Rationale and Design of Prospective, Multicenter, Double-Arm Clinical Trial to Investigate the Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus (TOP-HFPEF Trial).

Diastolic function Heart failure with preserved ejection fraction (HFpEF) Sodium–glucose cotransporter 2 (SGLT2) inhibitors Tofogliflozin

Journal

Cardiovascular drugs and therapy
ISSN: 1573-7241
Titre abrégé: Cardiovasc Drugs Ther
Pays: United States
ID NLM: 8712220

Informations de publication

Date de publication:
10 May 2024
Historique:
accepted: 22 04 2024
medline: 10 5 2024
pubmed: 10 5 2024
entrez: 10 5 2024
Statut: aheadofprint

Résumé

Recent large clinical trials have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial. The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20 mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52 weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e' assessed by echocardiography from the baseline to the end of this study (52 weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function. The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus.

Sections du résumé

BACKGROUND BACKGROUND
Recent large clinical trials have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial.
METHODS AND RESULTS RESULTS
The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20 mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52 weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e' assessed by echocardiography from the baseline to the end of this study (52 weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function.
CONCLUSIONS CONCLUSIONS
The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus.

Identifiants

DOI: 10.1007/s10557-024-07576-y PMID: 38727896
pubmed: 38727896
doi: 10.1007/s10557-024-07576-y
pii: 10.1007/s10557-024-07576-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Oren O, Goldberg S. Heart failure with preserved ejection fraction: diagnosis and management. Am J Med. 2017;130(5):510–6. https://doi.org/10.1016/j.amjmed.2016.12.031 .
doi: 10.1016/j.amjmed.2016.12.031 pubmed: 28163048
Nagai T, Yoshikawa T, Saito Y, et al. Clinical characteristics, management, and outcomes of Japanese patients hospitalized for heart failure with preserved ejection fraction - a report from the Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) Registry. Circ J. 2018;82(6):1534–45. https://doi.org/10.1253/circj.CJ-18-0073 .
doi: 10.1253/circj.CJ-18-0073 pubmed: 29576598
Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289(2):194–202. https://doi.org/10.1001/jama.289.2.194 .
doi: 10.1001/jama.289.2.194 pubmed: 12517230
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61. https://doi.org/10.1056/NEJMoa2107038 .
doi: 10.1056/NEJMoa2107038 pubmed: 34449189
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089–98. https://doi.org/10.1056/NEJMoa2206286 .
doi: 10.1056/NEJMoa2206286 pubmed: 36027570
McDonagh TA, Metra M, Adamo M, et al. (2023) Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44:3627–39. https://doi.org/10.1093/eurheartj/ehad195 .
doi: 10.1093/eurheartj/ehad195 pubmed: 37622666
Otagaki M, Matsumura K, Kin H, et al. Effect of tofogliflozin on systolic and diastolic cardiac function in type 2 diabetic patients. Cardiovasc Drugs Ther. 2019;33(4):435–42. https://doi.org/10.1007/s10557-019-06892-y .
doi: 10.1007/s10557-019-06892-y pubmed: 31321581
Lam CS, Roger VL, Rodeheffer RJ, et al. Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County. Minnesota Circulation. 2007;115(15):1982–90. https://doi.org/10.1161/circulationaha.106.659763 .
doi: 10.1161/circulationaha.106.659763 pubmed: 17404159
Dorfs S, Zeh W, Hochholzer W, et al. Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction. Eur Heart J. 2014;35(44):3103–12. https://doi.org/10.1093/eurheartj/ehu315 .
doi: 10.1093/eurheartj/ehu315 pubmed: 25161181
McDonagh TA, Metra M, Adamo M et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. European journal of heart failure. 2022;24(1):4–131. https://doi.org/10.1002/ejhf.2333
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e876–94. https://doi.org/10.1161/cir.0000000000001062 .
doi: 10.1161/cir.0000000000001062 pubmed: 35363500
Okura H, Kubo T, Asawa K, et al. Elevated E/E’ predicts prognosis in congestive heart failure patients with preserved systolic function. Circ J. 2009;73(1):86–91. https://doi.org/10.1253/circj.cj-08-0457 .
doi: 10.1253/circj.cj-08-0457 pubmed: 19015586
Komajda M, Isnard R, Cohen-Solal A, et al. Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial. Eur J Heart Fail. 2017;19(11):1495–503. https://doi.org/10.1002/ejhf.876 .
doi: 10.1002/ejhf.876 pubmed: 28462519
Carubelli V, Zhang Y, Metra M, et al. Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. Eur J Heart Fail. 2020;22(9):1684–93. https://doi.org/10.1002/ejhf.1743 .
doi: 10.1002/ejhf.1743 pubmed: 31975496
Suzuki Y, Kaneko H, Okada A, et al. Comparison of cardiovascular outcomes between SGLT2 inhibitors in diabetes mellitus. Cardiovasc Diabetol. 2022;21(1):67. https://doi.org/10.1186/s12933-022-01508-6 .
doi: 10.1186/s12933-022-01508-6 pubmed: 35585590 pmcid: 9115977
Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020;383(15):1425–35. https://doi.org/10.1056/NEJMoa2004967 .
doi: 10.1056/NEJMoa2004967 pubmed: 32966714
Nikolaou PE, Mylonas N, Makridakis M, et al. Cardioprotection by selective SGLT-2 inhibitors in a non-diabetic mouse model of myocardial ischemia/reperfusion injury: a class or a drug effect? Basic Res Cardiol. 2022;117(1):27. https://doi.org/10.1007/s00395-022-00934-7 .
doi: 10.1007/s00395-022-00934-7 pubmed: 35581445
Shim CY, Seo J, Cho I, et al. Randomized, controlled trial to evaluate the effect of dapagliflozin on left ventricular diastolic function in patients with type 2 diabetes mellitus: the IDDIA trial. Circulation. 2021;143(5):510–2. https://doi.org/10.1161/circulationaha.120.051992 .
doi: 10.1161/circulationaha.120.051992 pubmed: 33186508
Prochaska JH, Jünger C, Schulz A, et al. Effects of empagliflozin on left ventricular diastolic function in addition to usual care in individuals with type 2 diabetes mellitus-results from the randomized, double-blind, placebo-controlled EmDia trial. Clinical research in cardiology : official journal of the German Cardiac Society. 2023;112(7):911–22. https://doi.org/10.1007/s00392-023-02164-w .
doi: 10.1007/s00392-023-02164-w pubmed: 36763159
Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography. 2016;29(4):277–314. https://doi.org/10.1016/j.echo.2016.01.011 .
doi: 10.1016/j.echo.2016.01.011 pubmed: 27037982
Borlaug BA, Reddy YNV, Braun A, et al. Cardiac and metabolic effects of dapagliflozin in heart failure with preserved ejection fraction: the CAMEO-DAPA Trial. Circulation. 2023;148(10):834–44. https://doi.org/10.1161/circulationaha.123.065134 .
doi: 10.1161/circulationaha.123.065134 pubmed: 37534453
Akasaka H, Sugimoto K, Shintani A, et al. Effects of ipragliflozin on left ventricular diastolic function in patients with type 2 diabetes and heart failure with preserved ejection fraction: The EXCEED randomized controlled multicenter study. Geriatr Gerontol Int. 2022;22(4):298–304. https://doi.org/10.1111/ggi.14363 .
doi: 10.1111/ggi.14363 pubmed: 35212104 pmcid: 9305927
Ejiri K, Miyoshi T, Kihara H, et al. Effect of luseogliflozin on heart failure with preserved ejection fraction in patients with diabetes mellitus. J Am Heart Assoc. 2020;9(16): e015103. https://doi.org/10.1161/jaha.119.015103 .
doi: 10.1161/jaha.119.015103 pubmed: 32805185 pmcid: 7660815
Matsutani D, Sakamoto M, Kayama Y, et al. Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17(1):73. https://doi.org/10.1186/s12933-018-0717-9 .
doi: 10.1186/s12933-018-0717-9 pubmed: 29788955 pmcid: 5963148
Yu YW, Zhao XM, Wang YH, et al. Effect of sodium-glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis. Cardiovasc Diabetol. 2021;20(1):25. https://doi.org/10.1186/s12933-020-01209-y .
doi: 10.1186/s12933-020-01209-y pubmed: 33494751 pmcid: 7836497

