Icatibant rapidly resolved ACE inhibitor–induced angioedema

Angioedema caused by ACE inhibitors resolved 70% more rapidly with icatibant than did standard therapy in a multicenter phase II study in Germany, which was reported online Jan. 29 in the New England Journal of Medicine.

Because of the increasing use of ACE inhibitors, approximately one-third of all cases of angioedema treated in emergency departments now are attributed to these agents. The current standard ED treatment of ACE inhibitor–induced angioedema is glucocorticoids plus antihistamines. However, patients generally don’t respond to this therapy, likely because this form of angioedema isn’t a histamine-mediated reaction. Instead, it is thought by some to be a bradykinin-mediated reaction, said Dr. Murat Bas of the department of otorhinolaryngology, Technische Universität München (Germany), and his associates.

Icatibant injections (Firazyr) are approved by the Food and Drug Administration for the treatment of acute attacks of hereditary angioedema in adults 18 years of age and older. The drug also is being studied in the United States for the treatment of ACE-inhibitor–induced angioedema.

Since ACE inhibitors interfere with the breakdown of bradykinin, and bradykinin-mediated hereditary angioedema is usually treated with bradykinin-receptor antagonists such as icatibant, the investigators performed a double-blind randomized trial comparing subcutaneous icatibant against standard treatment in 27 adults who presented to four German EDs during a 1.5-year period.

The primary endpoint – the time to complete resolution of ACE inhibitor–induced angioedema – was 8 hours with icatibant and 27 hours with standard therapy. Angioedema resolved within 4 hours in five patients (38%) given icatibant; none of the patients given standard therapy responded that quickly. The onset of symptom relief was 2 hours with icatibant and 12 hours with standard glucocorticoids plus antihistamines, a significant difference as judged by the study participants and the researchers. Also, the physician-assessed severity of angioedema began to abate within 1 hour of icatibant administration and within 8 hours for standard treatment (N. Engl. J. Med. 2015 Jan. 29 [doi:10.1056/NEJMoa1312524]).

“Although the sample size in this trial was too small to allow for a robust evaluation of safety, no patient discontinued participation in the study owing to adverse events,” Dr. Bas and his associates added.

Dr. Bas reported receiving grants and personal fees from Shire, the maker of icatibant, as did some of his associates.

Angioedema caused by ACE inhibitors resolved 70% more rapidly with icatibant than did standard therapy in a multicenter phase II study in Germany, which was reported online Jan. 29 in the New England Journal of Medicine.

Because of the increasing use of ACE inhibitors, approximately one-third of all cases of angioedema treated in emergency departments now are attributed to these agents. The current standard ED treatment of ACE inhibitor–induced angioedema is glucocorticoids plus antihistamines. However, patients generally don’t respond to this therapy, likely because this form of angioedema isn’t a histamine-mediated reaction. Instead, it is thought by some to be a bradykinin-mediated reaction, said Dr. Murat Bas of the department of otorhinolaryngology, Technische Universität München (Germany), and his associates.

Icatibant injections (Firazyr) are approved by the Food and Drug Administration for the treatment of acute attacks of hereditary angioedema in adults 18 years of age and older. The drug also is being studied in the United States for the treatment of ACE-inhibitor–induced angioedema.

Since ACE inhibitors interfere with the breakdown of bradykinin, and bradykinin-mediated hereditary angioedema is usually treated with bradykinin-receptor antagonists such as icatibant, the investigators performed a double-blind randomized trial comparing subcutaneous icatibant against standard treatment in 27 adults who presented to four German EDs during a 1.5-year period.

The primary endpoint – the time to complete resolution of ACE inhibitor–induced angioedema – was 8 hours with icatibant and 27 hours with standard therapy. Angioedema resolved within 4 hours in five patients (38%) given icatibant; none of the patients given standard therapy responded that quickly. The onset of symptom relief was 2 hours with icatibant and 12 hours with standard glucocorticoids plus antihistamines, a significant difference as judged by the study participants and the researchers. Also, the physician-assessed severity of angioedema began to abate within 1 hour of icatibant administration and within 8 hours for standard treatment (N. Engl. J. Med. 2015 Jan. 29 [doi:10.1056/NEJMoa1312524]).

“Although the sample size in this trial was too small to allow for a robust evaluation of safety, no patient discontinued participation in the study owing to adverse events,” Dr. Bas and his associates added.

Dr. Bas reported receiving grants and personal fees from Shire, the maker of icatibant, as did some of his associates.

Angioedema caused by ACE inhibitors resolved 70% more rapidly with icatibant than did standard therapy in a multicenter phase II study in Germany, which was reported online Jan. 29 in the New England Journal of Medicine.

Because of the increasing use of ACE inhibitors, approximately one-third of all cases of angioedema treated in emergency departments now are attributed to these agents. The current standard ED treatment of ACE inhibitor–induced angioedema is glucocorticoids plus antihistamines. However, patients generally don’t respond to this therapy, likely because this form of angioedema isn’t a histamine-mediated reaction. Instead, it is thought by some to be a bradykinin-mediated reaction, said Dr. Murat Bas of the department of otorhinolaryngology, Technische Universität München (Germany), and his associates.

Icatibant injections (Firazyr) are approved by the Food and Drug Administration for the treatment of acute attacks of hereditary angioedema in adults 18 years of age and older. The drug also is being studied in the United States for the treatment of ACE-inhibitor–induced angioedema.

Since ACE inhibitors interfere with the breakdown of bradykinin, and bradykinin-mediated hereditary angioedema is usually treated with bradykinin-receptor antagonists such as icatibant, the investigators performed a double-blind randomized trial comparing subcutaneous icatibant against standard treatment in 27 adults who presented to four German EDs during a 1.5-year period.

The primary endpoint – the time to complete resolution of ACE inhibitor–induced angioedema – was 8 hours with icatibant and 27 hours with standard therapy. Angioedema resolved within 4 hours in five patients (38%) given icatibant; none of the patients given standard therapy responded that quickly. The onset of symptom relief was 2 hours with icatibant and 12 hours with standard glucocorticoids plus antihistamines, a significant difference as judged by the study participants and the researchers. Also, the physician-assessed severity of angioedema began to abate within 1 hour of icatibant administration and within 8 hours for standard treatment (N. Engl. J. Med. 2015 Jan. 29 [doi:10.1056/NEJMoa1312524]).

“Although the sample size in this trial was too small to allow for a robust evaluation of safety, no patient discontinued participation in the study owing to adverse events,” Dr. Bas and his associates added.

Dr. Bas reported receiving grants and personal fees from Shire, the maker of icatibant, as did some of his associates.