Abstract
Purpose: Elevated SCr associates with poor outcome in PAH. We retrospectively analyzed the effect of SIL on SCr in PAH patients (pts) from SUPER-1 and -2 studies. SCr relationships with 6-min walk distance (6MWD), functional class (FC), time to clinical worsening (TTCW), and survival were examined.
Methods: PAH pts received placebo (PBO) or SIL 20, 40, or 80 mg TID in SUPER-1 and open-label SIL titrated to 80 mg TID (as tolerated) in SUPER-2. SCr, 6MWD, FC, and TTCW were assessed at baseline (BL) and wk 12 in SUPER-1; survival was tracked for 3 y in SUPER-2. Analysis of covariance (treatment as a factor; BL value as covariate) assessed SCr change from BL to wk 12 (posthoc). Relationships between SCr and ≥10% 6MWD increase and ≥1-class FC improvement (using logistic regression) and TTCW and survival (Cox regression) were assessed.
Results: BL characteristics were similar among groups (N=277); PAH was mostly idiopathic (63%) and FC II (39%) or III (58%). SCr increased at wk 12 vs BL with PBO (0.032 mg/dL) and decreased with SIL (–0.001, –0.035, and –0.048 mg/dL for 20, 40, and 80 mg TID, respectively); the difference vs PBO with 80 mg TID was significant (P=0.032). SCr reduction was associated with improved 6MWD (OR 4.74; 95% CI, 1.07–21.05; P=0.04) and FC (OR 6.64; 95% CI, 1.37–32.16; P=0.019). Pts with higher SCr had higher risk of worsening (HR 44.38; 95% CI, 6.67–295.32; P<0.0001) and a trend toward higher risk of mortality (HR 2.62; 95% CI, 0.22–30.55; P=0.44).
Conclusion: In posthoc analysis, sildenafil dose-dependently decreased SCr in PAH pts; reduced SCr was associated with improved 6MWD and FC and reduced risk of clinical worsening.
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