PMID- 34521417 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 20 IP - 1 DP - 2021 Sep 14 TI - Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial. PG - 186 LID - 10.1186/s12933-021-01380-w [doi] LID - 186 AB - BACKGROUND: Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. METHODS: Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. RESULTS: The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04). CONCLUSIONS: In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction. CI - (c) 2021. The Author(s). FAU - Kusunose, Kenya AU - Kusunose K AUID- ORCID: 0000-0002-4909-754X AD - Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan. kusunosek@tokushima-u.ac.jp. FAU - Imai, Takumi AU - Imai T AD - Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan. FAU - Tanaka, Atsushi AU - Tanaka A AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. FAU - Dohi, Kaoru AU - Dohi K AD - Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan. FAU - Shiina, Kazuki AU - Shiina K AD - Department of Cardiology, Tokyo Medical University, Tokyo, Japan. FAU - Yamada, Takahisa AU - Yamada T AD - Devision of Cardiology, Osaka General Medical Center, Osaka, Japan. FAU - Kida, Keisuke AU - Kida K AD - Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan. FAU - Eguchi, Kazuo AU - Eguchi K AD - Department of General Internal Medicine, Saitama Red Cross Hospital, Saitama, Japan. FAU - Teragawa, Hiroki AU - Teragawa H AD - Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan. FAU - Takeishi, Yasuchika AU - Takeishi Y AD - Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan. FAU - Ohte, Nobuyuki AU - Ohte N AD - Department of Cardiovascular Medicine, Nagoya City University East Medical Center, Nagoya, Japan. FAU - Yamada, Hirotsugu AU - Yamada H AD - Department of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. FAU - Sata, Masataka AU - Sata M AD - Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan. FAU - Node, Koichi AU - Node K AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. CN - CANDLE Trial Investigators LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210914 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Peptide Fragments) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 0SAC974Z85 (Canagliflozin) RN - 114471-18-0 (Natriuretic Peptide, Brain) SB - IM MH - Aged MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Canagliflozin/adverse effects/*therapeutic use MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy MH - Diastole MH - Female MH - Heart Failure/blood/diagnosis/*drug therapy/physiopathology MH - Humans MH - Japan MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/*blood MH - Peptide Fragments/*blood MH - Prospective Studies MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - Time Factors MH - Treatment Outcome MH - Ventricular Dysfunction, Left/blood/diagnosis/*drug therapy/physiopathology MH - Ventricular Function, Left/*drug effects PMC - PMC8442416 OTO - NOTNLM OT - Canagliflozin OT - Diastolic function OT - Echocardiography OT - NT-proBNP OT - Type 2 diabetes mellitus COIS- TI received honoraria from the Organization for Clinical Medicine Promotion. AT received honoraria from Boehringer Ingelheim and research funding from GlaxoSmithKline. KD received honoraria and a scholarship from Mitsubishi Tanabe Pharma Corporation. KS received grants from Omron Health Care, Asahi Calpis Wellness, Teijin Pharma, and Fukuda Lifetech. K Kida received honorarium from Daiichi Sankyo Co., Novartis Pharmaceuticals Co., Ltd., Otsuka Pharmaceutical Co., Ltd., AstraZeneca K.K., and Ono Pharmaceutical Co., Ltd. HT received honoraria from Abbott Medical Japan, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Ono, Mitsubishi Tanabe, and Takeda. NO received honoraria from Daiichi Sankyo Co, Ltd, and Otsuka Pharmaceutical: scholarship from Daiichi Sankyo Co, Ltd, and Otsuka Pharmaceutical. MS received grants and personal fees from Mitsubishi Tanabe, Takeda, Daiichi Sankyo, Astellas, Pfizer, Novartis, Boehringer Ingelheim, Bayer, MSD, Kowa, and AstraZeneca. SU received grants from Kowa, Bristol-Myers Squibb, Bayer, honoraria from MSD, Boehringer Ingelheim, and Chugai. JO belongs to the endowed department of Fukuda Denshi. KN received research grants from Asahi Kasei, Astellas, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe, Teijin, and Terumo; scholarships from Astellas, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Daiichi Sankyo Healthcare, Takeda, and Teijin; and personal fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo Healthcare, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Novartis, Ono, Takeda, and Teijin. All other authors declare no competing interests. EDAT- 2021/09/16 06:00 MHDA- 2022/02/08 06:00 PMCR- 2021/09/14 CRDT- 2021/09/15 05:45 PHST- 2021/07/30 00:00 [received] PHST- 2021/09/05 00:00 [accepted] PHST- 2021/09/15 05:45 [entrez] PHST- 2021/09/16 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/09/14 00:00 [pmc-release] AID - 10.1186/s12933-021-01380-w [pii] AID - 1380 [pii] AID - 10.1186/s12933-021-01380-w [doi] PST - epublish SO - Cardiovasc Diabetol. 2021 Sep 14;20(1):186. doi: 10.1186/s12933-021-01380-w.