Efficacy and Tolerability of Olmesartan Medoxomil Combined with Amlodipine in Patients with Moderate to Severe Hypertension after Amlodipine Monotherapy A Randomized, Double-Blind, Parallel-Group, Multicentre Study

Background and objectives: Cerebrovascular and cardiac adverse events can be significantly reduced by effective anti hypertensive therapy; however, BP control rates remain poor. The objective of this randomized, double-blind, parallel-group, multicentre study was to determine the efficacy and safety of olmesartan medoxomil/amlodipine combination therapy in patients with moderate to severe hypertension who had failed to respond to treatment with 8 weeks of open-label amlodipine. Methods: A total of 1017 patients entered the open-label amlodipine monotherapy stage; mean BP at week 0 was 164/102 mmHg. After 8 weeks of amlodipine monotherapy, (5 mg/day), non-responding patients (n = 755) were randomized to receive placebo plus amlodipine 5 mg or a combination of olmesartan medoxomil (10-40 mg) with amlodipine 5 mg for 8 weeks. At week 16, patients who had achieved diastolic BP (DBP) <90 mmHg and/or systolic BP (SBP) <140 mmHg continued on randomized treatment for a further 8 weeks. Patients in whom both SBP and DBP were >= 140/90 mmHg at week 16 had their medication uptitrated to olmesartan medoxomil/amlodipine 20/5 mg, olmesartan medoxomil/amlodipine 40/5 mg or olmesartan medoxomil/amlodipine 40/10 mg. Results: Combination of olmesartan medoxomil (10-40 mg) with amlodipine 5 mg for 8 weeks (double-blind) reduced mean SBP/DBP by up to 16.8 mmHg and 9.6 mmHg, respectively. The additional adjusted mean change in seated DBP (SeDBP) [primary endpoint] with last observation carried forward (LOCF) compared with placebo/amlodipine 5 mg was -2.0 mmHg (p = 0.0207), -3.7 mmHg (p < 0.0001) and -3.8 mmHg (p < 0.0001) for olmesartan medoxomil/amlodipine 10/5 mg, 20/5 mg and 40/5 mg, respectively. The corresponding additional adjusted mean change in SeSBP compared with placebo/amlodipine 5 mg was -3.5 mmHg (p = 0.0103), -5.8 mmHg (p < 0.0001) and -7.1 mmHg (p < 0.0001) for the olmesartan medoxomil/amlodipine 10/5 mg. 20/5 mg and 40/5 mg groups, respectively. Uptitration was associated with further mean reductions of up to 12.6 mmHg (SeSBP) and 8.2 mmHg (SeDBP), and allowed additional patients to achieve goal BP. Target BP was defined using both SBP and DBP criteria (patients without diabetes <140/90 mmHg; patients with diabetes <130/80 mmHg). More than 70% of patients on active combination therapy achieved their BP goal by week 24. All combination regimens were well tolerated. Conclusion: These results suggest that olmesartan medoxomil combined with amlodipine is effective and well tolerated in reducing BP in patients with moderate to severe hypertension.