Angioedema due to the renin inhibitor aliskiren

To the Editor: The interesting report by Korniyenko and colleagues of the delayed diagnosis of visceral angioedema due to angiotensin-converting enzyme (ACE) inhibitor therapy¹ should alert readers that a long duration of use of ACE inhibitors should not rule out the diagnosis of ACE inhibitor-induced angioedema, as symptoms can be delayed for up to a decade.

Risk factors for angioedema for patients on ACE inhibitor therapy that have been identified so far include black race, the XPNPEP2 C-2399A polymorphism in men (which leads to decreased aminopeptidase P activity),² and concomitant use of the mTOR inhibitors sirolimus (Rapamune) or everolimus (Afinitor) in renal transplant recipients.³ All of these factors further decrease metabolism of the vasoactive peptide bradykinin. However, the effect of cofactors such as use of nonsteroidal anti-inflammatory drugs, aspirin, simvastatin, estrogen, or a tendency for angioedema (such as in patients with recurrent or episodic idiopathic angioedema) on lowering the threshold for angioedema or increasing the severity of the angioedema episode or episodes after starting ACE inhibitor therapy remains unknown.

Physicians should also be aware of angioedema as a significant side effect of the new renin inhibitor aliskiren (marketed by Novartis Pharmaceuticals as Rasilez in the United Kingdom and as Tekturna in the United States) for treatment of essential hypertension.⁴ A pooled analysis of 31 studies in 12,188 patients showed the incidence of angioedema associated with aliskiren monotherapy to be 0.4%, similar to that with ACE inhibitors: relative risk 0.31, 95% confidence interval 0.07–1.47 for 150 mg; relative risk 0.57, 95% confidence interval 0.17–1.89 for 300 mg).⁵ However, no patients were hospitalized with a serious angioedema event.

Although the mechanism of action of aliskiren via renin inhibition would suggest that bradykinin may not be the causative agent of angioedema, physicians should ensure that patients who report significant angioedema episodes or those who present with angioedema have their medication history thoroughly reviewed to prevent a serious untoward event.

To the Editor: The interesting report by Korniyenko and colleagues of the delayed diagnosis of visceral angioedema due to angiotensin-converting enzyme (ACE) inhibitor therapy¹ should alert readers that a long duration of use of ACE inhibitors should not rule out the diagnosis of ACE inhibitor-induced angioedema, as symptoms can be delayed for up to a decade.

Risk factors for angioedema for patients on ACE inhibitor therapy that have been identified so far include black race, the XPNPEP2 C-2399A polymorphism in men (which leads to decreased aminopeptidase P activity),² and concomitant use of the mTOR inhibitors sirolimus (Rapamune) or everolimus (Afinitor) in renal transplant recipients.³ All of these factors further decrease metabolism of the vasoactive peptide bradykinin. However, the effect of cofactors such as use of nonsteroidal anti-inflammatory drugs, aspirin, simvastatin, estrogen, or a tendency for angioedema (such as in patients with recurrent or episodic idiopathic angioedema) on lowering the threshold for angioedema or increasing the severity of the angioedema episode or episodes after starting ACE inhibitor therapy remains unknown.

Physicians should also be aware of angioedema as a significant side effect of the new renin inhibitor aliskiren (marketed by Novartis Pharmaceuticals as Rasilez in the United Kingdom and as Tekturna in the United States) for treatment of essential hypertension.⁴ A pooled analysis of 31 studies in 12,188 patients showed the incidence of angioedema associated with aliskiren monotherapy to be 0.4%, similar to that with ACE inhibitors: relative risk 0.31, 95% confidence interval 0.07–1.47 for 150 mg; relative risk 0.57, 95% confidence interval 0.17–1.89 for 300 mg).⁵ However, no patients were hospitalized with a serious angioedema event.

Although the mechanism of action of aliskiren via renin inhibition would suggest that bradykinin may not be the causative agent of angioedema, physicians should ensure that patients who report significant angioedema episodes or those who present with angioedema have their medication history thoroughly reviewed to prevent a serious untoward event.

To the Editor: The interesting report by Korniyenko and colleagues of the delayed diagnosis of visceral angioedema due to angiotensin-converting enzyme (ACE) inhibitor therapy¹ should alert readers that a long duration of use of ACE inhibitors should not rule out the diagnosis of ACE inhibitor-induced angioedema, as symptoms can be delayed for up to a decade.

Risk factors for angioedema for patients on ACE inhibitor therapy that have been identified so far include black race, the XPNPEP2 C-2399A polymorphism in men (which leads to decreased aminopeptidase P activity),² and concomitant use of the mTOR inhibitors sirolimus (Rapamune) or everolimus (Afinitor) in renal transplant recipients.³ All of these factors further decrease metabolism of the vasoactive peptide bradykinin. However, the effect of cofactors such as use of nonsteroidal anti-inflammatory drugs, aspirin, simvastatin, estrogen, or a tendency for angioedema (such as in patients with recurrent or episodic idiopathic angioedema) on lowering the threshold for angioedema or increasing the severity of the angioedema episode or episodes after starting ACE inhibitor therapy remains unknown.

Physicians should also be aware of angioedema as a significant side effect of the new renin inhibitor aliskiren (marketed by Novartis Pharmaceuticals as Rasilez in the United Kingdom and as Tekturna in the United States) for treatment of essential hypertension.⁴ A pooled analysis of 31 studies in 12,188 patients showed the incidence of angioedema associated with aliskiren monotherapy to be 0.4%, similar to that with ACE inhibitors: relative risk 0.31, 95% confidence interval 0.07–1.47 for 150 mg; relative risk 0.57, 95% confidence interval 0.17–1.89 for 300 mg).⁵ However, no patients were hospitalized with a serious angioedema event.

Although the mechanism of action of aliskiren via renin inhibition would suggest that bradykinin may not be the causative agent of angioedema, physicians should ensure that patients who report significant angioedema episodes or those who present with angioedema have their medication history thoroughly reviewed to prevent a serious untoward event.