Abstract 14752: FGF-23, Cardiovascular Events, and the Benefit of Canagliflozin in the CANVAS Trial

Background: The incremental prognostic value of FGF-23 with cardiovascular (CV) risk, composite kidney outcomes (KO) and treatment response was assessed in the CANVAS trial, which studied the efficacy of the sodium glucose co-transporter 2 inhibitor canagliflozin (cana) versus placebo in patients with type 2 diabetes (T2D) and high CV risk.

Methods: 3188 patients with available baseline FGF-23 samples were studied. The association between FGF-23 and the composite of time to CV death or hospitalization for heart failure (HHF) (primary endpoint), HHF, CV death, major adverse CV events (MACE) and KO were assessed using multivariable Cox proportional hazard regression models adjusted for clinical risk factors. Events rates by randomized treatment assignment were calculated for FGF-23 after assignment to a ‘low risk’ (Quartiles 1-3) or ‘high risk’ (Q4) group.

Results: The median level of FGF-23 was 64.1 RU/mL (IQR 48.3-94.1). A doubling of FGF-23 was significantly associated with the primary endpoint (HR, 1.32; 95% CI, 1.19-1.46; P <0.001) as well as HHF (HR, 1.53; 95% CI, 1.31-1.79, P <0.001), CV death (HR, 1.18; 95% CI, 1.03-1.35, P =0.014), and KO (HR, 1.11; 95% CI, 1.02-1.21, P =0.014) but not MACE (HR, 1.05; 0.95-1.15, P =0.3) in the fully adjusted model (Table 1). Cana yielded consistent risk reduction for the primary endpoint, HHF and KO regardless of whether patients were categorized in the high or low risk group (all P heterogeneity>0.30) (Table 2).

Conclusion: High levels of FGF-23 are associated with an increased risk of CV death and HHF, HHF, CV death, and KO in patients with T2D and high CV risk. Treatment with cana provides consistent benefit across higher and lower levels of FGF-23.