Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and risk of appendicitis

Abstract Purpose Angiotensin-converting-enzyme (ACE) inhibitors and, less commonly, angiotensin-receptor blockers (ARBs), have been associated with angioedema, including small bowel angioedema. We sought to determine whether this process might be associated with appendicitis. Methods We conducted a nested case-control study of incident appendicitis in a subcohort of 305,958 commercially insured hypertensive adults throughout the United States. Individuals with appendicitis were matched on age, sex, region, and subscriber status with up to 10 controls, and we examined use of ACE inhibitors, ARBs, β-blockers, calcium channel blockers, and thiazides in the previous 12 months. Results A total of 576 cases of appendicitis were matched to 4808 control subjects. The risk of appendicitis appeared greater among users of ACE inhibitors and ARBs (adjusted hazard ratio 1.22; 95% confidence interval 0.98–1.52), but not other antihypertensive classes. Risk was not significantly different between ACE inhibitors and ARBs ( P  = .36). We found a graded increase in risk based upon filled prescriptions, with stepwise greater risk among individuals who filled P trend .03). Conclusions In this population of middle-aged Americans with hypertension, the use of ACE inhibitors or ARBs was associated with greater risk of appendicitis. These results suggest a possible previously unrecognized noncardiovascular side effect of these widespread classes of medication.