Background/Purpose: Pulmonary arterial hypertension (PAH) is a leading cause of death in patients with systemic sclerosis (SSc).  Although survival has improved with PAH-specific medications in the last decade, the optimal therapy remains unknown.  We sought to compare the one year outcome of SSc-PAH patients with different therapeutic classes of PAH-specific medications. 

Methods:

Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) is a multi-center prospective registry of SSc patients at high risk for PAH or with definite PH diagnosed by right heart catheterization (RHC) within 6 months of enrollment.  To be included in this analysis, patients had to have World Health Organization (WHO) Group I PAH, and have received a PAH-specific medication for > 3 months duration.   We assessed patient outcomes for four therapeutic classes: endothelin receptor antagonists (ERA), phosphdiesterase type 5 inhibitors (PDE-5), prostacyclins (PCA) and those started immediately on combination therapy (≥2 of the other classes).  A Kaplan-Meier curve was estimated for 1 year survival from the time the PAH treatment was started, and differences between the drug classes were assessed by the log-rank test.   Rates of hospitalizations at one year were compared by chi-square tests.   

Results: In the PHAROS registry 160 individuals have PAH, of whom 120 either had≥ 1 year of follow-up or had died prior to 1year of follow-up.  Of these, 101 had been treated with a PAH medication for > 3 months and comprised the analysis population.  The mean age was 59.0 ± 10.4 years, 85% were female, 80% Caucasian and 11% African-American.  67% were classified as limited cutaneous SSc.  Overall, initial therapy was a PDE-5 in 47%, ERA in 30%, PCA in 13% and combination therapy in 10%.  In the PCA group 85% started inhaled, and 15% started parental therapy.   With those with a baseline NYHA class within two months of therapy initiation, 25% of the PCA group were class IV, as compared to 20% in the combination, 0% ERA and 7% PDE5.   At one year 7% (n=7) on medications had died, whereas 10% had died at one year in the entire PHAROS cohort.  There was a statistically significant difference between the drug classes with 98% of PDE-5, 97% of ERA, 69% of PCA and 90% of combination therapy alive at one year (p=0.002).   At one year 28% of patients had been hospitalized, but there was no difference in rate of all-cause hospitalization (p=0.78) or PAH-related hospitalizations (p=0.91) between the drug classes.   Similarly, there was no difference in progression to combination therapy with 27% of PDE5, 23% of ERA and 13% of PCA (p=0.67).   

Conclusion: At one year there is no difference in rates of hospitalization or progression to combination drug therapy among the PAH-specific drug classes.  However, there was a difference in one-year survival between the drug classes, with those started on PCAs clearly having the lowest survival.   This may reflect that those patients had more severe pulmonary vascular disease at baseline.  Further follow-up is needed to determine whether long-term outcomes differ between the PAH therapeutic drug classes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/survival-hospitalization-or-need-for-combination-therapy-at-one-year-in-patients-with-scleroderma-associated-pulmonary-arterial-hypertension/