PMID- 36942494 OWN - NLM STAT- MEDLINE DCOM- 20230520 LR - 20230526 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 10 IP - 3 DP - 2023 Jun TI - Effects of angiotensin receptor-neprilysin inhibitor on insulin resistance in patients with heart failure. PG - 1860-1870 LID - 10.1002/ehf2.14352 [doi] AB - 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) muU/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) muU/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. CI - (c) 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. FAU - Kashiwagi, Yusuke AU - Kashiwagi Y AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Nagoshi, Tomohisa AU - Nagoshi T AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Kimura, Haruka AU - Kimura H AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Tanaka, Yoshiro AU - Tanaka Y AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Oi, Yuhei AU - Oi Y AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Inoue, Yasunori AU - Inoue Y AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Ogawa, Kazuo AU - Ogawa K AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Kawai, Makoto AU - Kawai M AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Yoshimura, Michihiro AU - Yoshimura M AD - Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20230321 PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Antihypertensive Agents) RN - IY9XDZ35W2 (Glucose) RN - 0 (Insulins) RN - EC 3.4.24.11 (Neprilysin) RN - 268B43MJ25 (Uric Acid) SB - IM MH - Humans MH - Angiotensin Receptor Antagonists/therapeutic use/pharmacology MH - Angiotensin-Converting Enzyme Inhibitors/pharmacology MH - Antihypertensive Agents MH - Glucose MH - *Heart Failure/drug therapy MH - *Insulin Resistance MH - *Insulins MH - Neprilysin MH - Retrospective Studies MH - Stroke Volume MH - Treatment Outcome MH - Uric Acid MH - *Ventricular Dysfunction, Left PMC - PMC10192229 OTO - NOTNLM OT - Angiotensin receptor-neprilysin inhibitor OT - Heart failure OT - Insulin resistance OT - Structural equation model analysis OT - Uric acid COIS- There are no conflicts of interest to disclose directly related to this study. Outside this study, Michihiro Yoshimura received research funds from Teijin Pharma Ltd., Shionogi & Co. Ltd., Otsuka Pharmaceutical Co. Ltd., and Mochida Pharmaceutical Co. Ltd., and speaker's honorarium from Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., AstraZeneca K.K., Otsuka Pharmaceutical Co. Ltd, Astellas Pharma Inc., Bayer Yakuhin Ltd., Novartis Pharma K.K., and Mochida Pharmaceutical Co., Ltd. EDAT- 2023/03/22 06:00 MHDA- 2023/05/19 06:42 PMCR- 2023/03/21 CRDT- 2023/03/21 04:12 PHST- 2023/01/20 00:00 [revised] PHST- 2022/10/13 00:00 [received] PHST- 2023/02/27 00:00 [accepted] PHST- 2023/05/19 06:42 [medline] PHST- 2023/03/22 06:00 [pubmed] PHST- 2023/03/21 04:12 [entrez] PHST- 2023/03/21 00:00 [pmc-release] AID - EHF214352 [pii] AID - 10.1002/ehf2.14352 [doi] PST - ppublish SO - ESC Heart Fail. 2023 Jun;10(3):1860-1870. doi: 10.1002/ehf2.14352. Epub 2023 Mar 21.