ALTITUDE will determine whether dual RAAS blockade with the direct renin inhibitor aliskiren in combination with an ACEi or ARB will reduce major morbidity and mortality in a broad range of high-risk patients with type 2 diabetes.

No abstract

Background-Diuretics are recommended as first-line agents for the treatment of hypertension. This randomized, double-blind, multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension. Methods and Results-After a 2-to 4-week placebo run-in, 1124 patients (mean sitting diastolic blood pressure [BP] 95 to 109 mm Hg) were randomized to aliskiren 150 mg (nϭ459), hydrochlorothiazide 12.5 mg (nϭ444), or placebo (nϭ221) once daily. Forced titration (to aliskiren 300 mg or hydrochlorothiazide 25 mg) occurred at week 3; at week 6, patients receiving placebo were reassigned (1:1 ratio) to aliskiren 300 mg or hydrochlorothiazide 25 mg. From week 12, amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled. Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method. BP reductions (mean sitting systolic BP/mean sitting diastolic BP) were significantly greater with aliskirenversus hydrochlorothiazide-based treatment at week 26 (Ϫ20.

Introduction: Diuretics are recommended as first-line agents for the treatment of hypertension. This double-blind, multicentre study compared the long-term efficacy and safety of the direct renin inhibitor aliskiren (ALI) and the diuretic hydrochlorothiazide (HCTZ) in patients with hypertension. Methods: After a 2-week washout and 2-4-week placebo (PBO) run-in, 1124 patients (mean age 55.9 years) with hypertension (mean sitting diastolic blood pressure [msDBP] 95-109mmHg) were randomised to ALI 150 mg (n=459), HCTZ 12.5 mg (n=444), or PBO (n=221) once daily for 3 weeks followed by forced titration to ALI 300 mg or HCTZ 25 mg for 23 weeks; at week 6, patients receiving PBO were reassigned (1:1 ratio) to ALI 300 mg or HCTZ 25 mg for 20 weeks. Amlodipine (AML) 5 mg was added from week 12 and titrated to 10 mg from week 18 for patients with BP>140/90mmHg. Results: At week 26, the ALI group (n=560) had significantly greater reductions from baseline than the HCTZ group (n=547) in msDBP (14.2 vs 13.0 mmHg; p<0,05). Conclusions: Aliskiren-based therapy is well tolerated and provides greater BP reductions than HCTZ-based therapy that are sustained over 26 weeks in patients with hypertension. Aliskiren monotherapy is superior to HCTZ monotherapy in lowering BP.