PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR). PAH associated with connective tissue disease (CTD) has poorer outcomes compared with other etiologies. Therapies (including sildenafil) improved physical functioning (PF) and hemodynamics (including PVR) in randomized trials. The relationship between PVR and changes in PF is not fully characterized.
METHODS: Two double-blind trials in adult PAH patients compared placebo with sildenafil, alone (12-week study) or added to epoprostenol therapy (16-week study). The Short Form (SF)-36 assessed 8 domains, including PF. Differences between baseline and end-of-study PVR and SF-36 PF measurements were assessed using an analysis of covariance model (with baseline score as a covariate). Pearson correlation coefficients described SF-36 PF and PVR relationships.
RESULTS: In the 12-week study, mean PVR change (dyn•s•cm-5) from baseline was greater for sildenafil-treated vs placebo-treated patients (-180± 333 vs 49±368; P< 0.0001) overall and in PAH-CTD (-181±258 vs -19±157; P=0.03). Mean SF-36 PF score change from baseline was higher for sildenafil-treated vs placebo-treated patients (13.7±19.5 vs 4.5±16.0; P< 0.0001) overall and in PAH-CTD (10.7±17.4 vs 2.9±18.4; P=0.04). Correlations (95% CI) between changes in SF-36 PF and PVR were -0.19 (-0.32, -0.05) for all (n=198) and -0.19 (-0.42, 0.07) for PAH-CTD (n=61). In the 16-week study, mean PVR change was significant for sildenafil vs placebo (-175±270 vs 3±176; P< 0.0001), but not for PAH-CTD (-77±229 vs 39±138; P=0.10). Mean SF-36 PF change was significant for sildenafil vs placebo (10.8±21.5 vs 2.7±20.9; P< 0.01), but not for PAH-CTD (1.8±18.9 vs -1.2±20.7; P=0.50). Correlations (95% CI) were -0.21 (-0.35, -0.06) for all (n=166) and 0.05 (-0.29, 0.38) for PAH-CTD (n=34).
CONCLUSION: Changes in SF-36 PF score and PVR were greater for sildenafil than placebo in adult PAH patients, including those with PAH-CTD; however, these variables showed low correlation.
CLINICAL IMPLICATIONS: Sildenafil improved SF-36 physical functioning and PVR in adults with PAH. Low correlation between these variables necessitates research to identify variables that explain or predict physical functioning.
DISCLOSURE: Marko Mychaskiw, Employee All authors are employees of Pfizer Inc.; No Product/Research Disclosure Information