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Markus Follmann, Corina Becker, Lothar Roessig, Peter Sandner, and Johannes‐Peter Stasch

Research & Development, Pharmaceuticals, Bayer AG, Aprather Weg 18a, 42096, Wuppertal, Germany

Despite better therapies, cardiovascular (CV) diseases remain the leading cause of death worldwide. Among them, heart failure (HF) is a leading cause of hospitalization and CV death [1]. More than 63 million people worldwide suffered from HF in 2016 [2], and around 50% of patients with HF die within five years [3]. HF, by definition, is a condition where the heart is unable to pump sufficiently in order to provide adequate blood flow to other organs such as the kidneys and the brain. Overall, it is a complex clinical syndrome caused by cardiac structural abnormalities and/or functional impairments. In general, HF is a chronic, progressive condition associated with significant morbidity and mortality. Main treatments include healthy lifestyle changes, in some cases surgery and implantation of devices to control heart rhythm, and pharmacotherapy. Prescribed drugs for heart failure with reduced ejection fraction (HFrEF) include angiotensin‐converting enzyme inhibitors, angiotensin‐2 receptor blockers (ARBs) or an angiotension receptor neprilysin inhibitor (ARNI), beta blockers, mineralocorticoid receptor antagonists, diuretics, and more recently SGLT‐2 (sodium glucose co‐transporter‐2) inhibitors. However, even with these new entrants and optimal guideline‐directed medical therapy, event rates in HFrEF remain as high as 15% per year of the composite outcome CV death or HF hospitalization in the empagliflozin arm of EMPEROR‐REDUCED [4] and even 38% in patients with HFrEF after a previous event in the placebo group of VICTORIA [5]. Therefore, the unmet need in HF is still high and drugs targeting other pathways involved in disease progression are sought. No less than 1 out of 6 patients suffering from HFrEF develop worsening HF on average 1.5 years following initial HF diagnosis. The high risk for two‐year mortality and recurrent HF hospitalizations in these patients indicates particularly high unmet medical need for novel treatment strategies [1]. Here we present the discovery and development of the soluble guanylate cyclase (sGC) stimulator vericiguat (BAY 1021189; MK‐1242) for the treatment of chronic HF. Data from the phase 3 VICTORIA trial in patients with worsening chronic HF and ejection fraction <45% were published in the New England Journal of Medicine [5, 6]. Vericiguat 10 mg once daily significantly reduced the combined risk of first HF hospitalization or CV death ( Figure 3.1).