CA125 biomarker may predict worse outcomes in patients of heart failure with reduced EF: JACC

The study, published in the Journal of the American College of Cardiology, revealed that patients with high CA125 levels at baseline were likelier to have a first episode of worsening heart failure or cardiovascular death (primary outcome) than those with lower levels even after adjustment for NT-proBNP and other biomarkers. Similar relationships were seen for all-cause mortality, HF death, and total HF hospitalizations/CV death.

Moreover, dapagliflozinb was reported to reduce the risk of worsening heart failure or cardiovascular (CV) death regardless of baseline levels of circulating CA125. This biomarker initially emerged in the setting of ovarian cancer and has since been studied in acute HF as a marker of congestion.

The DAPA-HF is a randomized, double-masked, placebo-controlled trial that involved 4,744 patients, of which 3,123 had a baseline measurement of CA125 and 2,427 had a second measurement at 12 months.

The analysis included 2,743 patients with a baseline CA125 concentration of ≤35 U/mL, of whom 1,384 (50.5%) were randomized to 10 mg once daily dapagliflozin treatment. The median age was 67.1±10.5 years, and 22.5% were females. Three hundred eighty patients were found to have a baseline CA125 concentration of >35 U/mL, of whom 195 (51.3%) were randomized to dapagliflozin treatment. The median age was 68.4±9.5 years, and 19.5% were females.

The trial's primary outcome was the composite of time to first worsening heart failure or CV death. The original trial had shown that the dapagliflozin arm had a lower rate of the primary outcome than the placebo arm.

The KCCQ-TSS (Kansas City Cardiomyopathy Questionnaire total symptom score) with a range of 0 to 100 was used (a higher score indicates fewer symptoms, and a ≥5 change is considered clinically meaningful).

The analysis revealed the following findings:

• Results of the DAPA-HF analysis reveal the median baseline of CA125 was 13.04 U/mL (interquartile range [IQR]: 8.78-21.13 U/mL) in the 3,123 patients with available data.
• Compared with CA125 ≤35 U/mL, patients with CA125 >35 U/mL were at a higher risk of the primary outcome (adjusted hazard ratio [HR]: 1.59).
• The adjusted risks of the primary outcome relative to quartile 1 (Q1) (≤8.78 U/mL) were as follows: Q2, 8.79-13.04 U/mL (HR: 0.94); Q3, 13.05-21.13 U/mL (HR: 1.22); Q4, ≥21.14 U/mL (HR: 1.63).

"The findings showed a 6-fold higher risk of the primary composite outcome in patients in whom CA125 increased above 35 U/mL at one year from baseline as compared with those in whom CA125 remained ≤35 U/mL," Kieran F. Docherty, the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, and colleagues wrote.

They added, "Dapagliflozin's efficacy compared with placebo in reducing the risk of worsening HF or CV death was consistent across the range of CA125 at baseline."

This finding is consistent with previous reports of no modification of the effect of SGLT2 inhibitors in HFrEF by diuretic use, NT-proBNP levels in patients with a history of previous HF hospitalization or in patients evaluated to have recently been volume-overloaded.

Reference:

Docherty KF, McDowell K, Welsh P, et al. Association of carbohydrate antigen 125 on the response to dapagliflozin in patients with heart failure. J Am Coll Cardiol. 2023;82(2):142-157.