Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema

Straßen, Ulrich; Baş, Murat; Wirth, Magdalena A.; Wirth, Markus; Gröger, Moritz; Stelter, Klaus; Volkenstein, Stefan; Kehl, Victoria; Kojda, Georg; Hoffmann, Thomas; Hahn, Janina; Trainotti, Susanne; Greve, Jens

doi:10.1016/j.ajem.2022.12.001

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…Several investigators attributed the angioedema induced by ACE inhibitors to the action of endogenous BK [89]; for instance, an increased blood concentration of the BK metabolite BK 1-5 was measured during such episodes [90]. However, such attacks did not respond to the administration of icatibant [68] or of a C1INH concentrate [75] in clinical settings that are comparable to HAE attacks for which these interventions are therapeutic. Possible explanations include a lack of involvement of the contact system in kinin generation, a prominent role for the kinin B1R or, simply, the lack of developing fluid extravasation when the therapies were initiated relatively late during such unexpected episodes.…”

Section: Other Application Of Kks Inhibitorsmentioning

confidence: 99%

Drugs of the Kallikrein–Kinin System: An Overview

Marceau

2023

DDC

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The kallikrein–kinin system consists of the two kininogen substrates present in the blood plasma, and two serine proteases: the plasma and tissue kallikreins. The action of the latter on kininogens produces small peptides, the kinins, short-lived, but endowed by powerful pharmacologic actions on blood vessels and other tissues. Many recent and exciting therapeutic developments in the field are briefly summarized. Notably, various novel strategies are being clinically developed to inhibit the formation of bradykinin or block its receptors in the management of hereditary angioedema. The interventions include orally bioavailable drugs, biotechnological proteins, and gene therapy. These approaches are currently explored in a variety of other inflammatory and thrombotic disorders. Harnessing controlled kinin formation is also of potential therapeutic interest, as shown by the clinical development of recombinant tissue kallikrein for ischemic stroke and renal disease. The biomarkers of kinin-mediated disorders, frequently implicating edemas, include the consumption of kininogen(s), plasma kallikrein activity, and the detection of circulating kinin metabolites such as fragments BK1–5 and BK2–9. Novel opportunities to clinically apply the underexploited drugs of the kallikrein–kinin system are briefly reviewed. This personal perspective is offered by an observer of and a participant in drug characterization throughout the last four decades.

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Section: Other Application Of Kks Inhibitorsmentioning

confidence: 99%

Drugs of the Kallikrein–Kinin System: An Overview

Marceau

2023

DDC

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“…Thirty patients (16 C1-INH, 14 placebo) were randomized and dosed. Regarding the results with a baseline application of steroids and antihistamines, C1-INH was inferior in the treatment of ACE-induced-angioedema when compared with a placebo with respect to the time to complete resolution of symptoms [125]. As most acute angioedema is often treated like "allergic" angioedema with corticosteroids and antihistamines, it remains unclear whether this treatment has at least a slight effect on acute bradykinin-mediated angioedema as a side effect of drugs such as ACE-inhibitors (see Section 6.5).…”

Section: C1-inhmentioning

confidence: 93%

Bradykinin-Mediated Angioedema Induced by Commonly Used Cardiovascular Drugs

Hahn,

Greve,

Bas

et al. 2023

DDC

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ACE inhibitors, sartans, and sacubitril are among the most important drugs for the prevention of cardiovascular mortality and morbidity. At the same time, they are known to cause non-allergic bradykinin-mediated angioedema, a potentially fatal swelling of the mucosa and/or submucosa and deeper skin without signs of urticaria or pruritus, occurring mainly in the head and neck region. In contrast with hereditary angioedema, which is also mediated by bradykinin, angioedema triggered by these drugs is by far the most common subtype of non-allergic angioedema. The molecular mechanisms underlying this type of angioedema, which are discussed here, are not yet sufficiently understood. There are a number of approved drugs for the prevention and treatment of acute attacks of hereditary angioedema. These include inhibitors of bradykinin synthesis that act as kallkrein inhibitors, such as the parenterally applied plasma pool, and recombinant C1 esterase inhibitor, ecallantide, lanadelumab, and the orally available berotralstat, as well as the bradykinin receptor type 2 antagonist icatibant. In contrast, no diagnostic tools, guidelines, or treatments have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced angioedema, although it is more common and can take life-threatening courses. Approved specific drugs and a structured diagnostic workflow are needed for this emergency diagnosis.

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“…However, in a double-blind, parallel group, multicenter randomized placebo-controlled trial of adult patients with ACE inhibitor-induced angioedema with airway obstruction, patients were randomized 1:1 for single doses of either C1INH or placebo (0.9% NaCl) intravenously, in addition to standard care. Surprisingly, the C1INH treatment was found to be inferior in the treatment of ACE inhibitor-induced angioedema compared to the placebo, specifically concerning the time to complete the resolution of symptoms (29.63 h ± 15.56 h in the C1INH arm and 17.29 h ± 10.40 h in the placebo arm) [ 76 ].…”

Section: Managementmentioning

confidence: 99%

Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition

Papapostolou,

Gregoriou,

Katoulis

et al. 2024

Pharmaceuticals

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Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACE inhibitor-induced angioedema (AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACE inhibitor-induced angioedema is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, early clinical recognition and discontinuation of the ACE inhibitors are the treatments of choice for the long-term management of ACE inhibitor- induced angioedema. The search period of the present review was set up until November 2023, and its aim is to shed light on the broader context of ACE inhibitor-induced angioedema, exploring aspects such as clinical presentation, pathophysiology, and therapeutic considerations in this potentially life-threatening condition. The exploration of alternative drug options such as angiotensin II receptor blockers, the potential association of coadministration of DPP-4 inhibitors with ACE inhibitors, the presentation of angioedema and the significant clinical importance of this condition are also discussed. By focusing on the chemical structure of ACE inhibitors, specifically their nitrogen-based heterocycles—an attribute shared by over 880 drugs approved by the FDA within the pharmaceutical industry—this review emphasizes the pivotal role of nitrogen scaffolds in drug design and underscores their relevance in ACE inhibitor pharmacology.

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Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema

Cited by 8 publications

References 31 publications

Drugs of the Kallikrein–Kinin System: An Overview

Drugs of the Kallikrein–Kinin System: An Overview

Bradykinin-Mediated Angioedema Induced by Commonly Used Cardiovascular Drugs

Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition

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