Chronic Heart Failure With Reduced Ejection Fraction
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of vericiguat in participants with chronic heart failure with reduced ejection fraction (HFrEF), specifically those with symptomatic chronic HFrEF who have not had a recent hospitalization for heart failure or need for outpatient intravenous (IV) diuretics. The primary hypothesis is that vericiguat is superior to placebo in reducing the risk of cardiovascular death or heart failure hospitalization.
Interventions
DRUGVericiguat
2.5, 5.0, or 10.0 mg orally once daily
DRUGPlacebo
0 mg matching placebo for 2.5 mg, 5 mg, and 10 mg of vericiguat
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of chronic HF \[New York Heart Association (NYHA) Class II to IV\] on guideline-directed medical therapy for heart failure (GDMT) with no HF hospitalization within 6 months or outpatient IV diuretic use within 3 months before randomization. * Left ventricular ejection fraction (LVEF) of ≤40%, assessed within 12 months before randomization by any imaging method. * Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. * A female participant is eligible to participate if she is not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during the study intervention period and for at least 1 month after the last dose of study intervention.
Exclusion criteria
* Has SBP \<100 mm Hg or symptomatic hypotension. * Awaiting heart transplantation, is receiving continuous IV infusion of an inotrope, or has or anticipates receiving an implanted ventricular assist device. * Amyloidosis or sarcoidosis. * Primary valvular heart disease requiring surgical procedure or intervention or has undergone a valvular surgical procedure or intervention within 3 months before randomization. * Hypertrophic cardiomyopathy. * Acute myocarditis or Takotsubo cardiomyopathy. * History of heart transplant. * Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia. * Acute coronary syndrome, or undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3 months before randomization. * History of symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3 months before randomization. * Malignancy or other noncardiac condition limiting life expectancy to \<3 years. * Requires continuous home oxygen for severe pulmonary disease. * Interstitial lung disease. * Discontinuation or dose modification of GDMT or vericiguat within 4 weeks before randomization. * Recent history (within the last year) of drug or alcohol abuse or dependence.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years | Up to approximately 36 months (from randomization to the primary completion data cutoff) | The time to first occurrence of the composite endpoint of CV death or HF hospitalization was defined as the time from randomization to the first event of CV death or HF hospitalization. Randomized participants without a HF hospitalization or CV death event at the time of analysis were censored at the last available information, when the protocol pre-specified number of total CV death events was achieved (primary completion analysis data cutoff), or the date of their non-CV death, whichever occurred first. Events were confirmed by a clinical events committee (CEC). Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with a CV death or HF hospitalization event per 100 patient-years at risk is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of HF Hospitalization: Participants With an Event Per 100 Patient-Years | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Time to first occurrence of HF hospitalization was defined as the time from randomization to the first event of HF hospitalization. Randomized participants without an HF hospitalization at the time of analysis were censored at their last available information, when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), or the date of their death, whichever occurred first. HF hospitalizations were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with an HF hospitalization event per 100 patient-years at risk is presented. |
| Time to Total HF Hospitalizations (Including First and Recurrent Events): Total Events Per 100 Patient-Years | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Time to total HF hospitalizations was defined as the time from randomization to all HF hospitalization events, including time to first event and time increments between events. Randomized participants without an HF hospitalization at the time of analysis were censored at their last available information, when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), or the date of their death, whichever occurred first. HF hospitalizations were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of total HF hospitalization events per 100 patient-years at risk is presented. |
| Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization: Participants With an Event Per 100 Patient-Years | Up to approximately 36 months (from randomization to the primary completion data cutoff) | The time to first occurrence of the composite endpoint of all-cause mortality or HF hospitalization was defined as the time from randomization to the first event of all-cause mortality or HF hospitalization. Randomized participants without an all-cause mortality or HF hospitalization event at the time of analysis were censored at the last available information or when the protocol pre-specified number of total CV death events is achieved (primary analysis database cutoff), whichever occurred first. Events were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with an all-cause mortality or HF hospitalization event per 100 patient-years at risk is presented. |
| Time to All-Cause Mortality: Participants With an Event Per 100 Patient-Years | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Time to all-cause mortality was defined as the time from randomization to all-cause mortality. Randomized participants without an all-cause mortality event at the time of analysis were censored at their last available information or when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), whichever occurred first. All-cause mortality was confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with an all-cause mortality event per 100 patient-years at risk is presented. |
