This study compared the effects of aliskiren (a direct renin inhibitor), valsartan (an angiotensin receptor blocker), and their combination on blood pressure in patients with mild to moderate hypertension over 8 weeks. At 4 and 8 weeks: - All treatments reduced blood pressure more than placebo. - The greatest reductions in both systolic and diastolic blood pressure were seen with the combination of aliskiren and valsartan. - Both aliskiren and valsartan individually reduced blood pressure, but their combination appeared to have an additive effect.

1. Aliskiren and Valsartan for Antihypertensive Therapy Trial Presented at the American College of Cardiology Annual Scientific Session March 2007 Presented by Dr. Suzanne Oparil Aliskiren and Valsartan for Antihypertensive Therapy Trial

2. Aliskiren and Valsartan for Antihypertensive Therapy Trial: Background Valsartan is an angiotensin receptor blocker (ARB), and aliskiren is a new direct renin inhibitor that has just been approved by the US FDA. The goal of this trial was to evaluate treatment with aliskiren, valsartan, or the combination of the two compared with placebo among patients with mild to moderate hypertension. ACC 2007

3. Primary Endpoint: Reduction in mean sitting DBP Secondary Endpoint: Reduction in mean sitting SBP, response rate, achievement of blood pressure control (<140/90 mm Hg) 1797 patients of mean age 52 years with mild to moderate hypertension (diastolic blood pressure (DBP) > 95 and < 220 mm Hg) prior to randomization Placebo-controlled. Randomized. Blinded. Mean follow-up 8 weeks. 39% female. R mos. or yrs. follow-up Aliskiren and Valsartan for Antihypertensive Therapy Trial: Study Design 1-2 week period of washout from prior therapy and a 3-4 week run-in period Valsartan 160 mg n=455 Aliskiren + Valsartan 150 mg + 160 mg n=446 Placebo n=459 Aliskiren 150 mg n=437 Aliskiren 300 mg n=437 Valsartan 320 mg n=455 Aliskiren + Valsartan 300 mg + 320 mg n=446 Placebo n=459 4 weeks, double dosages 4 more weeks ACC 2007

4. Aliskiren and Valsartan for Antihypertensive Therapy: 4 Week Outcomes *p<0.0001 vs. placebo † p<0.001 vs. aliskiren/valsartan ACC 2007 Placebo Aliskiren + Valsartan Valsartan Aliskiren Week 4 Endpoint -10.7* -7.5* 150 mg n=437 -10.9* † -8.7* † 160 mg n=455 -15.3* -10.5* 150/160 mg n=446 -5.2 Change in SBP (mm Hg) -4.8 Change in DBP (mm Hg) n=459

5. Aliskiren and Valsartan for Antihypertensive Therapy: 8 Week Outcomes *p<0.0001 vs. placebo † p<0.001 vs. aliskiren/valsartan ACC 2007 -4.6 -17.2* -12.8* † -13.0* † Change in SBP (mm Hg) 16.5 49.3* 33.8 * † 37.4 * † BP Control Rate (%) Placebo Aliskiren + Valsartan Valsartan Aliskiren Week 8 Endpoint -9.0* † 300 mg n=437 -9.7* † 320 mg n=455 -12.2* 300/320 mg n=446 -4.1 Change in DBP (mm Hg) n=459

6. Aliskiren and Valsartan for Antihypertensive Therapy: Summary Among patients with mild to moderate hypertension, aliskiren, valsartan, and the combination of the two were associated with greater reductions in blood pressure compared with placebo at 8 wks, with the largest reductions seen in the combination group. Both aliskiren and valsartan are inhibitors of the renin-angiotensin-aldosterone system, but act at different points in the system, with aliskiren acting at the point of activation. ACC 2007

7. Aliskiren and Valsartan for Antihypertensive Therapy: Summary Both agents were effective in reducing blood pressure, but the combination of the two agents appeared to be additive. Work is ongoing into whether there will be improved organ protection with aliskiren alone and in combination. ACC 2007