Efficacy and tolerability of olmesartan medoxomil in patients with mild to moderate essential hypertension: the OLMEBEST Study.

BACKGROUND AND OBJECTIVE: Achieving target BP is important to control the increased cardiovascular risk associated with uncontrolled hypertension. However, failure to respond to therapy is common with all classes of antihypertensive agents. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) possess many of the positive features of angiotensin-converting enzyme inhibitors, with fewer adverse effects. However, many patients fail to respond adequately to low-dose monotherapy. This study examined whether olmesartan medoxomil dose titration and olmesartan medoxomil/hydrochlorothiazide combination therapy were therapeutically equivalent in patients with mild to moderate essential hypertension who had shown an inadequate response to low-dose olmesartan medoxomil monotherapy.

METHODS: This was a prospective, parallel group, partially randomised, double-blind study set in 463 centres in nine European countries. 2306 male and female adult patients aged 18-75 years with mild to moderate essential hypertension (sitting diastolic BP [DBP] > or =90mm Hg and <110mm Hg) were enrolled. All enrolled patients received open-label olmesartan medoxomil 20mg once daily for 8 weeks. At the end of this period, patients whose BP had not normalised (sitting DBP > or =90mm Hg) were randomised to receive olmesartan medoxomil monotherapy (40mg once daily, n = 302) or olmesartan medoxomil (20mg once daily)/hydrochlorothiazide (12.5mg once daily) combination therapy (n = 325) for 4 weeks. The main outcome measure was change in mean sitting DBP during randomised treatment.

RESULTS: After 8 weeks of open-label treatment with olmesartan medoxomil 20 mg/day, 76% of patients showed a DBP response (sitting DBP <90mm Hg or reduction of > or =10mm Hg). During the randomised phase of the study, both treatments were associated with further improvements in sitting SBP/DBP: a reduction of 5.3/5.1mm Hg with olmesartan medoxomil 40 mg/day, and a reduction of 10.8/7.9mm Hg with olmesartan medoxomil/hydrochlorothiazide combination therapy. Final mean BPs of 145.3/90.9mm Hg (olmesartan medoxomil 40 mg/day) and 140.7/88.7mm Hg (olmesartan medoxomil 20mg + hydrochlorothiazide) were achieved, compared with a mean BP of 160.8/100.5mm Hg at baseline. The two treatments were not therapeutically equivalent. Sitting DBP showed a response and was normalised (<90mm Hg) in 62% and 47% of olmesartan medoxomil monotherapy patients, respectively. In the combination therapy group, these endpoints were achieved by 71% (response) and 59% (normalisation) of patients. Treatment with olmesartan medoxomil 40 mg/day was associated with a lower frequency of adverse events than olmesartan medoxomil/hydrochlorothiazide combination therapy (21.5% vs 28.3%, respectively).

CONCLUSION: For patients who did not achieve adequate BP control after initial treatment with olmesartan medoxomil 20 mg/day, olmesartan medoxomil dose titration (to 40 mg/day) or addition of hydrochlorothiazide (12.5 mg/day) elicited a sitting DBP response in the majority of patients who had failed to respond to low-dose monotherapy, and normalisation of sitting DBP in approximately 50% of patients. Both these strategies represent effective and well tolerated treatment options in patients who show an inadequate response to low-dose monotherapy with olmesartan medoxomil.