| Percentage of Participants Who Experienced One or More Selected Nonserious Adverse Events (NSAEs) | Up to approximately 36 months (from randomization to the primary completion data cutoff) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Selected NSAEs are defined as nonserious AEs that meet any of the following criteria: AEs that lead to study intervention dose modification or discontinuation, AEs that lead to withdrawal from the study, or Coronavirus Disease 2019 (COVID-19) disease-related AEs. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more selected NSAEs is presented. |
| Time to CV Death: Participants With an Event Per 100 Patient-Years | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Time to CV death was defined as the time from randomization to CV death. Randomized participants without a CV death at the time of analysis were censored at their last available information, when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), or the date of their non-CV death, whichever occurred first. CV deaths were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with a CV death event per 100 patient-years at risk is presented. |
| Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECIs) | Up to approximately 36 months (from randomization to the primary completion data cutoff) | ECIs were determined and reported based on the clinical judgment of the investigator. As pre-specified in the protocol, ECIs included the following: 1) Events of potential drug-induced liver injury (DILI), defined as an elevated aspartate aminotransferase or alanine aminotransferase laboratory value that is greater than or equal to 3X the upper limit of normal (ULN) and an elevated total bilirubin laboratory value that is greater than or equal to 2X the ULN and, at the same time, an alkaline phosphatase laboratory value that is less than 2X the ULN, 2) Events associated with symptomatic hypotension, or 3) Events associated with anemia, regardless of etiology. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more ECIs is presented. |
| Percentage of Participants Who Experienced One or More Potential DILI ECIs | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Potential DILI ECIs were determined and reported based on the clinical judgment of the investigator. Potential DILI ECIs were defined as an elevated aspartate aminotransferase or alanine aminotransferase laboratory value that is greater than or equal to 3X the ULN and an elevated total bilirubin laboratory value that is greater than or equal to 2X the ULN and, at the same time, an alkaline phosphatase laboratory value that is less than 2X the ULN. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more potential DILI ECIs is presented. |
| Percentage of Participants Who Experienced One or More Symptomatic Hypotension ECIs | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Symptomatic hypotension ECIs were determined and reported based on the clinical judgment of the investigator. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more symptomatic hypotension ECIs is presented. |
| Percentage of Participants Who Experienced One or More Anemia ECIs | Up to approximately 36 months (from randomization to the primary completion data cutoff) | Anemia ECIs were determined and reported based on the clinical judgment of the investigator, regardless of etiology. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more anemia ECIs is presented. |
| Percentage of Participants Who Experienced One or More Serious Adverse Events (SAEs) | Up to approximately 36 months (from randomization to the primary completion data cutoff) | An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or other important medical events as determined by the investigator. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more SAEs is presented. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Malaysia, Mexico, New Zealand, Peru, Poland, Puerto Rico, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Of 10923 participants screened, 6106 participants were randomized in a 1:1 ratio to receive either vericiguat or matching placebo. One participant was randomized in the study at 2 different clinical study sites. Due to double enrolment and study site noncompliance with Good Clinical Practice (GCP), this participant was excluded from all efficacy and safety analyses. Results are presented based on 6105 randomized participants.
Participants by arm
| Arm | Count |
|---|---|
| Vericiguat Participants received a starting dose of 2.5 mg of vericiguat taken orally once daily for 2 weeks. The vericiguat dose was titrated to 5 mg for 2 weeks and then to the target dose of 10 mg for the remainder of treatment (total treatment of up to approximately 37 months). | 3,053 |
| Placebo Participants received a placebo matched to the vericiguat dose of 2.5 mg taken orally once daily for 2 weeks. The placebo dose was sham titrated to 5 mg for 2 weeks and then to 10 mg for the remainder of treatment (total treatment of up to approximately 37 months). | 3,052 |
| Total | 6,105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 372 | 434 |
| Overall Study | Lost to Follow-up | 13 | 16 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Sponsor Decision | 1 | 3 |
| Overall Study | Withdrawal by Guardian | 1 | 1 |
| Overall Study | Withdrawal by Subject | 18 | 25 |
Baseline characteristics
| Characteristic | Vericiguat | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 67.1 Years STANDARD_DEVIATION 11 | 67.0 Years STANDARD_DEVIATION 11 | 67.0 Years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 968 Participants | 1921 Participants | 953 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2044 Participants | 4112 Participants | 2068 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 41 Participants | 72 Participants | 31 Participants |
| New York Heart Association (NYHA) Functional Classification (FC) of Heart Failure NYHA Class II | 2411 Participants | 4822 Participants | 2411 Participants |
| New York Heart Association (NYHA) Functional Classification (FC) of Heart Failure NYHA Class III/IV | 642 Participants | 1283 Participants | 641 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 159 Participants | 301 Participants | 142 Participants |
