SGLT2 inhibitors reduce risk of major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF) in patients with type 2 diabetes (T2D), but mechanisms remain unclear. We examined effects of canagliflozin vs. placebo on 3 prognostic biomarkers in CANVAS, as well as their predictive ability for outcomes of interest.
High sensitivity cardiac troponin T (hs-cTnT; Roche Diagnostics), soluble (s)ST2 (Critical Diagnostics), and insulin-like growth factor binding protein 7 (IGFBP7; Roche Diagnostics) were measured in up to 3680 participants at baseline, 1 y, and for hs-cTnT and sST2, 6 y. Conventional statistical methods adjusting relevant covariates were used to relate biomarkers to risk for incident MACE or HHF.
Higher concentration of all 3 biomarkers was associated with higher adjusted risk for incident MACE or HHF, with C-index improvements beyond covariates for MACE or HHF (Table). In terms of treatment effect, no biomarkers were differentially altered by 1 y but where data existed, both hs-cTnT (n=915; treatment coefficient [95% CI]: -0.064 [-0.121, -0.007]; p=0.027) and sST2 (n=828, treatment coefficient [95% CI]: -0.129 [-0.248, -0.010]; p=0.033) were reduced significantly at 6 y.
Among patients with T2D, concentrations of hs-cTnT, sST2, and IGFBP7 were associated with risk for MACE and HHF. Canagliflozin slowed longer term (6 y) increases in hs-cTnT and sST2.
N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Xu: Employee; Self; Janssen Research & Development, LLC. J. Butler: Consultant; Self; Amgen, Array BioPharma, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife Co., Ltd., Janssen Pharmaceuticals, Inc., Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Relypsa, Inc., VIfor. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. W. Shaw: Employee; Self; Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.E. Gutstein: Employee; Self; Janssen Research & Development, LLC. M.K. Hansen: Employee; Self; Janssen Research & Development, LLC. J. Januzzi: Consultant; Self; Roche Diagnostic USA. Research Support; Self; Janssen Pharmaceuticals, Inc.
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