Aliskiren as a novel therapeutic agent for hypertension and cardio-renal diseases

Abstract

Objectives High blood pressure (BP) is a major risk factor for cardiovascular and renal complications. A majority of treated hypertensive patients still complain of high BP. The renin-angiotensin aldosterone system (RAAS) has been a centre-stage target for all the cardiovascular and cardio-renal complications. Aliskiren, is the first direct renin inhibitor (DRI) to be approved by the US FDA. Renin controls the ratelimiting step in the RAAS cascade and hence is the most favorable target for RAAS suppression. Key findings This review article strives to summarize the pharmacokinetic, preclinical and clinical studies done so far pertaining to the efficacy of aliskiren. Further, the pharmacology of aliskiren has been comprehensively dealt with to enhance understanding so as to further research in this unfathomed area in the multitude of cardiovascular disorders and renal diseases. Summary Aliskiren has been shown to have comparable BP-lowering effects to other RAAS inhibitors. Recent clinical trials have indicated that it might contribute significantly in combination with other agents for the protection of end-organ diseases.

A Comparison of the Antihypertensive and Anti-Inflammatory Effects of Aliskiren and Ramipril Add-On Therapy in Peritoneal Dialysis Patients – A Pilot Open Label Study

“…Several clinical studies with aliskiren in hypertensive patients without renal impairment showed its satisfactory antihypertensive effects [6,11,12,18,[21][22][23][24]. The lack of a significant BP decrease in our study might have been due to several reasons including relatively well-controlled BP with conventional therapy at baseline and the dose of aliskiren Table 2.…”

“…Aliskiren is currently the only drug from this class. So far several studies have shown that aliskiren effectively decreases blood pressure with the side-effect profile similar to placebo [8,11,12]. Since aliskiren is excreted with bile and does not require dose reduction in case of decreased glomerular filtration rate it could become a preferred drug for the treatment of hypertension in end-stage kidney disease [10].…”

In Vitro Regulation of Enzymes of the Renin-angiotensin-aldosterone System by Isoquercitrin, Phloridzin and their Long Chain Fatty Acid Derivatives

“…While a large body of scientific data confirms independent renin inhibitory activity of linoleic acid [23][24][25] but there is no literature that provides strong support for the current results, showing α-linolenic acid ester as renin inhibitor. When compared to a clinical renin inhibitor, aliskiren (IC 50 0.6 nM), with bioavailability 2.6% [26] these esterified compounds may exhibit higher bioavailability leading to renin inhibition in vivo. Overall, the IC 50 values indicated a common feature in both series of compounds, i.e., the stronger renin inhibitory potential of esterified flavonoids.…”

Single-Dose Pharmacokinetics of the Renin Inhibitor ACT-077825 in Elderly and Young Subjects of Both Sexes

“…Unlike angiotensin-converting enzyme inhibitors, direct renin inhibitors act on a specific single target [5], showing the potential to block the renin-angiotensin-aldosterone system to a fuller extent [6]. The therapeutic benefit of direct renin inhibition has been well established for the treatment of hypertension, heart failure and nephropathy [7]. …”