Canagliflozin was found to lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in patients with type 2 diabetes (T2DM) who are at risk for cardiovascular (CV) disease, according to a study published in the Journal of the American College of Cardiology.
Elevated NT-proBNP levels (≥125 pg/mL) are associated with CV risk and heart failure (HF) diagnosis. Canagliflozin was found to reduce CV events, including rates of hospitalization for HF in patients with T2DM.
In this secondary analysis of the data of 3587 participants (mean age, 62.7 years; 67% men; 81% White) from the Canagliflozin Cardiovascular Assessment Study (CANVAS; ClinicalTrials.gov Identifier: NCT01032629), investigators sought to examine associations between NT-proBNP baseline levels and changes in these levels over time with CV and renal outcomes, as well as mortality rates. In the CANVAS trial, participants were randomly assigned 1:1:1 to receive canagliflozin at 100 mg or 300 mg daily, or placebo. In this sub-analysis, the 2 canagliflozin groups were combined (n=2390; mean age, 62.8 years) and compared with the placebo group (n=1197; mean age, 62.5 years).
Plasma concentrations of NT-proBNP were measured at baseline (n=3587), 1 year (n=2918), and 6 years (n=995), with a median follow-up duration of 5.75 years. At baseline, the median NT-proBNP level was 91 pg/mL, with 39.3% of participants with levels ≥125 pg/mL. In addition, 13% of patients had investigator-reported HF at the beginning of the study. Participants with vs without HF at baseline had higher mean NT-proBNP baseline levels (187 pg/mL vs 81 pg/mL, respectively).
After 1 year, the mean NT-proBNP levels increased in the placebo group, and decreased by 11% in the canagliflozin group (geometric mean ratio, 0.889; 95% CI, 0.84-0.94; P <.001). Concentrations of NT-proBNP remained lower at the 6-year follow-up in the treatment vs placebo group (P =.004).
Baseline levels of NT-proBNP ≥125 pg/mL were found to predict incidences of HF hospitalization (hazard ratio [HR], 5.40; 95% CI, 2.67-10.9), all-cause mortality (HR, 2.53; 95% CI, 1.78-3.61), and a composite of HF hospitalization or CV death (HR, 3.52; 95% CI, 2.38-5.20) after multivariable adjustment. Additionally, the adjusted HRs for patients with higher vs lower baseline NT-proBNP concentrations were the following: major adverse CV events (HR, 2.27; 95% CI, 1.69-3.05) and CV death (HR, 2.93; 95% CI, 1.87-4.60) as well as non-fatal myocardial infarction (HR, 1.95; 95% CI, 1.21-3.15) and non-fatal stroke (HR, 2.25; 95% CI, 1.26-4.01) (P <.001 for all).
When a subsequent mediation analysis was performed, only 10.4% of canagliflozin’s effects on HF hospitalization rates could be attributed to the drug’s ability to reduce NT-proBNP levels.
Study limitations include a lack of blood samples for all CANVAS participants, and lack of detailed left ventricular function characterization.
“These results help to address numerous questions about cardiovascular outcomes trials in type 2 diabetes, extend our understanding of how NT-proBNP predicts risk in these patients, and clarify the benefits of canagliflozin in the CANVAS trial,” noted the authors.
Funding and Conflicts of Interest Disclosures:
This work was supported by Janssen Research & Development, LLC.
Please see original article for conflict of interest declarations.
Reference Januzzi JL, Xu J, Li J, et al. Effects of canagliflozin on amino-terminal pro–B-type natriuretic peptide. J Am Coll Cardiol. 2020;76(18):2076-2085. doi:10.1016/j.jacc.2020.0