CA-125-guided therapy may improve outcomes for acute heart failure vs. standard of care

Postdischarge therapy for acute heart failure guided by CA-125 levels may yield better outcomes than therapy based on the standard of care, according to a new study.

Researchers performed a multicenter trial in which patients who were discharged after a hospitalization for acute heart failure and who had high CA-125 levels (>35 U/mL) were randomly assigned to a CA-125 strategy or to standard of care. Carbohydrate antigen-125, or CA-125, is a membrane-associated mucin that may be elevated in certain malignant conditions; its most common use is as a tumor marker for ovarian cancer. However, CA-125 is also released from the surface of mesothelial cells in response to mechanical stress (such as fluid overload) and inflammatory stimuli; it therefore tends to be elevated in patients with heart failure, and its measurement has been proposed as a possible tool for helping manage this condition.

The CA-125 strategy aimed to reduce CA-125 levels to 35 U/mL or lower by increasing or decreasing the dose of diuretics, enforcing statin use, and closely monitoring the patient. The standard of care strategy was defined as care that followed standard guidelines on use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta-blockers, aldosterone antagonists, ivabradine, statins, diuretics, and other treatments (e.g., anticoagulants, antiarrhythmics, digoxin, nitrates and vasoactive drugs, devices, revascularization, and surgical procedures).

Patients were followed in outpatient heart failure clinics and had prespecified visits 1, 6, and 12 months after randomization. The study's primary endpoint was a 1-year composite of death and readmission for acute heart failure, with treatment strategies compared longitudinally and as time to first event. The study results were published online by JACC: Heart Failure.

Of 380 patients included in the trial, 187 were assigned to the CA-125 group and 193 were assigned to the standard of care group. Mean age of the study population was 73.7 years; 44.2% were women, and 40.3% had a left ventricular ejection fraction above 50%. During the trial, patients in the CA-125 group had more visits, both prespecified and optional, than those in the standard of care group (5.97 vs. 5.23 visits/person-years; incidence rate ratio, 1.14; P=0.003). No difference was seen between the groups in frequency of prescriptions for beta-blockers, ACE inhibitors, ARBs, or aldosterone-receptor blockers. Doses of aldosterone-receptor blockers and oral loop diuretics were more frequently modified in the CA-125 group. The CA-125 group had a significant reduction in the primary end point both longitudinally (85 vs. 165 recurrent events; incidence rate ratio, 0.49; 95% CI, 0.28 to 0.82; P=0.008) and as time to first event (66 vs. 84 events; P=0.017), due mainly to reduced hospitalizations rather than to reduced mortality.

The authors noted that their sample size was small, that the exclusion of patients with low-normal CA-125 levels may have affected the generalizability of their results, and that the physicians and nurses were not blinded to patients' group assignment, among other limitations. However, they concluded that patients who are discharged after hospitalization for acute heart failure may benefit from a management strategy that aims to keep CA-125 levels below 35 U/mL. They called for larger studies to confirm their results and better quantify the potential clinical impact of this approach.