A Study to Learn How Safe Starting Vericiguat at a Dose of 5 Milligrams is in Participants With Chronic Heart Failure With Reduced Ejection Fraction

• Has an Left ventricle ejection fraction (LVEF) of \<45% assessed within 12 months before Visit 1 by local any imaging method, and no subsequent LVEF measurement > 45%. The most recent measurement must be used to determine eligibility.
• systolic blood pressure (SBP) ≥ 100 mmHg at screening and Visit 1 (pre-treatment).

• No changes in guideline-directed medical therapy for heart failure (GDMT) dosing (including beta blockers, angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker (ACEI/ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRAs), hydralazine-nitrate combinations, sodium-glucose cotransporter 2 i(SGLT2) inhibitors, ivabradine, or oral diuretics):

  • Within 4 weeks of screening for participants without a heart failure (HF) event ≤6 months prior to screening
  • within 2 weeks of screening for participants with a HF event ≤6 months prior to screening
  • planned during study participation
• No expected medical procedures to occur 2 weeks before screening or during study participation.
• Participants with ( group 1) OR without (group 2) recent worsening HF event Group 1: History of chronic HF (NYHA class II symptomatic-IV) on GDMT with recent HFevent within 6 months of screening or outpatient IV / SC diuretic use within 3 months before screening.

OR Group 2: History of chronic HF (NYHA class II symptomatic-IV) on GDMT without recent HF event within 6 months of screening or outpatient intravenous/ subcutaneous (IV / SC) diuretic use within 3 months before screening.

Exclusion Criteria:

• History of symptomatic hypotension 4 weeks before screening
• Primary valvular heart disease requiring surgical procedure or intervention or has undergone a vascular surgical procedure or intervention within 3months before visit 1
• Hypertrophic cardiomyopathy
• Acute myocarditis or Takotsubo cardiomyopathy
• Awaiting heart transplantation (United Network for Organ Sharing Class 1A /1B or equivalent) or has or anticipates receiving an implanted ventricular assist device, or has received a heart transplant.
• Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
• Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI), undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3months before Visit 1, or indication for coronary revascularization at the time of treatment assignment.
• Symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3 months before Visit 1.
• History of repaired or unrepaired simple congenital heart disease (e.g., atrial or ventricular septal defects, or patent ductus arteriosus) with ongoing hemodynamically significant residual lesions, or any history of complex congenital heart disease (e.g. tetralogy of Fallot, transposition of the great arteries, single ventricle disease) regardless of repair status.
• Active endocarditis or constrictive pericarditis.
• Hemodynamic instability or hypovolemia within 4 weeks of screening and during the screening period.
• Currently hospitalized.
• estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation of \<15 mL/min/1.73 m2 within 30 days before Visit 1 or on chronic dialysis. For participants with multiple eGFR results during screening, the most recent value will be used to determine eligibility.
• Severe hepatic insufficiency defined as albumin to bilirubin ratio (ALBI) Grade 3 or hepatic encephalopathy, or has hepatic laboratory abnormalities (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 ×upper limit of normal (ULN) or total bilirubin ≥2 × ULN). Exceptions for Gilbert's syndrome will be considered. Albumin, ALT, AST, and total bilirubin results within 30 days before Visit 1 may be used for assessment of laboratory abnormalities or the calculation of the ALBI score. For participants with multiple albumin and/or total bilirubin results during screening, the most recent value for each test will be used to calculate ALBI score.
• Malignancy or other noncardiac condition limiting life expectancy to \<3years.
• Requires continuous home oxygen for severe pulmonary disease.
• Interstitial lung disease.
• Known allergy or hypersensitivity to vericiguat, any of its constituents, or any other soluble guanylate cyclase (sGC) stimulator.
• Amyloidosis or sarcoidosis.
• Concurrent or anticipated concomitant use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and sildenafil during the study.
• Concurrent use of an sGC stimulator such as riociguat or vericiguat.
• Prior (within 2 weeks prior to screening) or anticipated concomitant administration of IV / SC diuretics or inotropes.