PT  - JOURNAL ARTICLE
AU  - Nazzareno Galie
AU  - Robyn Barst
AU  - Bruce Brundage
AU  - Hossein A. Ghofrani
AU  - Ronald Oudiz
AU  - Gerald Simonneau
TI  - Tadalafil in idiopathic or heritable pulmonary arterial hypertension compared to pulmonary arterial hypertension associated with connective tissue disease
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p2299
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p2299.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p2299.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Patients (pts) with PAH associated with connective tissue disease (APAH-CTD) have a worse prognosis compared to idiopathic (I) or heritable (H)PAH. Our objective was to evaluate the clinical outcomes in these two subgroups.In a 16 week (wk), double-blind, placebo (PBO) controlled trial with blinded 52 wk extension, pts were randomized to PBO, 20 or 40mg tadalafil (Tad) qd (APAH-CTD: n=16, 21 and 19, respectively; I/HPAH: n=54, 50 and 46, respectively); subgroup efficacy analyses included six-minute walk test (6MWT, 40mg) at Wk16 (assessed by rank permutation tests) and clinical worsening (CW, PBO and 40mg) at Wk16 and up to 68wks (20 and 40mg). Pts on 20mg without CW at 16wks remained on 20mg; all others received 40mg in the extension.Mean changes in 6MWT from baseline to Wk16 were 32m in APAH-CTD and 38m in I/HPAH for 40mg Tad dose. PBO-corrected treatment effects on 6MWT at Wk 16 were 49m in APAH-CTD (P=0.03) and 22m in I/HPAH (P=0.04). The% of pts with CW in the Tad 40mg and PBO subgroups at Wk16 were 11 and 25% in APAH-CTD, respectively; and 4 and 15% in I/HPAH, respectively. In pts who received Tad 20 or 40mg up to 68wks, CW was 35% in APAH-CTD (n=40) and 24% in I/HPAH (n=96).Tad 40mg improves 6MWT at Wk16 in APAH-CTD and I/HPAH; however, with PBO 6MWT decreased in APAH-CTD but not in I/HPAH pts. In addition, CW was numerically less with Tad in both subgroups at Wk16 compared to PBO. At Wk68, CW was numerically higher in APAH-CTD vs. I/HPAH. These latter data are consistent with a worse prognosis in APAH-CTD. Whether more aggressive therapy earlier in APAH-CTD pts would be efficacious requires further study.