| Race (NIH/OMB) Asian | 383 Participants | 746 Participants | 363 Participants |
| Race (NIH/OMB) Black or African American | 251 Participants | 469 Participants | 218 Participants |
| Race (NIH/OMB) More than one race | 313 Participants | 643 Participants | 330 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 1942 Participants | 3934 Participants | 1992 Participants |
| Sex: Female, Male Female | 727 Participants | 1440 Participants | 713 Participants |
| Sex: Female, Male Male | 2326 Participants | 4665 Participants | 2339 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 392 / 3,053 | 455 / 3,052 |
| other Total, other adverse events | 530 / 3,049 | 423 / 3,049 |
| serious Total, serious adverse events | 732 / 3,049 | 766 / 3,049 |
Outcome results
Primary
Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years
The time to first occurrence of the composite endpoint of CV death or HF hospitalization was defined as the time from randomization to the first event of CV death or HF hospitalization. Randomized participants without a HF hospitalization or CV death event at the time of analysis were censored at the last available information, when the protocol pre-specified number of total CV death events was achieved (primary completion analysis data cutoff), or the date of their non-CV death, whichever occurred first. Events were confirmed by a clinical events committee (CEC). Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with a CV death or HF hospitalization event per 100 patient-years at risk is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years | 11.3 Pts. with event/100 patient-yrs at risk |
| Placebo | Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization: Participants With an Event Per 100 Patient-Years | 12.2 Pts. with event/100 patient-yrs at risk |
p-value: 0.21995% CI: [0.83, 1.04]Log Rank
Secondary
Percentage of Participants Who Experienced One or More Anemia ECIs
Anemia ECIs were determined and reported based on the clinical judgment of the investigator, regardless of etiology. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more anemia ECIs is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who received at least 1 dose of study intervention and who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Percentage of Participants Who Experienced One or More Anemia ECIs | 7.6 Percentage of Participants |
| Placebo | Percentage of Participants Who Experienced One or More Anemia ECIs | 6.3 Percentage of Participants |
p-value: 0.04595% CI: [0, 2.6]Miettinen and Nurminen
Secondary
Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECIs)
ECIs were determined and reported based on the clinical judgment of the investigator. As pre-specified in the protocol, ECIs included the following: 1) Events of potential drug-induced liver injury (DILI), defined as an elevated aspartate aminotransferase or alanine aminotransferase laboratory value that is greater than or equal to 3X the upper limit of normal (ULN) and an elevated total bilirubin laboratory value that is greater than or equal to 2X the ULN and, at the same time, an alkaline phosphatase laboratory value that is less than 2X the ULN, 2) Events associated with symptomatic hypotension, or 3) Events associated with anemia, regardless of etiology. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more ECIs is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who received at least 1 dose of study intervention and who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECIs) | 17.6 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced One or More Events of Clinical Interest (ECIs) | 14.6 Percentage of participants |
Secondary
Percentage of Participants Who Experienced One or More Potential DILI ECIs
Potential DILI ECIs were determined and reported based on the clinical judgment of the investigator. Potential DILI ECIs were defined as an elevated aspartate aminotransferase or alanine aminotransferase laboratory value that is greater than or equal to 3X the ULN and an elevated total bilirubin laboratory value that is greater than or equal to 2X the ULN and, at the same time, an alkaline phosphatase laboratory value that is less than 2X the ULN. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more potential DILI ECIs is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who received at least 1 dose of study intervention and who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Percentage of Participants Who Experienced One or More Potential DILI ECIs | 0.3 Percentage of Participants |
| Placebo | Percentage of Participants Who Experienced One or More Potential DILI ECIs | 0.4 Percentage of Participants |
p-value: 0.51295% CI: [-0.4, 0.2]Miettinen and Nurminen
Secondary
Percentage of Participants Who Experienced One or More Selected Nonserious Adverse Events (NSAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Selected NSAEs are defined as nonserious AEs that meet any of the following criteria: AEs that lead to study intervention dose modification or discontinuation, AEs that lead to withdrawal from the study, or Coronavirus Disease 2019 (COVID-19) disease-related AEs. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more selected NSAEs is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who received at least 1 dose of study intervention and who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Percentage of Participants Who Experienced One or More Selected Nonserious Adverse Events (NSAEs) | 19.7 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced One or More Selected Nonserious Adverse Events (NSAEs) | 16.9 Percentage of participants |
Secondary
Percentage of Participants Who Experienced One or More Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or other important medical events as determined by the investigator. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more SAEs is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who received at least 1 dose of study intervention and who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Percentage of Participants Who Experienced One or More Serious Adverse Events (SAEs) | 23.5 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced One or More Serious Adverse Events (SAEs) | 24.6 Percentage of participants |
