An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.

Safety Population consisted of all randomized participants who took at least 1 dose of study drug.

Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min

Evaluable Population consisted of all participants in the modified (m)ITT population who completed 8 weeks of dosing (±3 days) and had at least 1 evaluable post-Baseline assessment and did not have a dose reduction. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.

6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.

Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.

Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.

Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.

CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.

Evaluable Population. Only those participants with data available at the specified data points were analyzed. Following protocol amendment 3, efficacy analyses included only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis.