Sustained therapy associated with better outcomes in systemic sclerosis–associated pulmonary arterial hypertension

An observational EUSTAR analysis examined initial treatment and outcomes in 301 treatment-naïve patients with systemic sclerosis–associated pulmonary arterial hypertension (SSc-PAH), identified during 2000–2021 and meeting the 2022 haemodynamic definition. Initial therapy was defined as treatment started within four months of right heart catheterisation. Outcomes were all-cause mortality and PAH progression within 36 months; as-treated analyses were primary and intention-to-treat analyses supportive.

Overall, 198 patients (66%) initiated therapy, and 170 maintained it for at least three months. Treatment initiation was less frequent in patients with milder haemodynamic impairment—mean pulmonary arterial pressure 21–24 mmHg and/or pulmonary vascular resistance 2–3 Wood units—than in those meeting the previous definition (31% versus 79%). Combination therapy increased from 14% in low-risk patients to 67% in high-risk patients. During median follow-up of 3.9 years, 125 patients (42%) died; 85 of 227 (37%) experienced progression.

Adjusted as-treated analyses associated sustained monotherapy and combination therapy with lower mortality (hazard ratios 0.50, 95% CI 0.27–0.92, and 0.40, 95% CI 0.18–0.88, respectively). Sustained initial therapy was associated with lower progression risk (HR 0.37, 95% CI 0.18–0.76). However, adjusted intention-to-treat analyses found no association with either outcome. These contrasting estimates limit causal interpretation of the observational findings. Mortality estimates in the milder subgroup were imprecise, supporting dedicated prospective studies rather than definitive treatment conclusions.