Antihypertensive therapy with aliskiren

Aliskiren represents the first member in a new class of antihypertensive drugs. Inhibiting the renin-angiotensin system at its rate-limiting step is an idea that has been pursued for >30 years; however, earlier compounds failed because of problems related to efficacy, bioavailability, and/or side effects. Aliskiren, a 610 Da nonpeptide molecule, has exceptional affinity for the human renin enzymatic site and a half-life of about 40 h, which make its 3% bioavailability clinically unimportant with continued administration. The drug is not metabolized by CYP P450 enzymes and is excreted >90% unchanged by the fecal route. No adjustments are necessary for renal function, liver function, age, ethnicity, or other prescribed drugs. Blood pressure reductions are similar to those provided by other monotherapies. Interestingly, aliskiren combined with angiotensin receptor blocker or angiotensin-converting enzyme inhibitor therapy leads to a further blood pressure reduction as does combination with a diuretic or calcium channel blocker. The fact that plasma renin activity is reduced to low levels with aliskiren could provide a theoretical advantage over other treatments, while increases in total renin (prorenin) after the drug poses additional food for thought. Studies with primary cardiovascular and renal end points to address these possibilities are in progress.