6/29/23, 1:10 AM RELAX Pathway Feedback Search Clinical Topics Home Studies RELAX RELAX Disease Heart failure Trial question What is the effect of PDE5 inhibition on exercise capacity and clinical status in patients with HFpEF? Study design Multi-center Double blinded RCT Population Characteristics of study participants 48.0% female N = 216 52.0% male 216 patients (104 female, 112 male) Inclusion criteria: stable outpatients with HF, ejection fraction 50%, elevated N-terminal brain- type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity Key exclusion criteria: pericardial disease, hypertrophic cardiomyopathy, primary pulmonary arteriopathy, anemia, severe liver disease, severe renal dysfunction, or listed for cardiac transplantation Interventions N=113 sildenafil (administered PO at 20 mg, TID for 12 weeks, followed by 60 mg, TID for 12 weeks) https://web.pathway.md/studies/reclymLtwkkpeEk33 1/2 6/29/23, 1:10 AM RELAX Pathway N=103 placebo (matching placebo for 24 weeks) Primary outcome Mean clinical status rank score at 24 weeks 95.8 95.8 94.2 71.8 47.9 23.9 No significant difference 0.0 Sildenafil Placebo No significant difference in mean clinical status rank score at 24 weeks (94.2 vs. 95.8; MD 1.6, 95% CI -13.87 to 17.07) Secondary outcomes No significant difference in change in 6-minute walk distance (5 m vs. 15 m; MD 10, 95% CI -169.3 to 189.3) Safety outcomes No significant differences in adverse events (80% vs. 76%, p=0.49) and serious adverse events (22% vs. 16%, p=0.22). Conclusion In stable outpatients with HF, ejection fraction 50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity, sildenafil was not superior to placebo with respect to mean clinical status rank score at 24 weeks. Reference Redfield MM, Chen HH, Borlaug BA et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013 Mar 27;309(12):1268-77. Open reference URL https://web.pathway.md/studies/reclymLtwkkpeEk33 2/2