- Design
- Multinational registry cohort (EUSTAR), as-treated and intention-to-treat analyses
- Population
- 301 treatment-naive patients with SSc-PAH
- Primary outcome
- All-cause mortality and 36-month PAH progression
- Effect
- As-treated mortality HR 0.50 (monotherapy), 0.40 (combination); ITT no association
A EUSTAR analysis studied 301 treatment-naive patients with systemic sclerosis-associated pulmonary arterial hypertension meeting the 2022 haemodynamic definition (2000–2021).
Two-thirds started therapy within four months of right heart catheterisation. Only 31% of those with milder haemodynamics (mean pulmonary pressure 21–24 mmHg and/or PVR 2–3 Wood units) were treated, against 79% of those meeting the older, stricter definition. Combination therapy rose from 14% in low-risk to 67% in high-risk patients. Over a median 3.9 years, 42% died. In as-treated analyses, sustained monotherapy (HR 0.50) and combination therapy (HR 0.40) were associated with lower mortality, and sustained therapy with less progression (HR 0.37). Intention-to-treat analyses showed no association.
The gap between analyses illustrates how hard it is to judge treatment effects from registries: patients who stay on therapy differ from those who stop. But the variation in who gets treated suggests implementation gaps, particularly under the newer, lower thresholds.
For rheumatologists, the practical point is to ensure catheter-confirmed PAH is discussed with a PAH centre promptly, including milder cases.
- Refer catheter-confirmed SSc-PAH to a pulmonary hypertension centre promptly.
- Do not dismiss milder haemodynamic abnormalities under the 2022 definition without specialist review.
- Support patients to continue initial PAH therapy beyond the first months.
- Risk-stratify at diagnosis, since combination therapy is used more in higher-risk patients.
Why it matters
The 2022 definition widened who has PAH, and fewer than a third of milder cases were treated.
Don't overread it
Benefit appeared only in as-treated analyses; intention-to-treat showed no association, so causation is uncertain.
The statistics, in plain English
As-treated analysis compares those who stayed on therapy with those who did not, which can favour treatment if healthier patients stay on drugs. Intention-to-treat analysis avoids that bias but here found no difference. The truth may lie between them.
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