Patients with worsening chronic heart failure and reduced left ventricular ejection fraction (LVEF) who were prescribed vericiguat did not exhibit statistically significant results, compared with a placebo, suggests research published in JAMA and presented at the American Heart Association’s 2015 Scientific Sessions.

Mihai Gheorghiade, MD, from the Northwestern University Feinberg School of Medicine, and colleagues conducted the phase 2 SOCRATES-REDUCED study to determine the optimal dose and tolerability of vericiguat to reduce elevated natriuretic peptide levels, produced in response to high pressure inside the heart, a typical effect of heart failure. Elevated natriuretic peptide levels correlate with worsening heart failure, severity of symptoms, and risk of death.

Dr. Gheorghiade and colleagues studied 456 patients with worsening chronic heart failure and LVEF. Patients randomly received either daily doses of vericiguat or a placebo for 12 weeks. Overall, 351 patients – 77% – completed treatment, although any change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was not statistically significant. However, a secondary analysis suggested a dose-response relationship; higher vericiguat doses were associated with greater reductions in NT-proBNP.

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“Vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated,” wrote Dr. Gheorghiade and colleagues. “Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic heart failure.”


  1. Gheorghiade M, Green SJ, Butler J, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA. 2015; doi: 10.1001/jama.2015.15734