Although the primary analysis of the primary end point was not achieved, compared to placebo, patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF) receiving vericiguat 10mg daily experienced a greater reduction in NT-proBNP, greater improvement in LVEF, and fewer clinical events.  This JAMA study is being released to coincide with its presentation at the American Heart Association's Scientific Sessions 2015.

Worsening chronic heart failure (WCHF) is a major public health problem around the world. Despite an often rapid and substantial in-hospital improvement in HF signs and symptoms with standard therapy, approximately 25 percent of patients are rehospitalized within 30 days and 30 percent of patients may die within 1 year.

The SOCRATES-REDUCED trial was a phase II, dose-finding study of stable patients with LVEF<45% within 4 weeks of a WCHF event. This study, which included patients from across Europe, North America, and Asia, was conducted to determine the optimal dose and tolerability of the drug vericiguat to reduce elevated natriuretic peptide levels.

Mihai Gheorghiade, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues randomly assigned 456 patients with WCHF and reduced LVEF to receive placebo or 1 of 4 daily target doses of the medication vericiguat for 12 weeks.

Overall, 351 patients (77 percent) completed treatment with the study drug with valid 12-week N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and no major protocol deviation. In the primary analysis, change in NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group and placebo. The secondary analysis suggested a dose-response relationship, such that higher vericiguat doses were associated with greater reductions in NT-proBNP level. Rates of any adverse event were 77 percent and 71 percent among the placebo and 10-mg vericiguat groups, respectively.

Although the primary analysis of the primary end point was not achieved, compared to placebo, patients receiving vericiguat 10mg daily experienced a greater reduction in NT-proBNP, greater improvement in LVEF, and fewer clinical events. As titrated in this study, vericiguat doses up to 10 mg daily were safe and did not meaningfully influence blood pressure and heart rate at 12 weeks.

"Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. 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 HF," the authors write.

This study was funded by affiliates of Bayer and Merck Sharp & Dahme, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey.