cardiovascular-agents and Angioedema

During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin-angiotensin-aldosterone system (RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Cardiovascular Agents; Humans; Renin-Angiotensin System

Angioedema is characterized by swelling of the skin or mucous membranes. Overproduction of the vasodilator bradykinin (BK) is an important contributor to the disease pathology, which causes rapid increase in vascular permeability. BK formation on endothelial cells results from high molecular weight kininogen (HK) interacting with gC1qR, the receptor for the globular heads of C1q, the first component of the classical pathway of complement. Endothelial cells are sensitive to blood-flow-induced shear stress and it has been shown that shear stress can modulate gC1qR expression. This study aimed to determine the following: (1) how BK or angioedema patients' (HAE) plasma affected endothelial cell permeability and gC1qR expression under shear stress, and (2) if monoclonal antibody (mAb) 74.5.2, which recognizes the HK binding site on gC1qR, had an inhibitory effect in HK binding to endothelial cells. Human dermal microvascular endothelial cells (HDMECs) grown on Transwell inserts were exposed to shear stress in the presence of HAE patients' plasma. Endothelial cell permeability was measured using FITC-conjugated bovine serum albumin. gC1qR expression and HK binding to endothelial cell surface was measured using solid-phase ELISA. Cell morphology was quantified using immunofluorescence microscopy. The results demonstrated that BK at 1 µg/mL, but not HAE patients' plasma and/or shear stress, caused significant increases in HDMEC permeability. The mAb 74.5.2 could effectively inhibit HK binding to recombinant gC1qR, and reduce HAE patients' plasma-induced HDMEC permeability change. These results suggested that monoclonal antibody to gC1qR, i.e., 74.5.2, could be potentially used as an effective therapeutic reagent to prevent angioedema.

Topics: Angioedema; Antibodies, Monoclonal; Biomarkers; Bradykinin; Capillary Permeability; Cardiovascular Agents; Carrier Proteins; Endothelial Cells; Endothelium, Vascular; Humans; Mitochondrial Proteins; Permeability; Shear Strength

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Coronary Angiography; COVID-19; COVID-19 Nucleic Acid Testing; Drug Substitution; Humans; Male; Middle Aged; Myocardial Infarction; Patient Care Management; Platelet Aggregation Inhibitors; Ramipril; SARS-CoV-2; Treatment Outcome

To assess the required characteristics (cost, sensitivity and specificity) of a pharmacogenomic test for being a cost-effective prevention of angiotensin-converting enzyme inhibitors induced angioedema. Furthermore, we assessed the influence of only testing high-risk populations.. A decision tree was used.. With a willingness-to-pay threshold of €20,000 and €80,000 per quality adjusted life year, a 100% sensitive and specific test may have a maximum cost of €1.30 and €1.95, respectively. When only genotyping high-risk populations, the maximum test price would be €5.03 and €7.55, respectively.. This theoretical pharmacogenomic test is only cost-effective at high specificity, high sensitivity and a low price. Only testing high-risk populations yields more realistic maximum test prices for cost-effectiveness of the intervention.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cost-Benefit Analysis; Female; Humans; Male; Pharmacogenetics; Quality-Adjusted Life Years; Risk; Sensitivity and Specificity; Technology Assessment, Biomedical

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Humans; Male; Percutaneous Coronary Intervention; Photography

Despite its relatively common occurrence and life-threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic-mediated angioedema from bradykinin-mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin-mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM).

Topics: Airway Management; Angioedema; Cardiovascular Agents; Emergency Service, Hospital; Hospitalization; Humans; United States

Severe anaphylaxis in Hymenoptera venom allergy has been associated with a number of risk factors including elevation of baseline serum tryptase (BST), older age, concomitant diseases, and concurrent medication.. The aim of this study was to evaluate indicators and risk factors for severe anaphylaxis due to Hymenoptera field stings with an emphasis on details related to the sting reaction and concurrent medication.. In this single-center observational cohort study, we included 657 consecutive patients fulfilling the criteria for venom immunotherapy. Severity of sting-induced anaphylaxis was analyzed in relation to patient-specific risk factors (age and sex, preexisting cardiopulmonary conditions, cardiovascular medication) and details related to the sting reaction (culprit insect, localization of the sting, time interval to onset of symptoms, and presence or absence of cutaneous involvement). BST was determined in a subgroup of patients with moderate to severe anaphylaxis.. Four significant indicators and risk factors of severe anaphylaxis were identified (P < .001): (1) elevation of BST, (2) absence of urticaria or angioedema during anaphylaxis, (3) time interval of less than 5 minutes from sting to onset of symptoms, and (4) senior age. The absence of urticaria/angioedema is significantly related to BST elevation (P = .02). No relationship could be established between the severity of anaphylaxis and comorbidities or concurrent cardiovascular medication.. Absence of urticaria/angioedema is an indicator of severe anaphylaxis and possibly mastocytosis, requiring determination of BST. Study data do not provide evidence for an aggravation of sting-induced anaphylaxis by concurrent beta-blockade or angiotensin-converting enzyme inhibition.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anaphylaxis; Angioedema; Animals; Arthropod Venoms; Cardiovascular Agents; Child; Cohort Studies; Female; Humans; Hymenoptera; Insect Bites and Stings; Male; Middle Aged; Reaction Time; Risk Factors; Time Factors; Tryptases; Urticaria