Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension.

OBJECTIVE: To assess the antihypertensive efficacy and safety of the combination of the direct renin inhibitor aliskiren and ramipril in patients with diabetes and hypertension. METHODS: In this double-blind, multicentre trial, 837 patients with diabetes mellitus and hypertension (mean sitting diastolic blood pressure BP] > 95 and < 110 mmHg) were randomised to once-daily aliskiren (150 mg titrated to 300 mg after four weeks; n=282), ramipril (5 mg titrated to 10 mg; n=278) or the combination (n=277) for eight weeks. Efficacy variables were cuff mean sitting diastolic BP (msDBP) and mean sitting systolic BP (msSBP); 24-hour ambulatory BP, plasma renin activity (PRA) and plasma renin concentration (PRC) were also assessed. RESULTS: At week 8, aliskiren, ramipril and aliskiren/ramipril lowered msDBP (mean+/-SEM) by 11.3+/-0.5, 10.7+/-0.5 and 12.8+/-0.5 mmHg, and msSBP by 14.7+/-0.9, 12.0+/-0.9 and 16.6+/-0.9 mmHg, respectively. Aliskiren/ramipril provided superior msDBP reductions to ramipril (p=0.004) or aliskiren (p=0.043) monotherapy; adding aliskiren to ramipril provided an additional mean BP reduction of 4.6/2.1 mmHg. Aliskiren monotherapy was non-inferior to ramipril for msDBP reduction (p=0.0002) and superior for msSBP reduction (p=0.021). All treatments significantly lowered mean 24-hour ambulatory BP. Aliskiren significantly reduced PRA from baseline as monotherapy (by 66%, p<0.0001) or in combination with ramipril (by 48%, p<0.0001), despite large increases in PRC in all treatment groups. Aliskiren was well tolerated as monotherapy or in combination with ramipril. CONCLUSIONS: Combining aliskiren with ramipril provided a greater reduction in msDBP than either drug alone in patients with diabetes and hypertension.