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 194/206 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 ANP levels in the ARB-switch group significantly decreased (from 1155.7 ± 592.6 pg/mL to 231.6 ± 233.8 pg/mL, p = 0.035), whereas those in the ARNI-continue group were not significant ( p = 0.180). The %Change of decrease in ANP levels was significantly greater in the ARB-switch group than the ARNI-continue group (− 76.9% vs. −9.1%, p = 0.009). BNP levels were not significantly different between the baseline and week 24 in both groups. NT-proBNP levels in the ARB-switch group increased from 1185.3 ± 835.6 pg/mL to 1515.2 ± 1213.5 pg/mL, although the changes were not statistically significant ( p = 0.345). The %Change of increase in NT-proBNP levels was significantly greater in the ARB-switch group than the ARNI-continue group (57.9% vs. 17.3%, p = 0.016). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume (from 41.3 ± 24.1 mL/m 2 to 71.4 ± 8.8 mL/m 2 , p = 0.043) and LV peak-systolic wall stress (from 187.0 ± 42.7 × 10 3 dynes/cm 2 to 279.7 ± 34.1 × 10 3 dynes/cm 2 , 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 echocardiographic parameters were observed from the baseline to week 24. Conclusion Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels.