Can you give an ARB to a patient with a history of angioedema to ACEIs?
Yes, you can trial one. I actually learned this as an attending on rounds a few years ago - yay lifelong learning - but it came up today and I was discussing it with a colleague and realized how widely practice patterns vary, so figured it was a good topic to explore.
Up To Date says, with respect to drugs affecting bradykinin metabolism, that ARNIs are most consistently a/w angioedema and that we should be careful with direct renin inhibitors and DPP-4 inhibitors as well.
And I want to share two articles with you, because these drugs are so important in our practice.
This one is a meta-analysis of RCTs looking at treatment with ACEIs, ARBs, and direct renin-inhibitors. In the seven trials with head to head comparisons, the risk of ACEI-induced angioedema was 2.2x higher than the risk of ARB-induced angioedema. Importantly, these authors show that the weighted incidence of ACEI-induced angioedema 0.30%, versus 0.11% for ARB-induced angioedema and 0.07% for placebo, leading them to draw the conclusion that the incidence of angioedema is not significantly different between ARBs and placebo. I found this picture helpful:
Figure 2. Weighted incidence of angioedema for renin-angiotensin system inhibitors and their comparators
And this one:
Figure 4. Head-to head comparison of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers to placebo on risk of angioedema
And then the other paper I read is the one I'm attaching here because although the population has less external validity, the approach to the question is more aligned. This group in Denmark identified patients with a history of angioedema to an ACEI and then used propensity scores to adjust hazard ratios for risk of recurrent angioedema. Here are their results:
Table 3. Crude and propensity score adjusted hazard ratios (with 95% CIs) for the use of different antihypertensives relative to the development of angioedema are shown
And I liked this table:
Table 2. Follow-up for each drug category, number of angioedema episodes and crude incidence rates of angioedema during treatment
There are definitely limitations which are noted: proper diagnosis of angioedema, mild cases not being included, confounding medications. But, I appreciated the history and explanation in this discussion section, and based on all this data, I do feel comfortable trialing an ARB after ACEI-induced angioedema for patients with proper counseling.
Makani H, Messerli FH, Romero J, et al. Meta-Analysis of Randomized Trials of Angioedema as an Adverse Event of Renin–Angiotensin System Inhibitors. The American Journal of Cardiology. 2012;110(3):383-391. doi:https://doi.org/10.1016/j.amjcard.2012.03.034
Rasmussen ER, Pottegård A, Bygum A, von Buchwald C, Homøe P, Hallas J. Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study. Journal of Internal Medicine. 2019;285(5):553-561. doi:https://doi.org/10.1111/joim.12867
