Examination of baseline levels of carboxypeptidase N and complement components as potential predictors of angioedema associated with the use of an angiotensin-converting enzyme inhibitor.
OBJECTIVE
To determine if mean levels of complement components and carboxypeptidase N differed when comparing patients who exhibited angioedema following angiotensin-converting enzyme inhibitor therapy to those who received angiotensin-converting enzyme inhibitor therapy but did not have angioedema.


METHODS
Case-control study nested within an 8-week, open-label study of the use of quinapril hydrochloride for hypertension in 12275 patients.


METHODS
Multicenter, with sites throughout the United States.


METHODS
Of the 36 patients with angioedema described, 22 participated in the study. They were matched to 48 controls by age, sex, race, length of follow-up, and geographical region.


METHODS
All patients received quinapril therapy prior to participation in this case-control study.


METHODS
Levels of carboxypeptidase N, total hemolytic complement, C1 esterase inhibitor, and C4, along with questionnaire data, including a history of angioedema-like episodes and family history of angioedema.


RESULTS
The 22 patients had significantly lower mean levels of carboxypeptidase N (kininase I) (P = .03) and C1 esterase inhibitor (P = .04) compared with the 48 matched controls, but all mean values were within normal laboratory ranges. A history of prior angioedema-like episodes was associated with an approximate 6-fold increase in the subsequent risk of angioedema following angiotensin-converting enzyme inhibitor therapy.


CONCLUSIONS
Small differences in levels of carboxypeptidase N or C1 esterase inhibitor may contribute to an increased risk of angioedema with angiotensin-converting enzyme inhibitor therapy. Given the large overlap in the distributions of carboxypeptidase N and C1 esterase inhibitor levels, prior testing could not be used to evaluate angioedema risk for an individual patient considering angiotensin-converting enzyme inhibitor therapy. A history of prior angioedema-like episodes was associated with increased risk, but this result should be interpreted with caution because of possible recall bias.
Sigler
C
C
Safety and Epidemiology Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Mich., USA.
Annis
K
K
Cooper
K
K
Haber
H
H
Van deCarr
S
S
D000799:Angioedema / Q000097:blood* / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use*; D001121:Lysine Carboxypeptidase / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D000077583:Quinapril; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D003165:Complement System Proteins; D001121:Lysine Carboxypeptidase; D000077583:Quinapril