Aliskiren (SPP 100), an orally active renin inhibitor, has been shown to inhibit the production of angiotensin I and angiotensin II in healthy volunteers. In a pilot study, aliskiren decreased BP in hypertensive patients at daily doses of 75 and 150 mg. In this multi-centre, double-blind, active comparator trial, the dose-dependent effects of aliskiren were evaluated in 226 patients with mild to moderate hypertension. Parallel groups of randomized patients were assessed at the end of a washout period and again after a 4-week treatment period. Treatment consisted of single oral daily doses of aliskiren (37.5, 75, 150 or 300 mg) or of losartan 100 mg once daily. Daytime ambulatory systolic BP was defined as the primary variable of the study. As illustrated in the figure, a clear dose-response curve was observed for the decrease (mean +/- SEM) in daytime ambulatory systolic BP. The mean (SD) change at the end of the 4-week treatment period was -1.3 (9.5) mmHg, -5.5 (10.6) mmHg, -8.5 (10.4) mmHg, -10.5 (10.7) mmHg, and -11.1 (13.4) mmHg for 37.5, 75, 150, and 300 mg aliskiren and 100mg losartan, respectively. Statistically significant lowering occurred with 75, 150 and 300 mg of aliskiren. The daytime ambulatory systolic BP responses to aliskiren doses of 150 and 300 mg were not significantly different from that of 100 mg losartan. Similar results were shown for daytime ambulatory diastolic BP and for night-time ambulatory systolic and diastolic BP. Aliskiren was well tolerated - there was no increase in the number of adverse events with increasing doses of aliskiren, and the safety profile of aliskiren was similar to that of losartan. The results of this dose-ranging study confirm a dose-dependent reduction in BP with aliskiren in mild to moderate hypertension. Additional exploratory studies testing the efficacy and safety of this new renin inhibitor in patients with renal disease and congestive heart failure are currently underwa
