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

Kurtz TW, Kajiya T - Vasc Health Risk Manag (2012)

Bottom Line: Greater antihypertensive effects of azilsartan might be due in part to its unusually potent and persistent ability to inhibit binding of angiotensin II to AT(1) 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 AT(1) receptors and/or reduction in BP.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, University of California, San Francisco, CA 94107, USA. kurtzt@labmed2.ucsf.edu

ABSTRACT
Azilsartan, an angiotensin II type 1 (AT(1)) 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 AT(1) 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 AT(1) 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 AT(1) 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.

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Related in: MedlinePlus

Time course of dissociation of azilsartan (circles), olmesartan (triangles), telmisartan (squares), and valsartan (diamonds) from human AT1 receptor preparations as reported by Ojima et al.42Notes: Membranes from Chinese hamster ovary cells expressing human AT1 receptors were preincubated for 90 minutes with each ARB and further incubated with radioactively labeled angiotensin II for 240 minutes in the presence of the drugs (solid symbols) or after washout of the drugs (open symbols). Each ARB was tested at a concentration of 30 nM except for valsartan which was tested at a concentration of 300 nM.
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f4-vhrm-8-133: Time course of dissociation of azilsartan (circles), olmesartan (triangles), telmisartan (squares), and valsartan (diamonds) from human AT1 receptor preparations as reported by Ojima et al.42Notes: Membranes from Chinese hamster ovary cells expressing human AT1 receptors were preincubated for 90 minutes with each ARB and further incubated with radioactively labeled angiotensin II for 240 minutes in the presence of the drugs (solid symbols) or after washout of the drugs (open symbols). Each ARB was tested at a concentration of 30 nM except for valsartan which was tested at a concentration of 300 nM.

Mentions: Time course studies of the ability of different ARBs to persistently block angiotensin II binding to AT1 receptors after drug washout have also indicated that azilsartan dissociates from AT1 receptors more slowly than other ARBs including olmesartan, telmisartan, and valsartan (Figure 4).42 These findings are consistent with separate studies conducted before and after drug washout indicating that azilsartan is more effective than other ARBs such as olmesartan or valsartan in persistently inhibiting angiotensin II-induced increases in BP,43 contraction of aortic vascular strips,42 cellular accumulation of inositol 1-phosphate,42 or activation of mitogen activated protein kinase (MAPK) in smooth muscle.57


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

Kurtz TW, Kajiya T - Vasc Health Risk Manag (2012)

Time course of dissociation of azilsartan (circles), olmesartan (triangles), telmisartan (squares), and valsartan (diamonds) from human AT1 receptor preparations as reported by Ojima et al.42Notes: Membranes from Chinese hamster ovary cells expressing human AT1 receptors were preincubated for 90 minutes with each ARB and further incubated with radioactively labeled angiotensin II for 240 minutes in the presence of the drugs (solid symbols) or after washout of the drugs (open symbols). Each ARB was tested at a concentration of 30 nM except for valsartan which was tested at a concentration of 300 nM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3295635&req=5

f4-vhrm-8-133: Time course of dissociation of azilsartan (circles), olmesartan (triangles), telmisartan (squares), and valsartan (diamonds) from human AT1 receptor preparations as reported by Ojima et al.42Notes: Membranes from Chinese hamster ovary cells expressing human AT1 receptors were preincubated for 90 minutes with each ARB and further incubated with radioactively labeled angiotensin II for 240 minutes in the presence of the drugs (solid symbols) or after washout of the drugs (open symbols). Each ARB was tested at a concentration of 30 nM except for valsartan which was tested at a concentration of 300 nM.
Mentions: Time course studies of the ability of different ARBs to persistently block angiotensin II binding to AT1 receptors after drug washout have also indicated that azilsartan dissociates from AT1 receptors more slowly than other ARBs including olmesartan, telmisartan, and valsartan (Figure 4).42 These findings are consistent with separate studies conducted before and after drug washout indicating that azilsartan is more effective than other ARBs such as olmesartan or valsartan in persistently inhibiting angiotensin II-induced increases in BP,43 contraction of aortic vascular strips,42 cellular accumulation of inositol 1-phosphate,42 or activation of mitogen activated protein kinase (MAPK) in smooth muscle.57

Bottom Line: Greater antihypertensive effects of azilsartan might be due in part to its unusually potent and persistent ability to inhibit binding of angiotensin II to AT(1) 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 AT(1) receptors and/or reduction in BP.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, University of California, San Francisco, CA 94107, USA. kurtzt@labmed2.ucsf.edu

ABSTRACT
Azilsartan, an angiotensin II type 1 (AT(1)) 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 AT(1) 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 AT(1) 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 AT(1) 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.

Show MeSH
Related in: MedlinePlus