Effects of angiotensin receptor‐neprilysin inhibitor on insulin resistance in patients with heart failure

Abstract

Aims Although the haemodynamic effects of angiotensin receptor‐neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis. Methods We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group). Results At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) μU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA‐IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA‐IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) μU/mL, P < 0.001; HOMA‐IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA‐IR levels at 3 months independently of the baseline fasting blood insulin and HOMA‐IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008). Conclusions In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.

Effects of angiotensin receptor-neprilysin inhibitor on ketone body metabolism in pre-heart failure/heart failure patients

“…Previous studies have reported that treatment with ARNI resulted in improved glucose metabolism 18 , 19 . We also found that ARNI administration improved insulin resistance in patients with stable chronic heart failure 20 . However, the mechanism by which ARNI affects ketone body metabolism is not yet fully understood.…”

“…ARNI treatment was initially started at 100 or 200 mg/day by carefully monitoring the blood pressure and other clinical parameters. For all patients in the present study, no other medications were added or changed from four weeks prior to screening to the end of the observation period, as previously described 20 .…”

“…Instead of obtaining informed consent from each patient, we posted a notice about the study design and contact information at a public location in our institution, according to our routine ethical regulations. In this public notification, we ensured that patients had the opportunity to refuse to participate (opt-out) in the study, as previously described 20 .…”

“…Data are expressed as the mean ± standard error (SE) or as the median (25th, 75th percentile) for significantly skewed variables. For continuous variables, differences between two groups were evaluated using either an unpaired Student’s t -test or the Mann–Whitney rank-sum test, and differences within groups were evaluated using a paired t -test or Wilcoxon’s signed-rank test, as previously described 20 . For discrete variables, which were expressed as counts and percentages, differences between the two groups were analyzed using the chi-square test, unless the expected value in any cell was < 5, in which case Fisher’s exact test was used.…”