Aliskiren: Direct Renin Inhibitor. New Anti Hypertensive

(Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial, Prof Suzanne Oparil MD a , Steven A Yarows MD, The Lancet, The Lancet 2007; 370:221-229)

Q. What is Aliskiren and what is its role in hypertension ?

Aliskiren is the first orally available direct Renin inhibitor. The used earlier on Renin angiotensin system were ACE Inhibitors and Angiotensin receptor blockers. Aliskiren provides a new option in this pathway.

Q. Is combing ACE inhibitors and ARB useful ?

¬ Combining full doses of ACEI and ARBs has been tried in many studies including Val-HeFT, VALIANT, and CHARM

¬ The results of the same have been mixed.
¬ For example, CHARM-Added showed significant benefit of combining an ARB with ACE inhibitor treatment in patients with heart failure,
¬ whereas VALIANT showed no significant outcome benefit.
¬ Moreover, both trials showed that the combination therapies were less well tolerated than the respective monotherapies.
¬ Mechanistically, both ACE inhibitors and ARBs attenuate feedback inhibition of renin release by inhibiting the production or action of angiotensin II, resulting in increases in plasma renin concentration and plasma renin activity.

¬ Also the trials have showed that long-term dual renin system intervention with an ACE inhibitor and an ARB was associated with a higher rate of adverse events and an increased incidence of raised serum potassium and creatinine concentrations than was ACE inhibitor monotherapy.

Q. Is it a good idea to combine Aliskiren with ARBs ?

A recent trial published in LANCET combines Aliskiren and Valsartan (an ARB). The results according to the trial have been promising with minimal additional side effects. The authors recommended it to be better than coming ARB with ACEI.