Patients with ACE Inhibitor-induced Swelling May Safely Switch to AT2 Blockers, Study Suggests

Patients who experience an angioedema attack during treatment with angiotensin-converting enzyme inhibitors — a kind of medication for high blood pressure and heart failure — may safely switch to a different kind of blood pressure medication called angiotensin II receptor blockers, a study found.

The study, “Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin‐converting enzyme inhibitors – a nationwide registry‐based cohort study,” was published in the Journal of Internal Medicine.

While angiotensin-converting enzyme (ACE) inhibitors are widely used to treat high blood pressure, nearly 30% of patients do not tolerate them well. In some cases, angioedema (swelling) attacks may occur. This swelling happens because ACE inhibition releases metabolites of bradykinin, an inflammatory molecule that acts as a potent dilator of certain blood vessels, causing fluid to build up inside tissues. In most cases, swelling occurs in the upper airways, which can lead to a life-threatening risk of suffocation.

When patients discontinue ACE inhibitors, they usually need treatment with another blood pressure medication. In cases with angioedema, angiotensin II receptor (AT2) blockers could be a potential replacement, as they do not interfere with bradykinin metabolism.

However, while a few studies have addressed the issue, it is presumed that AT2 blockers increase the risk of a second attack in patients who discontinued ACE inhibitors due to angioedema. To find out if this was the case, researchers in Denmark conducted a retrospective study examining patients who received a second blood pressure medicine after experiencing angioedema during treatment with ACE inhibitors. The study’s primary goal was to determine if AT2 blockers could be given safely to these patients. A secondary goal was to investigate if the risk for angioedema was higher with AT2 blockers than with any other blood pressure medicine or no treatment.

The researchers examined 1,106,024 users of ACE inhibitors among three Danish health registries — the Danish National Patient Registry, the Danish National Prescription Registry, and the Danish Civil Registration System. Of these, 5,507 experienced an angioedema attack during treatment, representing an incidence rate of 0.5%.

Patients treated with AT2 blockers had a 61% lower risk of having more angioedema attacks than those given any other high blood pressure medications, the researchers found.

The risk of recurrent angioedema was the highest for patients who used ACE inhibitors after their first swelling attacks — 45% higher than the other participants. Other high blood pressure medications had no impact on angioedema risk.

The benefits of AT2 blockers were particularly higher for female patients, those 65 or older, and patients diagnosed with diabetes or congestive heart failure.

This “should not be interpreted as an indication that AT2s generally protect against angioedema,” the researchers said. “One factor contributing to the inverse association could be that physicians are more cautious when using an AT2 to treat patients who have experienced angioedema during ACEi (ACE inhibitor) treatment.”

“AT2s can safely replace ACEi in patients who experience angioedema during ACEi treatment. We observed a moderate inverse association between AT2s and angioedema in our selected population. The underlying explanation for this is unknown and a potential focus for future studies,” they concluded.