Intervention: Vericiguat
Trial phase: Phase 3
ATC code: C01DX22
SMILES: COC(=O)Nc1c(N)nc(-c2nn(Cc3ccccc3F)c3ncc(F)cc23)nc1N
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2519
Group description: Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose was uptitrated to 5 mg and to 10 mg.
Eligibility criteria:
Inclusion Criteria:

History of chronic HF (New York Heart Association [NYHA] Class II-IV) on standard therapy before qualifying HF decompensation
Previous HF hospitalization within 6 months prior to randomization or intravenous (IV) diuretic treatment for HF (without hospitalization) within 3 months.
Brain natriuretic peptide (BNP) levels: sinus rhythm-≥ 300 pg/mL; atrial fibrillation-≥ 500 pg/mL and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels: sinus rhythm- ≥ 1000 pg/mL; atrial fibrillation - ≥ 1600 pg/mL within 30 days prior to randomization
Left ventricular ejection fraction (LVEF) of <45% assessed within 12 months prior to randomization by any method
If female, is not of reproductive potential or agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: practice abstinence from heterosexual activity or use (or have her partner use) acceptable contraception during heterosexual activity.

Exclusion Criteria:

Clinically unstable at the time of randomization as defined by either the administration of any IV treatment within 24 hours prior to randomization, and/or systolic blood pressure (SBP) <100 mmHg or symptomatic hypotension
Current or anticipated use of long-acting nitrates or nitric oxide (NO) donors including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine
Current or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and sildenafil
Current use or anticipated use of a soluble guanylate cyclase (sGC) stimulator such as riociguat
Known allergy or sensitivity to any sGC stimulator
Awaiting heart transplantation (United Network for Organ Sharing Class 1A / 1B or equivalent), receiving continuous IV infusion of an inotrope, or has/anticipates receiving an implanted ventricular assist device
Primary valvular heart disease requiring surgery or intervention, or is within 3 months after valvular surgery or intervention
Hypertrophic obstructive cardiomyopathy
Acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy
Post-heart transplant cardiomyopathy
Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia
Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction [NSTEMI], or ST elevation myocardial infarction [(STEMI]) or coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) within 60 days, or indication for coronary revascularization at time of randomization
Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days
Complex congenital heart disease
Active endocarditis or constrictive pericarditis
Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 or chronic dialysis
Severe hepatic insufficiency such as with hepatic encephalopathy
Malignancy or other non-cardiac condition limiting life expectancy to <3 years
Require continuous home oxygen for severe pulmonary disease
Current alcohol and/or drug abuse
Participated in another interventional clinical study and treatment with another investigational product ≤30 days prior to randomization or plans to participate in any other trial/investigation during the duration of this study
Mental or legal incapacitation and is unable to provide informed consent
Immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is involved with this study
Interstitial Lung Disease
Is pregnant or breastfeeding or plans to become pregnant or to breastfeed during the course of the study