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

Inclusion Criteria:

• Has an Left ventricle ejection fraction (LVEF) of <45% assessed within 12 monthsbefore 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 IIreceptor 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 toscreening

• planned during study participation

• No expected medical procedures to occur 2 weeks before screening or during studyparticipation.

• 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 HFeventwithin 6 months of screening or outpatient IV / SC diuretic use within 3 monthsbefore 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 hasundergone 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 orequivalent) 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 arterybypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3monthsbefore Visit 1, or indication for coronary revascularization at the time oftreatment assignment.

• Symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3months before Visit 1.

• History of repaired or unrepaired simple congenital heart disease (e.g., atrial orventricular septal defects, or patent ductus arteriosus) with ongoinghemodynamically significant residual lesions, or any history of complex congenitalheart disease (e.g. tetralogy of Fallot, transposition of the great arteries, singleventricle disease) regardless of repair status.

• Active endocarditis or constrictive pericarditis.

• Hemodynamic instability or hypovolemia within 4 weeks of screening and during thescreening period.

• Currently hospitalized.

• estimated glomerular filtration rate (eGFR) based on the Chronic Kidney DiseaseEpidemiology Collaboration (CKD-EPI) Creatinine Equation of <15 mL/min/1.73 m2within 30 days before Visit 1 or on chronic dialysis. For participants with multipleeGFR results during screening, the most recent value will be used to determineeligibility.

• Severe hepatic insufficiency defined as albumin to bilirubin ratio (ALBI) Grade 3 orhepatic encephalopathy, or has hepatic laboratory abnormalities (alanineaminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 ×upper limit of normal (ULN) or total bilirubin ≥2 × ULN). Exceptions for Gilbert's syndrome will beconsidered. Albumin, ALT, AST, and total bilirubin results within 30 days beforeVisit 1 may be used for assessment of laboratory abnormalities or the calculation ofthe ALBI score. For participants with multiple albumin and/or total bilirubinresults during screening, the most recent value for each test will be used tocalculate 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 anyother 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 administrationof IV / SC diuretics or inotropes.