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 H type I 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] >= 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 >= 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 >= 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. 1 mm Hg with olmesartan medoxomil 40 mg/day, and a reduction of 10.8/7.9mm Hg with olmesartan medoxomil/thydrochlorothiazide 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.