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.