angioedema risk with ace-inhibitors

We recently had an african american male presenting with swollen tongue, lips and a stridor. was intubated for airway compromise..given epinephrine im, benadryl, ranitidine, hydrocortisone. Was extubated the next day after resolution of edema. This gentleman was started on Lisinopril 2 weeks ago for hypertension. This is likely...to be Angioedema due to ace-i!!


The pathophysiologic mechanism of angioedema with regard to ACE inhibitor therapy is believed to relate to the kallikrein-kinin plasma effector system. Bradykinin, which is normally degraded by kininase II/ACE, accumulates in tissues pts on ace-i.  Plasma bradykinin has been shown to increase up to 12-fold during acute angioedema attacks in patients with hereditary or acquired forms of angioedema. A case control study from 1997 showed consistently decreased levels of carboxypeptidase N(kininase1) and C1 esterase inhibitor in pts with angioedema secondary to ace-i Vs pts without angioedema on ace-i.

Another interesting theory has been the association of low levels of dipeptidyl peptidase 4( known to catabolise bradykinin) in pts with ace-i associated angioedema. (Hypertension 2002). The reason this is interesting is because ..... the recent DPP-4 inhibitors(Sitagliptin, Saxagliptin) that we use for diabetes work by inhibiting DPP-4. So if the above theory is true..then we might see an increased risk of angioedema in patients on these medications along with ace-i(as most diabetics need ace-i). Lets wait and see!!!!


Several risk factors for development of angioedema with ace-i have been proposed.The most important predisposing risk factor, evidenced by case-control studies, appears to be ethnic differences.The risk of angioedema with ACE inhibitors is higher in blacks and appears not to be related to dose, specific ACE inhibitors, or concomitant medications...as shown in this nice case control study(Clin Pharm & Ther 1996). Other risk factors are a history of idiopathic angioedema, head and neck surgery, and seafood allergy. 


This study from 1988 ...which looked at 3 studies...each with 12,0000 patients.....showed that the incidence of angioedema is high in the first week of starting Enalapril...and then declined. But previous tolerance to an ACE inhibitor does not exclude the risk for angioedema when therapy is modified to a different ACE inhibitor. Finally...the oberall incidence of angioedema with ace-i is around 0.1 - 0.6% over a period of 6 months (a rough estimate based on studies like OCTAVE  (again showing a higher incidence among African americans than other races)