Intravenous Prostanoids in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

A Single-Centre Experience

Maria Vlachou; Hossam Fayed; Adele Dawson; Sally Reddecliffe; Alexander Stevenson; Ross J Thomson; Benjamin Emmanuel Schreiber; J. Gerry Coghlan


Rheumatology. 2022;61(3):1106-1114. 

In This Article

Abstract and Introduction


Objectives: The current study evaluates survival rates among SSc-associated pulmonary arterial hypertension (SSc-PAH) patients on i.v. prostanoids, and short-term impact of i.v. prostanoids on clinical and haemodynamic parameters.

Methods: Baseline demographics, invasive and non-invasive data, European Society of Cardiology (ESC) score and REVEAL score of 81 SSc-PAH patients (median age 61 years, interquartile range 54–67 years, 84% females) were prospectively recorded, from November 2006 till November 2020, before initiation of i.v. prostanoids, and at first formal reassessment. Survival data were retrieved from National Health Service Spine and hospital databases.

Results: Significant improvements in clinical and haemodynamic parameters in response to i.v. prostanoid therapy were documented. Functional class (FC) (16.6% improved by 1FC, P =0.041), mean pulmonary arterial pressure (−6.5 mmHg, P =0.036), pulmonary vascular resistance (−2.6 WU, P =0.012), cardiac index (Q/m2) (+0.7 l/min/m2, P =0.003) and mixed venous oxygen saturation (SvO2) (+3%, P =0.036) improved. Estimated survival for CTD-PAH patients on i.v. prostanoids was 64%, 31% and 18%, at 1 year, 3 years and 5 years, respectively. Independent baseline predictors of mortality were older age (HR: 1.043, 95% CI: 1.011–1.075, P =0.007), higher N-terminal pro-brain natriuretic peptide levels (HR: 2.191, 95% CI: 1.131–4.243, P =0.020), and lower SvO2 levels (HR: 0.962, 95% CI: 0.926–0.998, P =0.039). High ESC risk or high and very high REVEAL score was associated with significantly worse survival compared with patients with lower risk scores, both at baseline and when reassessed after a median of 6.5 months.

Conclusions: Survival among SSc-PAH patients on i.v. prostanoids remains poor, risk scoring at baseline and after 6.5 months of therapy improves prognostication.


Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary vasculature associated with progressive narrowing of the distal pulmonary arteries, leading to an inexorable rise in vascular resistance, increased right ventricular workload and ultimately to right heart failure and death.[1–3] The cause of this disorder remains unknown in most cases (idiopathic PAH, IPAH), where the driver is known congenital heart disease-associated PAH and CTD-associated PAH (CTD-PAH), while an increasing proportion is being identified as associated with genetic mutations (heritable PAH).[1,2]

Advances in orally administered treatments have been dramatic over the past 20 years, with substantial prognostic and clinical benefits being clearly demonstrated in IPAH and more recently in CTD-PAH, including systemic sclerosis-associated PAH (SSc-PAH), the dominant subgroup.[4,5]

Chronically administered i.v. epoprostenol was the first treatment shown to improve outcomes in PAH and remains the most effective treatment available.[1,6,7] While clinical benefit was demonstrated in patients with SSc-PAH, unlike IPAH, mortality benefit has not been demonstrated.[1,6–9]

Patients with SSc-PAH are generally much older than those with IPAH, have multisystem disease with lung and cardiac involvement, dexterity issues, and are more prone to pulmonary veno-occlusive disease (PVOD) – which may lead to pulmonary oedema when treated with prostanoids.[9–11] The decision to initiate i.v. prostanoid therapy in patients with CTD-PAH is necessarily more nuanced, and the limited published data on efficacy and tolerability may contribute to delayed escalation in treatment or non-compliance with guidelines.

The limited published data in the CTD-PAH population has not addressed the haemodynamic or serological response, nor the value of risk profiling in predicting outcome.[9,11–13] Further limited detail has been provided on the tolerability of treatment or the impact of PVOD, known to be prevalent in this population.[11,12]

We have evaluated the impact of i.v. prostanoid therapy in a contemporary cohort of SSc-PAH patients treated at the Royal Free Hospital to determine whether survival has indeed improved, whether risk scores at initiation of i.v. therapy and at first formal re-evaluation add value and we describe the tolerability of such treatment.