James L Januzzi1, Jialin Xu2, JingWei Li3, Wayne Shaw4, Richard Oh4, Michael Pfeifer5, Javed Butler6, Naveed Sattar7, Kenneth W Mahaffey8, Bruce Neal9, Michael K Hansen2. 1. Massachusetts General Hospital and Baim Institute for Clinical Research, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org. 2. Janssen Research & Development, LLC, Spring House, Pennsylvania. 3. Department of Cardiology, Xinqiao Hospital, Army Military Medical University, Chongqing, China; Department of Cardiology, People's Liberation Army General Hospital, Beijing, China; The George Institute for Global Health, UNSW Sydney, Sydney, Australia. 4. Janssen Research & Development, LLC, Raritan, New Jersey. 5. Janssen Scientific Affairs, LLC, Titusville, New Jersey. 6. Department of Medicine, University of Mississippi, Jackson, Missouri. 7. Glasgow Cardiovascular Research, Glasgow, United Kingdom. 8. Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California. 9. The George Institute for Global Health, UNSW Sydney, Sydney, Australia; Charles Perkins Centre, University of Sydney, Sydney, Australia; Imperial College London, London, United Kingdom.
Abstract
BACKGROUND:Canagliflozin reduces cardiovascular events including hospitalization for heart failure (HHF) in patients with type 2 diabetes and cardiovascular risk. Elevated amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with HF diagnosis and predict cardiovascular risk. OBJECTIVES: The purpose of this study was to measure NT-proBNP in CANVAS (Canagliflozin Cardiovascular Assessment Study) participants. METHODS: Associations between baseline NT-proBNP and cardiovascular, renal, and mortality outcomes and intervention-associated changes were determined. RESULTS: Of the 4,330 participants in the CANVAS trial, NT-proBNP was measured in 3,587, 2,918, and 995 participants at baseline, 1 year, and 6 years, respectively. The median baseline NT-proBNP concentration was 91 pg/ml, and 39.3% had NT-proBNP ≥125 pg/ml. NT-proBNP was higher in those with investigator-reported HF (13% of participants at baseline) versus those without (187 pg/ml vs. 81 pg/ml), with substantial overlap between groups. By 1 year, NT-proBNP increased with placebo, whereas canagliflozin reduced NT-proBNP by 11% (geometric mean ratio for canagliflozin vs. placebo = 0.89 [95% confidence interval (CI): 0.84 to 0.94]; p < 0.001). Lower NT-proBNP with canagliflozin was also observed at 6 years (p = 0.004). In adjusted models, baseline NT-proBNP ≥125 pg/ml was prognostic for incident HHF (hazard ratio [HR]: 5.40; 95% CI: 2.67 to 10.9), HHF/cardiovascular death (HR: 3.52; 95% CI: 2.38 to 5.20), and all-cause death (HR: 2.53; 95% CI: 1.78 to 3.61). Mediation analyses suggested that 10.4% of the effects of canagliflozin on HHF were reflected in NT-proBNP lowering. CONCLUSIONS: A substantial percentage of patients in the CANVAS trial had elevated NT-proBNP values. Canagliflozin reduced NT-proBNP concentrations versus placebo; however, reduction in NT-proBNP explained only a small proportion of the benefit of canagliflozin on HF events. (CANVAS [CANagliflozin cardioVascular Assessment Study]; NCT01032629).
RCT Entities:
BACKGROUND:Canagliflozin reduces cardiovascular events including hospitalization for heart failure (HHF) in patients with type 2 diabetes and cardiovascular risk. Elevated amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with HF diagnosis and predict cardiovascular risk. OBJECTIVES: The purpose of this study was to measure NT-proBNP in CANVAS (CanagliflozinCardiovascular Assessment Study) participants. METHODS: Associations between baseline NT-proBNP and cardiovascular, renal, and mortality outcomes and intervention-associated changes were determined. RESULTS: Of the 4,330 participants in the CANVAS trial, NT-proBNP was measured in 3,587, 2,918, and 995 participants at baseline, 1 year, and 6 years, respectively. The median baseline NT-proBNP concentration was 91 pg/ml, and 39.3% had NT-proBNP ≥125 pg/ml. NT-proBNP was higher in those with investigator-reported HF (13% of participants at baseline) versus those without (187 pg/ml vs. 81 pg/ml), with substantial overlap between groups. By 1 year, NT-proBNP increased with placebo, whereas canagliflozin reduced NT-proBNP by 11% (geometric mean ratio for canagliflozin vs. placebo = 0.89 [95% confidence interval (CI): 0.84 to 0.94]; p < 0.001). Lower NT-proBNP with canagliflozin was also observed at 6 years (p = 0.004). In adjusted models, baseline NT-proBNP ≥125 pg/ml was prognostic for incident HHF (hazard ratio [HR]: 5.40; 95% CI: 2.67 to 10.9), HHF/cardiovascular death (HR: 3.52; 95% CI: 2.38 to 5.20), and all-cause death (HR: 2.53; 95% CI: 1.78 to 3.61). Mediation analyses suggested that 10.4% of the effects of canagliflozin on HHF were reflected in NT-proBNP lowering. CONCLUSIONS: A substantial percentage of patients in the CANVAS trial had elevated NT-proBNP values. Canagliflozin reduced NT-proBNP concentrations versus placebo; however, reduction in NT-proBNP explained only a small proportion of the benefit of canagliflozin on HF events. (CANVAS [CANagliflozincardioVascular Assessment Study]; NCT01032629).
Authors: Archana Rai; Kim A Connelly; Subodh Verma; C David Mazer; Hwee Teoh; Ming-Yen Ng; Idan Roifman; Adrian Quan; Marina Pourafkari; Laura Jimenez-Juan; Venkat Ramanan; Yin Ge; Djeven P Deva; Andrew T Yan Journal: Acta Diabetol Date: 2022-01-21 Impact factor: 4.280
Authors: Suriya Prausmüller; Michael Resl; Henrike Arfsten; Georg Spinka; Raphael Wurm; Stephanie Neuhold; Philipp E Bartko; Georg Goliasch; Guido Strunk; Noemi Pavo; Martin Clodi; Martin Hülsmann Journal: Cardiovasc Diabetol Date: 2021-02-02 Impact factor: 9.951