Clinical Profile of Angioedema Associated With Angiotensin Converting-Enzyme Inhibition

Slater, Eve E.; Merrill, Debora; Guess, Harry A.; Roylance, Peter J.; Cooper, Warren D.; Inman, W. H. W.; Ewan, P. W.

doi:10.1001/jama.1988.03410070095035

Cited by 309 publications

(137 citation statements)

References 18 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Cough and angioedema, two adverse drug reactions typically associated with ACE-inhibition and two of the major causes of withdrawal from ACE-inhibitor trials, are usually more frequently observed in women than in men [12], [13]. In our study, the incidence of cough, was similar between men and women treated with zofenopril, and ramipril, while it occurred more frequently in lisinopril-treated women, suggesting an intra-class difference.…”

Section: Discussionsupporting

confidence: 51%

“…However, an Australian study evidences a decrease in CV events in men but not in women [11]. Furthermore, cough and angioedema are more frequent in women than in men during treatment with ACE-inhibitors [12], [13]. Notably, men but not women with the XPNPEP2 C-2399A genotype, characterized by high plasma levels of aminopeptidase inactivated metabolites, are susceptible versus ACE-inhibitors [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Treatment with Zofenopril in Men and Women with Acute Myocardial Infarction: Gender Analysis of the SMILE Program

et al. 2014

View full text Add to dashboard Cite

Backgroundthe SMILE studies proved the prognostic benefit of zofenopril vs. placebo or other ACE-inhibitors (ACEIs) in post-acute myocardial infarction (AMI). In this retrospective pooled analysis of these studies we assessed whether the zofenopril effect is influenced by gender.Methodsthe four double-blind, randomized, parallel-group SMILE studies, compared the efficacy and safety of 6–48 week treatment with zofenopril 60 mg/day with that of placebo, lisinopril 10 mg/day or ramipril 10 mg/day in 3630 AMI patients. This pooled analysis compared treatment efficacy (1-year combined occurrence of death or hospitalization for CV causes) in 2733 men and 897 women.Resultswomen were older than men, had a higher prevalence of diabetes and of other major CV risk factors. The risk of a major CV event was significantly larger for women (23% vs. 17% men, p<0.001). Between-gender risk difference was more marked for people living in Southern (+54%) than in Northern Europe (+12%). In both genders zofenopril similarly reduced the 1-year risk of CV morbidity and mortality vs. placebo (−39% men, p = 0.0001; −40% women, p = 0.005). The risk reduction was more marked with zofenopril than with the other ACEIs, particularly in men (−27%, p = 0.012; women: −14%, p = 0.479). The drug safety profile was similar between genders in zofenopril-treated patients, while it was worse in women treated with other ACEIs.Conclusionspost-AMI women are at higher risk of CV complications than men, particularly when living in Mediterranean countries. Their response to ACE-inhibition varies according to the type of drug and is usually better in men.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Effects of Treatment with Zofenopril in Men and Women with Acute Myocardial Infarction: Gender Analysis of the SMILE Program

et al. 2014

View full text Add to dashboard Cite

show abstract

“…When severe, angioedema can lead to airway compromise and death. The mechanism by which ACE inhibitors cause angioedema remains uncertain, but is presumed to relate to impaired degradation of vasoactive peptides that are substrates for ACE, such as bradykinin and substance P. The incidence of ACE inhibitor-associated angioedema has been reported to be from 0.1 to 0.7% in large epidemiological studies to as high as 2.8–6% in randomized- controlled trials of ACE inhibitors [3–5]. The risk of angioedema is increased in African Americans, women, older patients, smokers, individuals with seasonal allergies, and patients taking immunosuppressants [6–9].…”

Section: Introductionmentioning

confidence: 99%

Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema

Paré¹,

Kubo²,

Byrd³

et al. 2013

Pharmacogenetics and Genomics

View full text Add to dashboard Cite

Objective The objective of this study was to identify genetic variants associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. Participants and methods We carried out a genome-wide association study in 175 individuals with ACE inhibitor-associated angioedema and 489 ACE inhibitor-exposed controls from Nashville (Tennessee) and Marshfield (Wisconsin). We tested for replication in 19 cases and 57 controls who participated in Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Results There were no genome-wide significant associations of any single-nucleotide polymorphism (SNP) with angioedema. Sixteen SNPs in African Americans and 41 SNPs in European Americans were associated moderately with angioedema (P<10−4) and evaluated for association in ONTARGET. The T allele of rs500766 in PRKCQ was associated with a reduced risk, whereas the G allele of rs2724635 in ETV6 was associated with an increased risk of ACE inhibitor-associated angioedema in the Nashville/Marshfield sample and ONTARGET. In a candidate gene analysis, rs989692 in the gene encoding neprilysin (MME), an enzyme that degrades bradykinin and substance P, was significantly associated with angioedema in ONTARGET and Nashville/Marshfield African Americans. Conclusion Unlike other serious adverse drug effects, ACE inhibitor-associated angioedema is not associated with a variant with a large effect size. Variants in MME and genes involved in immune regulation may be associated with ACE inhibitor-associated angioedema.

show abstract

“…The reported incidence of ACE inhibitor-associated angioedema varies from 0.1% to 0.7% calculated from postmarketing surveillance or epidemiologic studies, with higher rates reported in some clinical trials (5–7). Risk of ACE inhibitor-associated angioedema is fourfold to fivefold higher in black Americans compared to white Americans (8, 9).…”

mentioning

confidence: 99%

Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use

Byrd

Woodard‐Grice

Stone

et al. 2010

Allergy

View full text Add to dashboard Cite

Background 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. Objective To test the hypothesis that transplant patients are at increased risk of ACE inhibitor-associated angioedema. Methods 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. Results 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. Conclusion Transplant patients are at increased risk of ACE inhibitor-associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.

show abstract

Clinical Profile of Angioedema Associated With Angiotensin Converting-Enzyme Inhibition

Cited by 309 publications

References 18 publications

Effects of Treatment with Zofenopril in Men and Women with Acute Myocardial Infarction: Gender Analysis of the SMILE Program

Effects of Treatment with Zofenopril in Men and Women with Acute Myocardial Infarction: Gender Analysis of the SMILE Program

Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema

Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use

Contact Info

Product

Resources

About