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Multi-marker biomarker panel, adverse cardiovascular and kidney outcomes, and response to canagliflozin in the CANVAS Program

2021 European Society of Cardiology ;ISSN: 1388-9842 ;EISSN: 1879-0844 ;DOI: 10.1002/ejhf.2297

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  • Title:
    Multi-marker biomarker panel, adverse cardiovascular and kidney outcomes, and response to canagliflozin in the CANVAS Program
  • Author: Vaduganathan, M ; Sattar, N ; Xu, J ; Butler, J ; Mahaffey, KW ; Neal, B ; Shaw, W ; Rosenthal, N ; Pfeifer, M ; Hansen, MK ; Januzzi, JL
  • Subjects: 1102 Cardiorespiratory Medicine and Haematology ; Cardiac & Cardiovascular Systems ; Cardiovascular System & Cardiology ; Cardiovascular System & Hematology ; Life Sciences & Biomedicine ; Science & Technology
  • Description: Background/Introduction: Circulating biomarkers reflecting different mechanistic pathways may identify patients most likely to benefit from sodium glucose co-transporter 2 (SGLT2) inhibitors. Purpose: To determine if 3 biomarkers (high sensitivity cardiac troponin T [hs-cTnT], soluble ST2 [sST2], and insulin-like growth factor binding protein 7 [IGFBP7]) have prognostic implications or modify treatment response to canagliflozin in the CANVAS trial. Methods: Among 3,040 participants in the CANVAS trial with available biomarker data, we created a multi-marker panel assigning 1 point for each abnormally elevated level of hs-cTnT, sST2, and IGFBP7. We assessed its association with risk of cardiac and kidney outcomes, and whether each biomarker alone or as a multi-marker panel modified the treatment response to canagliflozin. Incremental discrimination was tested by comparing C-statistics of a base clinical model plus each individual biomarker (or multi-marker panel) vs. the base clinical model alone (age, eGFR, body mass index, systolic blood pressure, HbA1c, duration of diabetes, urine albumin:creatinine ratio, history of HF, and diuretic use). Results: Among placebo-treated participants, 38% had elevated levels of hs-cTnT ≥14 pg/mL, 7% had sST2 >35 ng/mL, and 49% had IGFBP7 >96.5ng/mL. Overall, 1,102 (36%), 1,051 (35%), 819 (27%), and 68 (2%) had 0, 1, 2, and 3 elevated biomarkers. Increasing numbers of elevated biomarkers independently predicted each cardiac and kidney outcome in a graded fashion and improved risk discrimination compared with clinical variables alone (C-statistic improvement by +0.04 to +0.06) (Figure). Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentrations, however patients with elevated hs-cTnT appeared to derive greater relative benefit for major adverse cardiovascular events (MACE) compared with those with lower values (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.61-0.97 vs. HR 1.10; 95% CI 0.83-1.44; Pinteraction=0.05). Similarly, patients with elevated IGFBP7 >96.5 ng/mL (HR 0.81; 95% CI 0.64-1.01) appeared to derive greater relative treatment effects for stroke compared with patients with normal IGFBP7 ≤96.5 ng/mL (HR 1.03; 95% CI 0.78-1.36; Pinteraction=0.05). Participants with an increasing number of abnormal circulating biomarkers appeared to have greatest relative reductions in MACE from canagliflozin treatment: 0 abnormal biomarkers (HR 0.94; 95% CI 0.63-1.39), 1 abnormal biomarker (HR 1.36; 95% CI 0.96-1.92), 2 abnormal biomarkers (HR 0.62; 95% CI 0.46-0.83), and 3 abnormal biomarkers (HR 0.44; 95% CI 0.19-1.01); Pinteraction trend=0.009. Conclusions: Circulating markers of myocardial injury and remodeling are frequently abnormal in patients with type 2 diabetes at high cardiovascular risk and may identify patients who may derive greater benefit from SGLT2 inhibitors.
  • Publisher: WILEY
  • Creation Date: 2021
  • Language: English
  • Identifier: ISSN: 1388-9842
    EISSN: 1879-0844
    DOI: 10.1002/ejhf.2297
  • Source: Spiral
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