Auteurs

Shin Ito (S)

Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Suita, Japan.
Department of Heart Failure and Transplant, National Cerebral and Cardiovascular Center, Suita, Japan.

Yuri Nakajima (Y)

Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Suita, Japan.

Hiroki Fukuda (H)

Cardiovascular Center, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan.

Chisato Izumi (C)

Department of Heart Failure and Transplant, National Cerebral and Cardiovascular Center, Suita, Japan.

Gaku Nakazawa (G)

Department of Cardiology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan.

Hajime Yamashita (H)

Department of Cardiology, Baba Memorial Hospital, Sakai, Japan.

Hideo Matsuhisa (H)

Department of Cardiovascular Medicine, Sakai City Medical Center, Sakai, Japan.

Moriaki Inoko (M)

Cardiovascular Center, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan.

Shigeru Toyoda (S)

Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan.

Shin Takiuchi (S)

Department of Cardiology, Higashi Takarazuka Satoh Hospital, Takarazuka, Japan.

Toru Kataoka (T)

Division of Cardiology, Bell Land General Hospital, Sakai, Japan.

Yasuhiro Izumiya (Y)

Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Yukio Abe (Y)

Department of Cardiology, Osaka City General Hospital, Osaka, Japan.

Takashi Sozu (T)

Department of Information and Computer Technology, Faculty of Engineering, Tokyo University of Science, Tokyo, Japan.

Yasushi Sakata (Y)

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Masanori Emoto (M)

Department of Metabolism, Endocrinology and Molecular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Teruo Inoue (T)

Japan Red Cross Society, Nasu Red Cross Hospital, Otawara, Japan.

Masafumi Kitakaze (M)

Hanwa Memorial Hospital, 3-5-8 Minamisumiyoshi, Sumiyoshi-Ku, Osaka, 558-0041, Japan. kitakaze@zf6.so-net.ne.jp.
Non-Profit Organization Think of Medicine in Science, Osaka, Japan. kitakaze@zf6.so-net.ne.jp.
The Osaka Medical Research Foundation for Intractable Diseases, Osaka, Japan. kitakaze@zf6.so-net.ne.jp.
ORCID: 0000-0001-5157-4213

Classifications MeSH