Daytime systolic ambulatory blood pressure with a two-step switch from candesartan to olmesartan monotherapy and the fixed-dose combination of olmesartan/amlodipine in patients with uncontrolled essential hypertension (SEVICONTROL-2).

The objective of this study was to investigate the efficacy of the fixed-dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single-arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug-related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.

Daytime systolic ambulatory blood pressure with a direct switch between candesartan monotherapy and the fixed-dose combination olmesartan/amlodipine in patients with uncontrolled essential hypertension (SEVICONTROL-1).

A direct switch of candesartan to the fixed-dose combination olmesartan/amlodipine in uncontrolled hypertension is a frequent clinical requirement but is not covered by current labeling. An open-label, prospective, single-arm phase IIIb study was performed in patients with 32 mg candesartan followed by olmesartan/amlodipine 40/10 mg. The primary endpoint was change in mean daytime systolic blood pressure (BP). Mean daytime systolic BP was reduced by 9.2±12.6 mm Hg (P<.0001) after substituting candesartan for olmesartan/amlodipine (baseline BP 140.2±9.7 mm Hg). The reduction in office BP was 9.4±18.4/4.0±9.6 mm Hg; P<.002). Overall, 61.3% of patients achieved a target BP <140/90 mm Hg using office BP and <135/85 mm Hg using ambulatory BP measurement. There were 8 adverse events with a possible relation to study drug and 1 unrelated serious adverse events. In conclusion, patients with uncontrolled moderate arterial hypertension being treated using candesartan monotherapy achieve a further reduction of BP when switched directly to a fixed-dose combination of olmesartan 40 mg/amlodipine 10 mg.

The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure: a prospective, randomized, controlled prevention trial of the German Hypertension League.

BACKGROUND: The prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure study addresses the issue of whether progression to manifest hypertension in patients with high-normal blood pressure can be prevented with treatment. METHODS: A total of 1008 participants with high-normal office blood pressure were randomized to ramipril treatment group (n = 505) and a control group (n = 503). The patients were followed up for 3 years. Primary endpoint was to prevent or delay the progression to manifest hypertension. Secondary endpoints were reduction in the incidence of cerebrovascular and cardiovascular events, as well as the development of hypertension as defined by ambulatory blood pressure monitoring. FINDINGS: One hundred and fifty-five patients (30.7%) in the ramipril group, and 216 (42.9%) in the control group reached the primary endpoint (relative risk reduction 34.4%, P = 0.0001). Ramipril also proved to be more effective in reducing the incidence of manifest office hypertension in patients with baseline ambulatory blood pressure monitoring high-normal blood pressure. The incidence of cerebrovascular and cardiovascular events showed no statistically significant differences between the two groups. Cough was more frequent in the ramipril group (4.8 vs. 0.4%). INTERPRETATION: There is now good clinical evidence that patients with high-normal blood pressure (prehypertension) are more likely to progress to manifest hypertension than patients with optimal or normal blood pressure. Additional ambulatory blood pressure monitoring seems to be essential to achieve correct diagnosis. Treatment of patients with high-normal office blood pressure with the angiotensin-converting enzyme inhibitor was well tolerated, and significantly reduced the risk of progression to manifest hypertension.