Association of Carbohydrate Antigen 125 on the Response to Dapagliflozin in Patients With Heart Failure

BACKGROUND Elevated circulating carbohydrate antigen 125 (CA125) is a marker of congestion and a predictor of outcomes in acute heart failure (HF). Less is known about CA125 in chronic ambulatory HF with reduced ejection fraction.OBJECTIVES This study examined the association between baseline CA125 (and changes in CA125) and outcomes in patients with HF with reduced ejection fraction in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; NCT03036124) trial and its relationship with the effect of dapagliflozin.METHODS The primary outcome was a composite of a first episode of worsening HF or cardiovascular death. CA125 was measured at baseline and 12 months following randomization.RESULTS Median baseline CA125 was 13.04 U/mL (IQR: 8.78-21.13 U/mL) in 3,123 of 4,774 patients with available data. Compared with CA125 #35 U/mL (upper limit of normal), patients with CA125 >35 U/mL were at a higher risk of the primary outcome (adjusted HR: 1.59; 95% CI: 1.29-1.96). The adjusted risks of the primary outcome relative to quartile 1 (Q1) (#8.78 U/mL) were as follow: Q2, 8.79-13.04 U/mL (HR: 0.94; 95% CI: 0.71-1.24); Q3, 13.05-21.13 U/mL (HR: 1.22; 95% CI: 0.94-1.59); Q4, $21.14 U/mL (HR: 1.63; 95% CI: 1.28-2.09). The beneficial effect of dapagliflozin compared with placebo on the primary outcome was consistent whether CA125 was analyzed in quartiles (interaction P = 0.13) or as a continuous variable (interaction P = 0.75). The placebo-corrected relative change in CA125 at 12 months was -5.2% (95% CI: -10.6% to 0.5%; P = 0.07). CONCLUSIONS In DAPA-HF, elevated CA125 levels were an independent predictor of the risk of worsening HF or cardiovascular death. Dapagliflozin reduced the risk of worsening HF or cardiovascular death regardless of baseline CA125. (J Am Coll Cardiol 2023;82:142-15 7)& COPY; 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study examined the association between baseline CA125 levels and outcomes in patients with chronic ambulatory HF with reduced ejection fraction, and investigated the effect of dapagliflozin. The results show that elevated CA125 levels are an independent predictor of the risk of worsening HF or cardiovascular death, while dapagliflozin reduces the risk of worsening HF or cardiovascular death regardless of baseline CA125 levels.