Patient-reported outcomes in the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED ejection fraction (SOCRATES-PRESERVED) study

Abstract

Aims: Exploratory assessment of the potential benefits of the novel soluble guanylate cyclase stimulator vericiguat on health status in patients with heart failure (HF) with preserved ejection fraction.

Methods and results: The SOCRATES-PRESERVED trial randomized patients with chronic HF and ejection fraction ≥ 45% within 4 weeks of decompensation to 12 weeks of treatment with titrated doses of vericiguat (1.25, 2.5, 5, and 10 mg once daily) or placebo. Health status was assessed with the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) and the generic health-related quality of life measure EQ-5D. In total, 477 patients were randomized 12.9 ± 9.0 days after hospitalization or if requiring outpatient treatment with intravenous diuretics for HF. Baseline KCCQ clinical summary score (CSS), a combination of symptom and physical function domains, was 52.3 ± 20.4 in the 10 mg arm and 54.1 ± 23.0 in placebo, and EQ-5D US index score was 0.74 ± 0.2 and 0.73 ± 0.2, respectively. A larger proportion of patients treated with vericiguat in the 10 mg arm, compared with placebo, achieved clinically meaningful improvements in KCCQ-CSS (82.0% vs. 59.0%, number needed to treat = 4.35, P = 0.0052). Important domains of the KCCQ as well as EQ-5D scores demonstrated a dose-dependent relationship with vericiguat. In the 10 mg arm, the mean physical limitations domain increased by +17.2 ± 19.1 at 12 weeks, compared with +4.5 ± 21.6 in placebo (P = 0.0009). The EQ-5D US index score increased by +0.064 ± 0.167 in the 10 mg arm, compared with a decrease of -0.009 ± 0.195 in placebo (P = 0.0461). Improvements in KCCQ and EQ-5D scores paralleled physician-assessed NYHA class and clinical congestion.

Conclusion: Vericiguat, in exploratory hypothesis-generating analyses, was associated with clinically important improvements in patients' health status, as assessed by the KCCQ and EQ-5D. Further studies should be conducted to test the hypothesis that vericiguat improves physical functioning and health-related quality of life in patients with HF with preserved ejection fraction.

Keywords: Heart failure with preserved ejection fraction; Quality of life; Soluble guanylate cyclase stimulator.