Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)
Abstract Aims Little is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.12707 |
| _version_ | 1819178628449042432 |
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| author | Atsushi Tanaka Itaru Hisauchi Isao Taguchi Akira Sezai Shigeru Toyoda Hirofumi Tomiyama Masataka Sata Shinichiro Ueda Jun‐ichi Oyama Masafumi Kitakaze Toyoaki Murohara Koichi Node CANDLE Trial Investigators |
| author_facet | Atsushi Tanaka Itaru Hisauchi Isao Taguchi Akira Sezai Shigeru Toyoda Hirofumi Tomiyama Masataka Sata Shinichiro Ueda Jun‐ichi Oyama Masafumi Kitakaze Toyoaki Murohara Koichi Node CANDLE Trial Investigators |
| author_sort | Atsushi Tanaka |
| collection | DOAJ |
| description | Abstract Aims Little is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in that patient population. Methods and results Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting‐dose: 0.5 mg), were examined using the primary endpoint of non‐inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two‐sided 95% confidence interval (CI) for the group ratio of percentage change in NT‐proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT‐proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non‐inferiority margin. However, NT‐proBNP levels did show a non‐significant trend lower in the canagliflozin group [adjusted group difference; −74.7 pg/mL (95% CI, −159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [−58.3 (95% CI, −127.6 to 11.0, P = 0.098]). Conclusions This study did not meet the predefined primary endpoint of changes in NT‐proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors. |
| first_indexed | 2024-12-22T21:45:34Z |
| format | Article |
| id | doaj.art-04db0cf384aa4091bf15508921787e21 |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-12-22T21:45:34Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-04db0cf384aa4091bf15508921787e212022-12-21T18:11:30ZengWileyESC Heart Failure2055-58222020-08-01741585159410.1002/ehf2.12707Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)Atsushi Tanaka0Itaru Hisauchi1Isao Taguchi2Akira Sezai3Shigeru Toyoda4Hirofumi Tomiyama5Masataka Sata6Shinichiro Ueda7Jun‐ichi Oyama8Masafumi Kitakaze9Toyoaki Murohara10Koichi Node11CANDLE Trial InvestigatorsDepartment of Cardiovascular Medicine Saga University Saga JapanDepartment of Cardiology Dokkyo Medical University Saitama Medical Center Koshigaya JapanDepartment of Cardiology Dokkyo Medical University Saitama Medical Center Koshigaya JapanThe Department of Cardiovascular Surgery Nihon University School of Medicine Tokyo JapanDepartment of Cardiovascular Medicine Dokkyo Medical University School of Medicine Mibu JapanDepartment of Cardiology Tokyo Medical University Tokyo JapanDepartment of Cardiovascular Medicine Tokushima University Graduate School Tokushima JapanDepartment of Clinical Pharmacology and Therapeutics University of the Ryukyus Nishihara JapanDepartment of Cardiovascular Medicine Saga University Saga JapanDepartment of Clinical Medicine and Development National Cerebral and Cardiovascular Center Suita JapanDepartment of Cardiology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Cardiovascular Medicine Saga University Saga JapanAbstract Aims Little is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in that patient population. Methods and results Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting‐dose: 0.5 mg), were examined using the primary endpoint of non‐inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two‐sided 95% confidence interval (CI) for the group ratio of percentage change in NT‐proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT‐proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non‐inferiority margin. However, NT‐proBNP levels did show a non‐significant trend lower in the canagliflozin group [adjusted group difference; −74.7 pg/mL (95% CI, −159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [−58.3 (95% CI, −127.6 to 11.0, P = 0.098]). Conclusions This study did not meet the predefined primary endpoint of changes in NT‐proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors.https://doi.org/10.1002/ehf2.12707Type 2 diabetesHeart failureSGLT2 inhibitorNT‐proBNPNon‐inferiorityGlimepiride |
| spellingShingle | Atsushi Tanaka Itaru Hisauchi Isao Taguchi Akira Sezai Shigeru Toyoda Hirofumi Tomiyama Masataka Sata Shinichiro Ueda Jun‐ichi Oyama Masafumi Kitakaze Toyoaki Murohara Koichi Node CANDLE Trial Investigators Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE) ESC Heart Failure Type 2 diabetes Heart failure SGLT2 inhibitor NT‐proBNP Non‐inferiority Glimepiride |
| title | Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE) |
| title_full | Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE) |
| title_fullStr | Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE) |
| title_full_unstemmed | Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE) |
| title_short | Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE) |
| title_sort | effects of canagliflozin in patients with type 2 diabetes and chronic heart failure a randomized trial candle |
| topic | Type 2 diabetes Heart failure SGLT2 inhibitor NT‐proBNP Non‐inferiority Glimepiride |
| url | https://doi.org/10.1002/ehf2.12707 |
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