Effect of Canagliflozin on Heart Failure Hospitalization in Diabetes According to Baseline Heart Failure Risk.

Background: In the CANVAS (Canagliflozin Cardiovascular Assessment Study) program, canagliflozin reduced the risk of heart failure (HF) hospitalization among individuals with type 2 diabetes mellitus (T2DM).
Objectives: The purpose of this study was to evaluate heterogeneity in absolute and relative treatment effects of canagliflozin on HF hospitalization according to baseline HF risk as assessed by diabetes-specific HF risk scores (WATCH-DM [Weight (body mass index), Age, hyperTension, Creatinine, HDL-C, Diabetes control (fasting plasma glucose) and QRS Duration, MI and CABG] and TRS-HF _DM [TIMI Risk Score for HF in Diabetes]).
Methods: Participants in the CANVAS trial were categorized into low, medium, and high risk for HF using the WATCH-DM score (for participants without prevalent HF) and the TRS-HF _DM score (for all participants). The outcome of interest was time to first HF hospitalization. The treatment effect of canagliflozin vs placebo for HF hospitalization was compared across risk strata.
Results: Among 10,137 participants with available HF data, 1,446 (14.3%) had HF at baseline. Among participants without baseline HF, WATCH-DM risk category did not modify the treatment effect of canagliflozin (vs placebo) on HF hospitalization (P interaction = 0.56). However, the absolute and relative risk reduction with canagliflozin was numerically greater in the high-risk group (cumulative incidence, canagliflozin vs placebo: 8.1% vs 12.7%; HR: 0.62 [95% CI: 0.37-0.93]; P = 0.03; number needed to treat: 22) than in the low- and intermediate-risk groups. When overall study participants were categorized according to the TRS-HF _DM score, a statistically significant difference in the treatment effect of canagliflozin across risk strata was observed (P interaction = 0.04). Canagliflozin significantly reduced the risk of HF hospitalization by 39% in the high-risk group (HR: 0.61 [95% CI: 0.48-0.78]; P < 0.001; number needed to treat: 20) but not in the intermediate- or low-risk groups.
Conclusions: Among participants with T2DM, the WATCH-DM and TRS-HF _DM can reliably identify those at high risk for HF hospitalization and most likely to benefit from canagliflozin.
Competing Interests: Funding Support and Author Disclosures This study, carried out under YODA Project # 2020-4213, used data obtained from the Yale University Open Data Access Project, which has an agreement with Janssen Research and Development, LLC. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or Janssen Research and Development, LLC. Dr Khan has received personal fees from Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr DeVore has received research funding through his institution from the American Heart Association, Biofourmis, Bodyport, Cytokinetics, American Regent Inc, the National Heart, Lung, and Blood Institute, Novartis, and Story Health; has provided consulting services for and/or received honoraria from Abiomed, AstraZeneca, Cardionomic, InnaMed, LivaNova, Natera, Novartis, Procyrion, Story Health, Vifor, and Zoll; and has received nonfinancial support from Abbott for educational and research activities. Dr Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health/National Center for Advancing Translational Sciences Award UL 1TR002541); and has served on advisory boards or has received research grant support from American Regent, Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr Lam has received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics; has served as a consultant or on advisory boards/steering committees/executive committees for Actelion, Alleviant Medical, Allysta, Amgen, ANaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma, EchoNous, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research and Development, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, Us2.ai and WebMD Global; and has served as cofounder and non-executive director of Us2.ai. Dr Zannad has received personal fees from Boehringer Ingelheim during the conduct of the study; has received personal fees from Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and Cellprothera outside of the submitted work; and has received other support from cardiovascular clinical trialists and Cardiorenal outside of the submitted work. Dr Verma holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; has received research grants and honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, PhaseBio, and Pfizer; has received honoraria from Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; is a member of the scientific excellence committee of the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure With Reduced Ejection Fraction); has served as a national lead investigator of the DAPA-HF and EMPEROR-Reduced trials; and is the president of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. Dr Butler has received consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd, and Vifor. Dr Pandey has received grant funding outside the present study from Applied Therapeutics; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly, USA, Rivus, and Roche Diagnostics; has received nonfinancial support from Pfizer and Merck; is supported by the Texas Health Resources Clinical Scholarship, Gilead Sciences Research Scholar Program, and the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01); and has received grant support from Applied Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)