Systemic sclerosis–associated PAH: staying on initial therapy linked to better survival

Design

Retrospective analysis of the EUSTAR registry

Population

301 treatment-naive patients with systemic sclerosis–associated PAH, 2000–2021

Primary outcome

All-cause mortality and 36-month PAH progression

Effect

As-treated mortality HR 0.50 (mono) and 0.40 (combination); ITT no association

This EUSTAR registry analysis included 301 treatment-naive patients with systemic sclerosis–associated pulmonary arterial hypertension meeting the 2022 haemodynamic definition (mean PAP above 20 mmHg). Two-thirds started therapy within four months of right heart catheterisation.

Only 31% of patients with milder haemodynamics (mPAP 21–24 mmHg and/or PVR 2–3 WU) were treated, against 79% of those meeting the older definition. Combination therapy rose from 14% to 67% across low- to high-risk groups. Over a median 3.9 years, 42% died. In the primary as-treated analysis, sustained monotherapy (HR 0.50, 95% CI 0.27–0.92) and combination therapy (HR 0.40, 0.18–0.88) were associated with lower mortality, and sustained initial therapy with less progression (HR 0.37). The intention-to-treat analysis, however, showed no association.

The gap between the two analyses is the key caveat — people who stay on therapy may be healthier. But the low treatment rate in milder disease, despite the revised definition, suggests patients may be under-treated, and the signal supports trials of earlier treatment.

• Apply the 2022 haemodynamic definition (mPAP above 20 mmHg) when interpreting right heart catheter results.
• Discuss patients with milder haemodynamics at a PAH centre rather than defaulting to observation.
• Use risk stratification to guide initial monotherapy versus combination therapy.
• Support adherence and monitor tolerance; sustained therapy was associated with better outcomes.
• Recognise this is observational; the intention-to-treat analysis showed no benefit.

Why it matters

The revised PAH definition widened who could be treated, but practice has not followed in milder disease.

Don't overread it

Observational; the benefit appeared only in as-treated analyses, which are prone to bias.

The statistics, in plain English

As-treated analysis compares patients by what they actually took; intention-to-treat by what they started. When the first shows benefit and the second does not, the difference may come from who stays on treatment rather than from the treatment itself.

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