1. 1
Family Practice Guide to Oral
Renin Inhibitors (ORIs)
Objectives
• Review the Renin Angiotensin Aldosterone
System
• Discuss the role of antihypertensive medications
in regard to the RAAS
• Describe the history of renin inhibitors
• Highlight the advantages of aliskiren over other
previously developed renin inhibitors
• Identify patient populations in which ORIs would
benefit the most
• Explore future developments for ORIs
Renin Angiotensin Aldosterone
System
ACE
Ang I
Ang II
AT1 rec
Renin
Angiotensinogen
Medications
• Beta Blockers
– Decrease cardiac output
– Reduce sympathetic outflow
– Inhibit the release of renin
Medications
• ACEIs
– Inhibit formation of Ang II
– Increase bradykinin levels
– Vasodilation
– Sodium and water excretion
• ARBs
– Block AT1 receptors
– No increase in bradykinin
– Vasodilation
– Sodium and water excretion
Why these products sometimes
fail…
MULTIPLE PATHWAYS!!!

2. 2
Renin Inhibitors
• Benefits first outlined as early as 1957
• Early RIs were antibodies raised against
renin
• By late 1980s, several companies were
developing ORIs
– Low oral bioavailability
– Short half-life
– Weak BP-lowering activity
Renin Inhibitors
• 1995, aliskiren patented
– Twice as much oral bioavailability (still low)
– Much longer half-life
• New developments to find better
compounds
Patient Case
• 57 year old AAM
• PMH: obesity, HTN, T2DM
• Meds: Diovan/HCT 320/25 mg, metformin 1000
mg BID, ASA 81 mg QD, Lipitor 10 mg QD
• BP today: 152/96 mmHg
Is an ORI appropriate in this patient?
Is it appropriate?
• Aliskiren reduces BP an additional 23.5%
when combined with valsartan1
• Aliskiren reduces BP and additional 30%
when combined with HCTZ1
• Aliskiren was shown to reduce BP in six
randomized, double-blind, placebo-
controlled 8-week clinical trials. (see
package insert)
Patient Population Targets
• Aliskiren in Left-Ventricular Hypertrophy
trail – ALLAY4
• Aliskiren Observation of Heart Failure
Treatment trial – ALOFT5
• Aliskiren in the Evaluation of Proteinuria in
Diabetes trial – AVOID6
What’s in the future?
• Tekturna is not the end…
• Increased bioavailable compounds
• Beneficial effects on morbidity and
mortality?
• Specificity for human renin
• Efficacy

3. 3
References
1. Data on file. Clinical Development
SPP100A 2203. Novartis Pharmaceuticals
Corporation.
2. Staessen JA, Li Y, Ricahrt T. Oral renin
inhibitors. Lancet 2006; 368: 1449-56.
3. Tekturna package insert
4. http://clinicaltrials.gov [NCT00219141]
5. http://clinicaltrials.gov [NCT00219011]
6. http://clinicaltrials.gov [NCT00219206]