An 84-year-old man comes to the physician with persistent dyspnea despite being treated with optimal medical therapy for congestive heart failure with low left ventricular ejection fraction. A recently published randomized clinical trial compared an angiotensin-neprilysin inhibitor (ANi) to an angiotensin-converting enzyme inhibitor (ACEi) in patients who have heart failure with a reduced ejection fraction. The following results were reported:
Which of the following would be of most concern when switching from an ACEi to an ANi?

Question

An 84-year-old man comes to the physician with persistent dyspnea despite being treated with optimal medical therapy for congestive heart failure with low left ventricular ejection fraction.  A recently published randomized clinical trial compared an angiotensin-neprilysin inhibitor (ANi) to an angiotensin-converting enzyme inhibitor (ACEi) in patients who have heart failure with a reduced ejection fraction.  The following results were reported:
 Which of the following would be of most concern when switching from an ACEi to an ANi?

Quizplus · Accepted Answer

Explanation: Neprilysin is an endopeptidase that degrades natriuretic peptide (B-type natriuretic peptide is elevated in heart failure) and other proteins. Patients randomized to the angiotensin-neprilysin inhibitor (ANi) group had a higher percentage of symptomatic hypotension than those randomized to the angiotensin-converting enzyme inhibitor (ACEi) group (4.1% versus 1.3%), and this difference was statistically significant (P-value <0.001). (Choice A) There was no statistically significant difference in hyperkalemia between the ANi and the ACEi groups (P-value = 0.21). (Choice B) More patients within the ACEi group had >1 hospitalization for a heart failure exacerbation within 90 days of trial initiation. (Choices C and E) The prevalence of cough and renal failure was higher among patients randomized to ACEi; both P-values were statistically significant. Educational objective: Differences that are statistically significant have a P-value <0.05.

An 84-Year-Old Man Comes to the Physician with Persistent Dyspnea