Use of canagliflozin leads to a decrease in amino-terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations as compared with placebo, but the reduction in NT-proBNP explains only a small part of the benefit of this agent on heart failure (HF) events, suggests a recent study.
The investigators sought to determine the associations between baseline NT-proBNP and cardiovascular, renal, and mortality outcomes, as well as intervention-related changes among participants of the Canagliflozin Cardiovascular Assessment Study (CANVAS).
A total of 4,330 participants were included in CANVAS, of whom 3,587 had their NT-proBNP measured at baseline, 2,918 at 1 year, and 995 at 6 years. The median baseline NT-proBNP concentration was 91 pg/ml; 39.3 percent had NT-proBNP ≥125 pg/ml.
Participants with investigator-reported HF (13 percent) had higher NT-proBNP than those without (187 vs 81 pg/ml), with substantial overlap between groups. By 1 year, NT-proBNP increased with placebo but decreased with canagliflozin by 11 percent (geometric mean ratio, 0.89, 95 percent confidence interval [CI], 0.84–0.94; p<0.001). At 6 years, NT-proBNP was lower with canagliflozin (p=0.004).
Baseline NT-proBNP ≥125 pg/ml was prognostic for incident hospitalization for HF (HHF; hazard ratio [HR], 5.40, 95 percent CI, 2.67–10.9), HHF/cardiovascular death (HR, 3.52, 95 percent CI, 2.38–5.20), and all-cause mortality (HR, 2.53, 95 percent CI, 1.78–3.61) in adjusted models. In mediation analyses, 10.4 percent of the effects of canagliflozin on HHF were attributed to NT-proBNP reduction.
“Canagliflozin reduces cardiovascular events including hospitalization for HF in patients with type 2 diabetes and cardiovascular risk,” the investigators said. “Elevated NT-proBNP concentrations are associated with HF diagnosis and predict cardiovascular risk.”
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