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

Muhammad Shahzeb Khan, Matthew W. Segar, Muhammad Shariq Usman, Kershaw V. Patel, Harriette G.C. Van Spall, Adam D. DeVore, Muthiah Vaduganathan, Carolyn S.P. Lam, Faiez Zannad, Subodh Verma, Javed Butler, W. H.Wilson Tang, Ambarish Pandey

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)825-835
Number of pages11
JournalJACC: Heart Failure
Volume11
Issue number7
DOIs
StatePublished - Jul 2023

Keywords

  • TRS-HF
  • WATCH-DM
  • diabetes
  • heart failure
  • risk scores
  • Heart Failure/drug therapy
  • Canagliflozin/therapeutic use
  • Humans
  • Hospitalization
  • Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
  • Diabetes Mellitus, Type 2/complications

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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