An association has been shown between plasma renin activity (PRA) and the risk 
of cardiovascular disease. There is also evidence that angiotensin II exerts 
detrimental effects on progression and instabilization of atherosclerotic 
plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition 
of angiotensin I (Ang I) generation from angiotensinogen by direct renin 
inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I 
by angiotensin-converting enzyme inhibitors and finally by direct inhibition of 
the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor 
to reach the market, is a low-molecular-weight, orally active, hydrophilic 
nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration 
increases because the drugs blocks the negative feed-back exerted by Ang II on 
renin synthesis. Because of its long pharmacological half-life, aliskiren is 
suitable for once-daily administration. Its through-to-peak ratio approximates 
98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might 
offer the additional opportunity to inhibit progression of atherosclerosis at 
tissue level. Hypertension is an approved indication for this drug, which is 
also promising for the treatment of heart failure. The efficacy of this drug in 
reducing major clinical events is being tested in large ongoing clinical trials.