Effects of switching from sacubitril/valsartan to valsartan alone on plasma levels of natriuretic peptides and myocardial remodeling in heart failure with reduced ejection fraction

Background: We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling. Methods: This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 400 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group). The primary endpoint was percent change (%Change) in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels from the baseline to week 24. The secondary endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24. Results: The %Change in ANP and NT-proBNPlevels was significantly greater in the ARB-switch group than that in the ARNI-continue group (ANP, −76.9% vs. −9.1%, P = 0.009; NT-proBNP, 57.9% vs. 17.3%, P = 0.016), whereas the %Change in BNP levels was not significantly different between the two groups ( P = 0.175). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume ( p = 0.043) and LV peak-systolic wall stress ( P = 0.012) from the baseline to week 24 and a trend toward a decrease in LV ejection fraction ( P = 0.080). In the ARNI-continue group, no differences in the echocardiographic parameters were observed from the baseline to week 24. Conclusions: Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels.