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A current evaluation of the safety of angiotensin receptor blockers and direct renin inhibitors.

Siragy HM - Vasc Health Risk Manag (2011)

Bottom Line: Less is known about the safety of the direct renin inhibitor aliskiren, which was approved as an antihypertensive in 2007.ARBs are generally well tolerated, with no known class-specific adverse events.An ongoing safety investigation by the FDA has not concluded that ARBs increase the risk of cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, and Hypertension Center, University of Virginia Health System, Charlottesville, VA 22908, USA. hms7a@virginia.edu

ABSTRACT
The safety of angiotensin II receptor blockers (ARBs) for the treatment of hypertension and cardiovascular and renal diseases has been well documented in numerous randomized clinical trials involving thousands of patients. However, recent concerns have surfaced about possible links between ARBs and increased risks of myocardial infarction and cancer. Less is known about the safety of the direct renin inhibitor aliskiren, which was approved as an antihypertensive in 2007. This article provides a detailed review of the safety of ARBs and aliskiren, with an emphasis on the risks of cancer and myocardial infarction associated with ARBs. Safety data were identified by searching PubMed and Food and Drug Administration (FDA) Web sites through April 2011. ARBs are generally well tolerated, with no known class-specific adverse events. The possibility of an increased risk of myocardial infarction associated with ARBs was suggested predominantly because the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial reported a statistically significant increase in the incidence of myocardial infarction with valsartan compared with amlodipine. However, no large-scale, randomized clinical trials published after the VALUE study have shown a statistically significant increase in the incidence of myocardial infarction associated with ARBs compared with placebo or non-ARBs. Meta-analyses examining the risk of cancer associated with ARBs have produced conflicting results, most likely due to the inherent limitations of analyzing heterogeneous data and a lack of published cancer data. An ongoing safety investigation by the FDA has not concluded that ARBs increase the risk of cancer. Pooled safety results from clinical trials indicate that aliskiren is well tolerated, with a safety profile similar to that of placebo. ARBs and aliskiren are well tolerated in patients with hypertension and certain cardiovascular and renal conditions; their benefits outweigh possible safety concerns.

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Overview of the renin-angiotensin system.Reproduced with permission of the American Society of Nephrology, from ‘The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease’, Volpe et al, volume 13, supplement 3, 2002; permission conveyed through Copyright Clearance Center, Inc.3Abbreviations: ACE, angiotensin-converting enzyme; AT1/AT2, angiotensin type 1/2.
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f1-vhrm-7-297: Overview of the renin-angiotensin system.Reproduced with permission of the American Society of Nephrology, from ‘The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease’, Volpe et al, volume 13, supplement 3, 2002; permission conveyed through Copyright Clearance Center, Inc.3Abbreviations: ACE, angiotensin-converting enzyme; AT1/AT2, angiotensin type 1/2.

Mentions: Key steps in the RAS are shown in Figure 1.3 Following conversion from its precursor prorenin, the aspartate protease renin is secreted by granular cells of the juxtaglomerular apparatus in the kidney.3,19 The biosynthesis and release of renin are key elements in determining the capacity of the RAS to regulate BP and respond to fluid changes.3 Renin catalyzes the conversion of angiotensinogen to angiotensin I, which is the rate-limiting step in the RAS.15 DRIs block this step and reduce plasma renin activity.15 ACE catalyzes the conversion of angiotensin I to angiotensin II, and ACE inhibitors block this step in the RAS.15 Angiotensin II binds to angiotensin II type-1 (AT1) receptors, which regulates BP via several mechanisms and provides feedback inhibition of further release of renin by the kidneys.15 ARBs block the AT1 receptor, reducing the effects of angiotensin II.4


A current evaluation of the safety of angiotensin receptor blockers and direct renin inhibitors.

Siragy HM - Vasc Health Risk Manag (2011)

Overview of the renin-angiotensin system.Reproduced with permission of the American Society of Nephrology, from ‘The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease’, Volpe et al, volume 13, supplement 3, 2002; permission conveyed through Copyright Clearance Center, Inc.3Abbreviations: ACE, angiotensin-converting enzyme; AT1/AT2, angiotensin type 1/2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104607&req=5

f1-vhrm-7-297: Overview of the renin-angiotensin system.Reproduced with permission of the American Society of Nephrology, from ‘The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease’, Volpe et al, volume 13, supplement 3, 2002; permission conveyed through Copyright Clearance Center, Inc.3Abbreviations: ACE, angiotensin-converting enzyme; AT1/AT2, angiotensin type 1/2.
Mentions: Key steps in the RAS are shown in Figure 1.3 Following conversion from its precursor prorenin, the aspartate protease renin is secreted by granular cells of the juxtaglomerular apparatus in the kidney.3,19 The biosynthesis and release of renin are key elements in determining the capacity of the RAS to regulate BP and respond to fluid changes.3 Renin catalyzes the conversion of angiotensinogen to angiotensin I, which is the rate-limiting step in the RAS.15 DRIs block this step and reduce plasma renin activity.15 ACE catalyzes the conversion of angiotensin I to angiotensin II, and ACE inhibitors block this step in the RAS.15 Angiotensin II binds to angiotensin II type-1 (AT1) receptors, which regulates BP via several mechanisms and provides feedback inhibition of further release of renin by the kidneys.15 ARBs block the AT1 receptor, reducing the effects of angiotensin II.4

Bottom Line: Less is known about the safety of the direct renin inhibitor aliskiren, which was approved as an antihypertensive in 2007.ARBs are generally well tolerated, with no known class-specific adverse events.An ongoing safety investigation by the FDA has not concluded that ARBs increase the risk of cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, and Hypertension Center, University of Virginia Health System, Charlottesville, VA 22908, USA. hms7a@virginia.edu

ABSTRACT
The safety of angiotensin II receptor blockers (ARBs) for the treatment of hypertension and cardiovascular and renal diseases has been well documented in numerous randomized clinical trials involving thousands of patients. However, recent concerns have surfaced about possible links between ARBs and increased risks of myocardial infarction and cancer. Less is known about the safety of the direct renin inhibitor aliskiren, which was approved as an antihypertensive in 2007. This article provides a detailed review of the safety of ARBs and aliskiren, with an emphasis on the risks of cancer and myocardial infarction associated with ARBs. Safety data were identified by searching PubMed and Food and Drug Administration (FDA) Web sites through April 2011. ARBs are generally well tolerated, with no known class-specific adverse events. The possibility of an increased risk of myocardial infarction associated with ARBs was suggested predominantly because the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial reported a statistically significant increase in the incidence of myocardial infarction with valsartan compared with amlodipine. However, no large-scale, randomized clinical trials published after the VALUE study have shown a statistically significant increase in the incidence of myocardial infarction associated with ARBs compared with placebo or non-ARBs. Meta-analyses examining the risk of cancer associated with ARBs have produced conflicting results, most likely due to the inherent limitations of analyzing heterogeneous data and a lack of published cancer data. An ongoing safety investigation by the FDA has not concluded that ARBs increase the risk of cancer. Pooled safety results from clinical trials indicate that aliskiren is well tolerated, with a safety profile similar to that of placebo. ARBs and aliskiren are well tolerated in patients with hypertension and certain cardiovascular and renal conditions; their benefits outweigh possible safety concerns.

Show MeSH
Related in: MedlinePlus