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

Matthew W Segar, Muhammad Shahzeb Khan, 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

Journal: JACC. Heart failure 2023;11(7):825-835

PMID: 37227388

Free Full Text on Elsevier Science View on PubMed

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 [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 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 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 can reliably identify those at high risk for HF hospitalization and most likely to benefit from canagliflozin.

Address: Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Cardiology, Texas Heart Institute, Houston, Texas, USA.; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.; Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas, USA.; Department of Medicine, Population Health Research Institute, Research Institute of St. Joseph's, McMaster University, Hamilton, Ontario, Canada.; Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Durham, North Carolina, USA.; Brigham and Women's Hospital Heart and Vascular Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.; National Heart Centre Singapore, Duke-National University of Singapore, Singapore.; Université de Lorraine, CIC Insert, CHRU, Nancy, France.; Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Ontario, Canada.; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA; Baylor Scott and White Research Institute, Dallas, Texas, USA.; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: [email protected].

DOI: 10.1016/j.jchf.2023.03.025