Dataset Information

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.

ABSTRACT:

Aim

The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population.

Methods

Two nested case-control studies were conducted in a cohort of 276?977 patients aged ?45 years initiating ACEIs from 2007 to 2014 in the UK Clinical Practice Research Datalink (CPRD). Cases of AE occurring for the first time during ACEI therapy (n = 416) were matched with AE-free controls (n = 4335) on the duration of ACEI treatment. Documented switches to angiotensin-II receptor blockers in the prescription records were used to identify ACEI-intolerance cases (n = 24?709), and these were matched with continuous ACEI users (n = 84?238) on the duration of ACEI therapy. Conditional logistic regression was used to assess the associations of demographic factors, comorbidities and comedication with AE and ACEI intolerance.

Results

AE during ACEI therapy was associated with age over 65 years [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.07, 1.73], history of allergy (OR 1.53, 95% CI 1.19, 1.96), use of calcium channel blockers (OR 1.57, 95% CI 1.23; 2.01), use of antihistamines (OR 21.25, 95% CI 16.44, 27.46) and use of systemic corticosteroids (OR 4.52, 95% CI 3.26, 6.27). ACEI intolerance was significantly associated with more comorbidities and comedication compared with AE, including allergy (OR 2.02, 95% CI 1.96, 2.09), use of antiasthmatic drugs (OR 1.51, 95% CI 1.42, 1.61) and use of antihistamines (OR 1.53, 95% CI 1.43, 1.63).

Conclusions

Among ACEI users developing AE or ACEI intolerance, several comorbidities and comedication classes were significantly more prevalent compared with ACEI users not developing these adverse reactions.

SUBMITTER: Mahmoudpour SH

PROVIDER: S-EPMC5099558 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.

Mahmoudpour Seyed Hamidreza SH Baranova Ekaterina Vitalievna EV Souverein Patrick C PC Asselbergs Folkert W FW de Boer Anthonius A Maitland-van der Zee Anke Hilse AH

British journal of clinical pharmacology 20161004 6

<h4>Aim</h4>The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population.<h4>Methods</h4>Two nested case-control studies were conducted in a cohort of 276 977 patients aged ≥45 years initiating ACEIs from 2007 to 2014 in the UK Clinical Practice Research Datalink (CPRD). Cases of AE occurring for the first time duri ...[more]

PMID: 27524468

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Project description:BackgroundThe use of angiotensin-converting enzyme inhibitors (ACEI) has been associated with the development of bradykinin-mediated angioedema. With ever-widening indications for ACEI in diseases including hypertension, congestive heart failure and diabetic nephropathy, a concomitant increase in ACEI-Angioedema (ACEI-A) has been reported. At present there is no validated severity scoring or discharge criteria for ACEI-A. We sought to develop and validate an investigator rating scale with corresponding discharge criteria using clinicians experienced in treating ACEI-A.MethodsIn-depth, 60-min qualitative telephone interviews were conducted with 12 US-based emergency physicians. Beforehand, clinicians were sent four case studies describing patients experiencing different severities of angioedema attacks. Clinicians were initially asked open-ended questions about their experience of patients' symptoms, treatment and discharge decisions. Clinicians then rated each patient case study and discussed patient diagnoses, ratings of symptom severity and discharge evaluation. The ratings were used to assess inter-rater reliability of the scale using the intra-class correlation coefficient (ICC) using IBM SPSS analysis Version 19 software.ResultsThe findings provide support focusing on four key symptoms of airway compromise scored on a 0-4 scale: 1) Difficulty Breathing, 2) Difficulty Swallowing, 3) Voice Changes and 4) Tongue Swelling and the corresponding discharge criteria of a score of 0 or 'No symptoms' for Difficulty Breathing and Difficulty Swallowing and a score of 0 or 1 indicating mild or absence of symptoms for Voice Change and Tongue Swelling. Eleven clinicians agreed the absence of standardized discharge criteria supported the use of this scale. All physicians concurred with the recommended discharge criteria. The clinician ratings provided evidence of strong inter-rater reliability for the rating scale (ICC > 0.80).ConclusionThe investigator rating scale and discharge criteria are clinically valid, relevant and reliable. Moreover, both address the current unmet need for standardized ED discharge criteria.

Project description:Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor-associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor-associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor-associated angioedema and 176 angiotensin-converting enzyme inhibitor-exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg(9)-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6+/-7.8 versus 29.6+/-7.3 nmol/mL per minute; P=0.026) and antigen (465.8+/-260.8 versus 563.1+/-208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor-associated angioedema compared with angiotensin-converting enzyme inhibitor-exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5+/-4.9 versus 29.8+/-6.7 nmol/mL per minute; P=0.001) and antigen (354.4+/-124.7 versus 559.8+/-163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.

Project description:Immunosuppressants decrease circulating dipeptidyl peptidase IV (DPPIV) activity in transplant patients, and decreased DPPIV activity has been associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. One study has reported an increased incidence of ACE inhibitor-associated angioedema among transplant patients compared to published rates, while several case series report angioedema in patients taking specific immunosuppressant agents.To test the hypothesis that transplant patients are at increased risk of ACE inhibitor-associated angioedema.We assessed the proportion of transplant patients in 145 cases with ACE inhibitor-associated angioedema and 280 ACE inhibitor-exposed controls. We measured the relationship between case-control status, transplant status, and immunosuppressant use and circulating DPPIV activity. We also assessed the incidence of angioedema among consecutive patients who underwent renal or cardiac transplant and were treated with an ACE inhibitor.Transplant patients were significantly overrepresented among ACE inhibitor-associated angioedema cases compared to controls (odds ratio 18.5, 95% CI 2.3-147.2, P = 0.0004). Immunosuppressant use, chronic renal failure, seasonal allergies and smoking were also associated with ACE inhibitor-associated angioedema in univariate analysis. The association of transplant status with ACE inhibitor-associated angioedema was no longer significant after inclusion of immunosuppressant therapy in a multivariate analysis. Dipeptidyl peptidase IV activity was significantly decreased in sera from cases compared to ACE inhibitor-exposed controls, as well as in individuals taking immunosuppressants. Two of 47 ACE inhibitor-treated renal transplant patients and one of 36 ACE inhibitor-treated cardiac transplant patients developed angioedema.Transplant patients are at increased risk of ACE inhibitor-associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.

Dataset Information

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.

Aim

Methods

Results

Conclusions

Publications

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.

Similar Datasets

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