Angioedema risk not greater among new users of ARNI compared to users of ACE Inhibitors, ARBs

The researchers found an increased risk of angioedema among SV users who recently switched from ACE (angiotensin-converting enzyme) inhibitor or ARB (angiotensin-receptor-blocker) compared with new users sacubitril-valsartan.

In July 2015, sacubitril/valsartan received FDA's approval for use in patients with HFrEF (chronic heart failure with reduced ejection fraction), gaining a broader indication that includes at least some patients with HFpEF (preserved ejection fraction) in February 2021. The approvals were based respectively on findings from the PARADIGM-HF and PARAGON-HF trials.

There is a lack of data on angioedema risk among S.V. users in real-world settings; considering this, Efe Eworuke from the U.S. Food and Drug Administration, Silver Spring, Maryland, USA, and colleagues sought to evaluate angioedema risk among sacubitril-valsartan new users compared with ACE inhibitor and ARB new users separately.

In the study, the researchers compared new users of S.V. (no use of S.V., ARB, or ACE inhibitor six months before) and S.V. new users with prior use (within 183 or 14 days) of ACE inhibitor or ARB (ACE inhibitor–S.V. and ARB-SV users; recent ACE inhibitor–S.V. and current ARB-SV users, respectively) versus ARB and ACE inhibitor new users separately.

The study revealed the following findings:

• Compared with ACE inhibitors, S.V. new (H.R.: 0.18) and ACE inhibitor–S.V. users (H.R.: 0.31) showed a lower risk of angioedema.
• No difference in angioedema risk was seen when S.V. new users (H.R.: 0.59) or ARB-SV users (H.R.: 0.85) were compared with ARB new users.
• Compared with S.V. new users, ACE inhibitor–S.V. users (H.R.: 1.62) trended toward higher angioedema risk, which intensified when the ACE inhibitor to S.V. switch occurred within 14 days (recent ACE inhibitor–S.V.) (H.R.: 1.98).
• ARB-SV users (H.R.: 2.03) experienced an increased risk compared with S.V. new users, which intensified for the more recent switchers (recent ARB-SV) (H.R.: 2.45).

"Among new users of S.V., we did not observe an increased angioedema risk compared with users of ARB or ACE inhibitors," the researchers wrote. "However, there was an increased angioedema risk among S.V. users who recently switched from ACE inhibitor or ARB versus S.V. new users."

Reference:

The study titled "Comparative Risk of Angioedema With Sacubitril-Valsartan vs Renin-Angiotensin-Aldosterone Inhibitors," was published in the Journal of the American College of Cardiology. DOI: https://www.jacc.org/doi/10.1016/j.jacc.2022.10.033