Differential pharmacology and benefit/risk of azilsartan compared to other sartans

Abstract

Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), was recently approved by regulatory authorities for treatment of hypertension and is the 8th ARB to join the clinical market. This article discusses the medical reasons for introducing a new AT1 receptor blocker and reviews the experimental and clinical studies that have compared the functional properties of azilsartan to those of other ARBs. The main question addressed is: Does azilsartan have distinguishing features that should motivate choosing it over any of the other sartans for use in clinical practice? Based on studies conducted to date in hypertensive patients without serious comorbidities, azilsartan appears to be characterized by a superior ability to control 24-hour systolic blood pressure (BP) relative to other widely used ARBs including valsartan, olmesartan, and candesartan, and presumably others as well (eg, losartan). Compared to these other ARBs, azilsartan may increase the BP target control and response rate by an absolute value of 8%–10%. Greater antihypertensive effects of azilsartan might be due in part to its unusually potent and persistent ability to inhibit binding of angiotensin II to AT1 receptors. Preclinical studies have indicated that azilsartan may also have potentially beneficial effects on cellular mechanisms of cardiometabolic disease and insulin sensitizing activity that could involve more than just blockade of AT1 receptors and/or reduction in BP. However, the clinical relevance of these additional actions is unknown. Given that the general ability of antihypertensive drugs to protect against target organ damage is largely mediated by their ability to decrease BP, the enhanced antihypertensive effects of azilsartan should serve to justify clinical interest in this ARB relative to other molecules in the class that have a lower capacity to reduce BP.

Association Between Blood Pressure Lowering and Quality of Life by Treatment of Azilsartan

“…45) In the present study, switching from a conventional ARB to azilsartan also reduced both systolic and diastolic BP and improved some HR-QOL scores, especially in the geriatric depression. Given the multi-factorial characteristics of such mental conditions, it may be difficult to determine only one contributing factor.…”

Hypertension Therapeutics Update: A Brief Clinical Summary on Azilsartan, Cilnidipine and Nebivolol

“…4,5 For example, studies have demonstrated that azilsartan induces greater reductions in blood pressure compared to olmesartan which is considered as the most effective among the ARBs. 6,7 It appears that azilsartan is more effective than olmesartan and valsartan in the treatment of hypertension. Azilsartan provides 2 to 4 mm Hg further reduction in blood pressure compared to other ARBs.…”

Azilsartan alone and in combination for the treatment of hypertension – clinical utility and patient considerations

“…The tetrazole ring is replaced with a 5 member oxo-oxadiazole ring, which allows azilsartan to be less acidic and more lipophilic than candesartan. 6 Azilsartan medoxomil (AZL-M) is a prodrug derived from the chemical formula azilsartan kamedoxomil, the potassium salt formulation. It is rapidly hydrolyzed to the active metabolite, azilsartan, during the gastrointestinal absorption phase.…”