Cor Vasa 2007, 49(11):408-414 | DOI: 10.33678/cor.2007.143

The new renin inhibitor aliskiren. The new drug blocking renin-angiotensin system. Will it meet the expectations?

Jiří Widimský

Klinika kardiologie, Institut klinické a experimentální medicíny, Subkatetra kardiologie IPVZ, Praha, Česká republika

Aliskiren is the first oral renin inhibitor. In healthy individuals, single and multiple doses of aliskiren result in peak plasma levels within 3-6 hours and the mean biological half-life after multiple doses is 40.7 ± 10.7 hours. It is just this long half-life which makes it possible to administer the drug once daily and ensures good blood pressure control even in the morning. It is eliminated mainly unchanged in feces. Only a small proportion (12%) of aliskiren is excreted during first-pass liver metabolism in the liver, with less than 10% of aliskiren excreted via the kidneys. Hence, no dose adjustments are necessary in patients with impaired hepatic and renal function.
Aliskiren is metabolized by cytochrome P450 only to a minimal extent and does not inhibit CYP isoenzymes. No interactions of aliskiren with warfarin, digoxin, hydrochlorothiazide, lovastatin, atenolol, celecoxib, cimetidine, ramipril, valsartan, metformin, and amlodipine have been reported. Aliskiren may negligibly reduce the bioavailablity of digoxin. Ketoconazole results in increases in plasma aliskiren levels by a factor of 1.8. When administered concomitantly with furosemide, the area under the curve (AUC) of furosemide was decreased; consequently, it is recommended to monitor furosemide effects.
In clinical trials, aliskiren administered once daily has been shown to reduce blood pressure in a way similar to standard doses of known AT1-receptor antagonists. The recommended starting dose of aliskiren is 150 mg. Additional benefit may be obtained by increasing the dose to 300 mg. However, as no further benefits have been shown with aliskiren at a dose 600 mg, this dose is not recommended for use in the clinical setting.
While patients with mild to moderate renal function impairment do not require dose adjustment, caution is to be exercised in patients with severe renal injury. No dose adjustments are needed in patients with impaired hepatic function.
Pooled data from eight randomized multicenter trials summarize the experience with aliskiren therapy in 8,570 hypertensive individuals. Therapy duration in these trials was 6-52 weeks. The data show aliskiren effectively reduces blood pressure independently of patient age or sex, is very well tolerated and can be effectively combined with the majority of other antihypertensive agents (hydrochlorothiazide, amlodipine, ramipril, valsartan).
As the antihypertensive action of aliskiren is not superior to that of AT1-receptor antagonists and, moreover, AT1-receptor antagonists are also well tolerated by patients, the results of ongoing trials are being awaited impatiently. The results should document the cardioprotective and nephroprotective efficacy of aliskiren and answer the main question, which is whether the potential cardioprotective and nephroprotective effects of aliskiren are superior to those already established for ACE inhibitors and AT1-receptor antagonists.
Definitive inclusion of aliskiren into the arsenal of antihypertensive agents will depend on the outcome of the above ongoing trials.

Keywords: Renin inhibitors; Aliskiren; Hypertension

Published: November 1, 2007  Show citation