In this episode, I’ll discuss the mechanism of interaction between ACE inhibitors and angiotension II.
Shout out to Academy member JCR for inspiring this episode!
The vasopressor angiotensin II carries a warning in the prescribing information that “ACE inhibitors may increase response to angiotensin II”. No information on why this interaction occurs is provided in the prescribing information.
In general I have found in my practice that warnings without a known rationale or mechanism are more likely to go unheeded by providers, so understanding the mechanism can be essential to avoiding the interaction.
The reason behind this interaction is explained well in a review article published in Pharmacotherapy about the time that Giapreza was approved for use in the US.
The theory is that in the setting of chronic ACE inhibitor use, there is a relatively low level of endogenous angiotensin II, and this causes an upregulation of the AT1 receptor. The AT1 receptor is the same one that angiotensin II activates to provide the vasopressor effect. Therefore it is possible that patients with ACE inhibitor use will have an enhanced response to angiotensin II from upregulation of the AT1 receptor.
A subgroup analysis of patients receiving ACE inhibitors in the ATHOS-3 trial which the FDA used to justify approval of Giapreza did not identify a difference in the outcome, however this subgroup was likely underpowered.
The interaction remains theoretical and does not rise to the level of contraindication.
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