A Study of Vericiguat (MK-1242) in Participants With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-035)

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 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 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 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.

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 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.

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.

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.

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.

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.

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.

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.