Secondary
Percentage of Participants Who Experienced One or More Symptomatic Hypotension ECIs
Symptomatic hypotension ECIs were determined and reported based on the clinical judgment of the investigator. Protocol-specified final analyses are reported here with a primary completion data cutoff. The percentage of participants who experienced one or more symptomatic hypotension ECIs is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who received at least 1 dose of study intervention and who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Percentage of Participants Who Experienced One or More Symptomatic Hypotension ECIs | 11.3 Percentage of Participants |
| Placebo | Percentage of Participants Who Experienced One or More Symptomatic Hypotension ECIs | 9.2 Percentage of Participants |
p-value: 0.00795% CI: [0.6, 3.6]Miettinen and Nurminen
Secondary
Time to All-Cause Mortality: Participants With an Event Per 100 Patient-Years
Time to all-cause mortality was defined as the time from randomization to all-cause mortality. Randomized participants without an all-cause mortality event at the time of analysis were censored at their last available information or when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), whichever occurred first. All-cause mortality was confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with an all-cause mortality event per 100 patient-years at risk is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Time to All-Cause Mortality: Participants With an Event Per 100 Patient-Years | 7.3 Pts. with event/100 patient-yrs at risk |
| Placebo | Time to All-Cause Mortality: Participants With an Event Per 100 Patient-Years | 8.6 Pts. with event/100 patient-yrs at risk |
p-value: 0.01595% CI: [0.74, 0.97]Log Rank
Secondary
Time to CV Death: Participants With an Event Per 100 Patient-Years
Time to CV death was defined as the time from randomization to CV death. Randomized participants without a CV death at the time of analysis were censored at their last available information, when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), or the date of their non-CV death, whichever occurred first. CV deaths were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with a CV death event per 100 patient-years at risk is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Time to CV Death: Participants With an Event Per 100 Patient-Years | 5.7 Pts. with event/100 patient-yrs at risk |
| Placebo | Time to CV Death: Participants With an Event Per 100 Patient-Years | 6.8 Pts. with event/100 patient-yrs at risk |
p-value: 0.0295% CI: [0.71, 0.97]Log Rank
Secondary
Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization: Participants With an Event Per 100 Patient-Years
The time to first occurrence of the composite endpoint of all-cause mortality or HF hospitalization was defined as the time from randomization to the first event of all-cause mortality or HF hospitalization. Randomized participants without an all-cause mortality or HF hospitalization event at the time of analysis were censored at the last available information or when the protocol pre-specified number of total CV death events is achieved (primary analysis database cutoff), whichever occurred first. Events were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with an all-cause mortality or HF hospitalization event per 100 patient-years at risk is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization: Participants With an Event Per 100 Patient-Years | 12.7 Pts. with event/100 patient-yrs at risk |
| Placebo | Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization: Participants With an Event Per 100 Patient-Years | 13.9 Pts. with event/100 patient-yrs at risk |
p-value: 0.11695% CI: [0.82, 1.02]Log Rank
Secondary
Time to First Occurrence of HF Hospitalization: Participants With an Event Per 100 Patient-Years
Time to first occurrence of HF hospitalization was defined as the time from randomization to the first event of HF hospitalization. Randomized participants without an HF hospitalization at the time of analysis were censored at their last available information, when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), or the date of their death, whichever occurred first. HF hospitalizations were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with an HF hospitalization event per 100 patient-years at risk is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Time to First Occurrence of HF Hospitalization: Participants With an Event Per 100 Patient-Years | 7.2 Pts. with event/100 patient-yrs at risk |
| Placebo | Time to First Occurrence of HF Hospitalization: Participants With an Event Per 100 Patient-Years | 7.6 Pts. with event/100 patient-yrs at risk |
p-value: 0.50995% CI: [0.82, 1.1]Log Rank
Secondary
Time to Total HF Hospitalizations (Including First and Recurrent Events): Total Events Per 100 Patient-Years
Time to total HF hospitalizations was defined as the time from randomization to all HF hospitalization events, including time to first event and time increments between events. Randomized participants without an HF hospitalization at the time of analysis were censored at their last available information, when the protocol pre-specified number of total CV death events was achieved (primary analysis database cutoff), or the date of their death, whichever occurred first. HF hospitalizations were confirmed by a CEC. Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of total HF hospitalization events per 100 patient-years at risk is presented.
Time frame: Up to approximately 36 months (from randomization to the primary completion data cutoff)
Population: All randomized participants who had GCP-compliant data collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vericiguat | Time to Total HF Hospitalizations (Including First and Recurrent Events): Total Events Per 100 Patient-Years | 10.7 Total events/100 patient-yrs at risk |
| Placebo | Time to Total HF Hospitalizations (Including First and Recurrent Events): Total Events Per 100 Patient-Years | 11.8 Total events/100 patient-yrs at risk |
p-value: 0.09495% CI: [0.8, 1.02]Andersen-Gill Model