BP) control in patients with hypertension is poor adherence to treatment, which may be caused by treatment-emergent adverse events. Therefore, it is crucial for an antihypertensive agent to provide a high level of efficacy without compromising tolerability. Objective: To evaluate the safety and tolerability of a titrate-to-goal, olmesartan medoxomil-based therapy in patients with stage 1 hypertension (seated systolic BP [SeSBP] of 140–159 mmHg or seated diastolic BP [SeDBP] of 90–99 mmHg). Methods: This was a pre-specified analysis of data from a randomized, double-blind, placebo-controlled, multicentre (29 sites) clinical study conducted from January to October 2007 in the US. Male and female patients (n= 130) aged ≥18 years with stage 1 hypertension were included in the analysis. Patients were treated with either placebo or an olmesartan medoxomil-based titration regimen, which comprised treatment with olmesartan medoxomil plus hydrochlorothiazide (HCTZ) as required to achieve a target BP of <120/80mmHg. The current analysis focused on the safety of olmesartan medoxomil in patients with stage 1 hypertension, particularly in terms of discontinuation rates and the incidence of dizziness and orthostatic hypotension. Safety and tolerability were assessed throughout the study. The primary efficacy outcome was the least-squares (LS) mean change from baseline in SeSBP after 12 weeks double-blind treatment. Additional efficacy variables included LS mean change from baseline in SeDBP at 12 weeks and the proportions of patients achieving BP goals at study end and at each titration step. Results: In patients with stage 1 hypertension, the olmesartan medoxomil-based regimen was generally well tolerated at all titration steps, and discontinuation due to adverse events was similar between olmesartan medoxomil and placebo. Treatment-emergent adverse events occurred in 16.1% up to 27.6% of olmesartan medoxomil recipients and between 8.3% and 24.3% of placebo recipients, across treatment regimens; a slight increase in the incidence of treatment-emergent adverse events was observed with olmesartan medoxomil/HCTZ versus olmesartan medoxomil alone (≤27.6% vs ≤19.3%). In addition, one or more drug-related events were reported in up to 10.3% of olmesartan medoxomil recipients and up to 5.7% of placebo recipients. Gastrointestinal disorders (≤10.0%), nervous system disorders (≤10.3%), and infections/infestations (≤7.1%) were the most commonly reported treatment-emergent adverse events in the olmesartan medoxomil treatment group. The most common nervous system disorders in the olmesartan medoxomil treatment group were dizziness (≤6.9%) and headache (≤5.4%). Orthostatic hypotension was not reported. The LS mean differences between olmesartan medoxomil and placebo for change from baseline in SeSBP (−22.0 mmHg; 95% confidence interval [CI] −26.9, −17.3) and SeDBP (−12.2mmHg; 95% CI −14.9, −9.4; both p<0.0001) significantly favoured olmesartan medoxomil at week 12 with last observation carried forward. At study end, a BP goal of <140/90mmHg was achieved by 81.0% of patients in the olmesartan medoxomil group versus 43.1% of patients in the placebo group (p<0.0001). Conclusion: Olmesartan medoxomil-based therapy was well tolerated in this study among patients with stage 1 hypertension and demonstrated a placebo-like safety and tolerability profile. This regimen was also effective in terms of BP lowering and enabling patients to achieve BP goals without an adverse effect on tolerability.