Direct inhibition of renin as a cardiovascular pharmacotherapy: focus on aliskiren

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Nephrology

Background:

• The renin-angiotensin-aldosterone system (RAAS) plays a critical role in managing blood pressure and fluid balance.
• RAAS blockade is established for treating hypertension, heart failure, and diabetic kidney disease.
• Inhibiting the RAAS at its upstream point, via renin inhibition, offers theoretical advantages.

Purpose of the Study:

• To introduce aliskiren, a novel orally active, nonpeptide, specific human renin inhibitor.
• To evaluate aliskiren's efficacy in blocking renin activity and downstream RAAS components.
• To assess aliskiren's blood pressure-lowering effects and tolerability in hypertensive patients.

Main Methods:

• Preclinical studies in marmosets and rats to assess dose-dependent blood pressure reduction and renin activity blockade.
• Clinical trials in hypertensive patients to evaluate blood pressure-lowering efficacy compared to standard treatments.
• Assessment of adverse effects and tolerability at various doses.

Main Results:

• Aliskiren demonstrated dose-dependent blood pressure reduction in animal models.
• Aliskiren effectively inhibited plasma renin activity and downstream RAAS components.
• Clinical trials showed aliskiren's blood pressure-lowering efficacy comparable or superior to enalapril, losartan, irbesartan, and hydrochlorothiazide.
• Aliskiren was well tolerated with minimal adverse effects.

Conclusions:

• Aliskiren represents a new class of RAAS antagonists, offering a novel therapeutic modality.
• Aliskiren is effective and well-tolerated for lowering blood pressure in hypertensive patients.
• Further research may establish aliskiren's protective role in cardiovascular and renovascular diseases, as monotherapy or combination therapy.