PDE-5 Inhibition for Heart Failure

The primary endpoint was the change in peak VO₂ after 24 weeks of therapy. A number of subgroup analyses were pre-specified. Secondary endpoints included a composite hierarchical-rank clinical score where patients were ranked (range 1-N with data) based on time-to-death (tier 1), time-to-hospitalization for cardiovascular or cardiorenal causes (tier 2), and change in MLHFQ from baseline (tier 3) for patients alive without cardiovascular or cardiorenal hospitalization after 24 weeks of therapy.^{10 (link)} As 189 patients had data for this endpoint, the anchor value (mean value in each group indicating no treatment effect) was 95. Other secondary endpoints included change in 6MWD at 24 weeks and change in peak VO₂ and 6MWD after 12 weeks of therapy. Peak sildenafil levels at 12 and 24 weeks and coinciding plasma cGMP levels at 24 weeks were assessed. Using other pre-specified endpoints, we assessed the effect of PDE-5 inhibition on LV structure and vascular function by CMR, Doppler-estimated diastolic function parameters and pulmonary artery systolic pressure (PASP), and biomarkers that reflect renal and neuroendocrine function, oxidative stress and collagen metabolism.
The percent-predicted peak VO₂, 6MWD, and the presence of chronotropic incompetence and LVH were calculated using published criteria (e-Methods).^{11 (link)–14 (link)}