Antihypertensive efficacy and safety of Olmesartan Medoxomil and Ramipril in elderly mild to moderate essential hypertensive patients with or without metabolic syndrome: A pooled post Hoc analysis of two comparative trials

Background: Two recent identically designed trials (one Italian and one European multinational) have compared the head-to-head efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil and the angiotensin converting enzyme inhibitor ramipril, in elderly patients with essential hypertension. Objective: The aim of the present study was to assess the antihypertensive efficacy of olmesartan and ramipril in elderly patients with hypertension, with or without metabolic syndrome, by performing a pooled analysis of data from the two head-to-head trials. Methods: After a 2-week, placebo wash-out, 1,453 treated or untreated elderly hypertensive patients aged 65-89 years [with sitting office diastolic blood pressure (DBP) 90-109 mmHg and/or sitting office systolic BP (SBP) 140-179 mmHg] were randomized to 12-weeks of double-blind treatment with olmesartan 10 mg or ramipril 2.5 mg once daily. Treatment could be up-titrated to 20 and 40 mg for olmesartan, and 5 and 10 mg for ramipril, after the first 2 and 6 weeks, respectively, in patients with inadequately controlled BP (BP ≥140/90 mmHg for non-diabetics and ≥130/80 mmHg for diabetics). Office BP was measured at randomization and after 2, 6 and 12 weeks of treatment. 24-h ambulatory BP recordings were obtained at randomization and after 12 weeks. Results: Of the 1,426 patients in the intent-to-treat analysis, 735 (51.5 %) had metabolic syndrome (olmesartan, n = 372; ramipril, n = 363). After 12 weeks of treatment, baseline-adjusted office BP reductions were greater (p <0.05) with olmesartan (SBP 17.0 mmHg; 95 % CI 18.4, 15.6; DBP 9.6 mmHg; 95 % CI 10.4, 8.8) than with ramipril (SBP 14.7 mmHg; 95 % CI 16.1, 13.2; DBP 8.4 mmHg; 95 % CI 9.2, 7.6) in patients with metabolic syndrome. In these patients, BP normalization rates were also greater with olmesartan than with ramipril (46.0 vs. 35.8 %, p <0.01). Similarly, in patients without metabolic syndrome, the antihypertensive efficacy of olmesartan was also significantly (p <0.05) better than that of ramipril. In the subgroup of patients with valid ambulatory BP (ABP) recordings and metabolic syndrome (olmesartan, n = 182; ramipril, n = 170), the reduction in mean 24-h ABP was greater with olmesartan (SBP 10.2 mmHg; 95 % CI 11.8, 8.6; DBP 6.6 mmHg; 95 % CI 7.5, 5.6) than with ramipril (SBP 8.5 mmHg; 95 % CI 10.2, 6.9; DBP 4.7 mmHg; 95 % CI 5.7, 3.7), with a statistically significant (p <0.01) difference for the DBP comparison. The proportion of patients experiencing drug-related adverse events was comparable in patients with (olmesartan 2.4 % vs. ramipril 2.8 %) and without (3.5 vs. 3.7 %) metabolic syndrome. Conclusions: Olmesartan provides more effective BP control than ramipril in elderly hypertensive patients with and without metabolic syndrome.