New RAS inhibition with ARNI ‘protective’
Compared with ARNI “new users” who had not received any RAS inhibitor in the prior 6 months, patients in the study who switched from an ACE inhibitor to ARNI (41,548 matched pairs) showed a hazard ratio (HR) for angioedema of 1.62 (95% confidence interval [CI], 0.91-2.89), that is, only a “trend,” the report states.
But that trend became significant when the analysis considered only angioedema cases in the first 14 days after the drug switch: HR, 1.98 (95% CI, 1.11-3.53).
Those switching from an ARB to ARNI, compared with ARNI new users (37,893 matched pairs), showed a significant HR for angioedema of 2.03 (95% CI, 1.16-3.54). The effect was more pronounced when considering only angioedema arising in the first 2 weeks: HR, 2.45 (95% CI, 1.36-4.43).
Compared with new use of ACE inhibitors, new ARNI use (41,998 matched pairs) was “protective,” the report states, with an HR for angioedema of 0.18 (95% CI, 0.11-0.29). So was a switch from ACE inhibitors to the ARNI (69,639 matched pairs), with an HR of 0.31 (95% CI, 0.23-0.43).
But compared with starting with an ARB, ARNI new use (43,755 matched pairs) had a null effect on angioedema risk, HR, 0.59 (95% CI, 0.35-1.01); as did switching from an ARB to ARNI (49,137 matched pairs), HR, 0.85 (95% CI, 0.58-1.26).
The analysis has limitations, Dr. Eworuke acknowledged. The comparator groups probably differed in unknown ways given the limits of propensity matching, for example, and because the FDA’s Sentinel system data can reflect only cases that are reported, the study probably underestimates the true prevalence of angioedema.
For example, a patient may see a clinician for a milder case that resolves without a significant intervention, she noted. But “those types of angioedema would not have been captured by our study.”
Dr. Eworuke disclosed that her comments reflect her views and are not those of the Food and Drug Administration; she and the other authors, as well as editorialist Dr. Page, report no relevant financial relationships.
A version of this article first appeared on Medscape.com.