Beyond Risk Scores: Translating PAH Risk Assessment into Clinical Benefit. Comment on Cortes-Telles et al. Sequential Add-On Therapy Modifies Mortality Risk Stratification in Group 1.4 Pulmonary Arterial Hypertension: A Real-World, Single-Center Retrospective Cohort Study from Mexico. J. Clin. Med. 2026, 15, 4924

Q: What is the clinical evidence from this study?

Study design: Editorial. Population: Group 1.4 pulmonary arterial hypertension (PAH) (n=25). Intervention: Sequential add-on therapy with macitentan and sildenafil. Primary outcome: Proportion of patients classified as low risk according to COMPERA 2.0.

Q: What does this research mean for the field?

Sequential add-on therapy with macitentan and sildenafil increases the proportion of Group 1.4 pulmonary arterial hypertension patients classified as low risk from 19% to 43% according to COMPERA 2.0 at 24 weeks. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ilma Nascimento; Caio Júlio César dos Santos Fernandes

doi:10.3390/jcm15186969

September 9, 2026Journal of Clinical MedicineOpen Access

Beyond Risk Scores: Translating PAH Risk Assessment into Clinical Benefit. Comment on Cortes-Telles et al. Sequential Add-On Therapy Modifies Mortality Risk Stratification in Group 1.4 Pulmonary Arterial Hypertension: A Real-World, Single-Center Retrospective Cohort Study from Mexico. J. Clin. Med. 2026, 15, 4924

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Why the study?

Does sequential add-on therapy with macitentan and sildenafil improve risk classification in patients with Group 1.4 pulmonary arterial hypertension?

Key Points

Evaluate how sequential add-on medical therapy alters mortality risk stratification in Group 1.4 pulmonary arterial hypertension and assess the real-world feasibility of risk-guided care.
Retrospective cohort study analyzing N=25 patients with Group 1.4 pulmonary arterial hypertension treated at a single referral center in Mexico.
Patients received sequential add-on therapy with macitentan and sildenafil over a 24-week follow-up period.
Risk stratification was evaluated using COMPERA 2.0 and REVEAL Lite 2 tools alongside functional capacity, biomarkers, and right ventricular echocardiographic metrics.
After 24 weeks, the proportion of patients classified as low risk increased from 19% to 43% according to COMPERA 2.0 and from 40% to 68% according to REVEAL Lite 2.
Brain natriuretic peptide levels and World Health Organization functional class improved, while the 6 min walk distance remained essentially unchanged and the TAPSE/systolic pulmonary artery pressure ratio did not improve significantly.
Intermittent drug shortages were documented during follow-up, demonstrating that theoretical treatment escalation does not ensure continuous drug access in resource-constrained settings.

Structured PICO

Does sequential add-on therapy with macitentan and sildenafil improve risk classification in patients with Group 1.4 pulmonary arterial hypertension?

P

Population

25 patients with Group 1.4 pulmonary arterial hypertension treated at a referral center in Mexico, followed for 24 weeks.

E

Exposure

Sequential add-on therapy with macitentan and sildenafil

O

Outcome

Change in risk classification (proportion of patients classified as low risk according to COMPERA 2.0 and REVEAL Lite 2) at 24 weekssurrogate

Main Result

Absolute Event Rate: 43% vs 19%

Limitations

Intermittent drug shortages limited continuous treatment access and longer-term follow-up
Resource-constrained setting

Implication

This editorial highlights that while sequential add-on therapy can improve risk scores in PAH, translating these improvements into clinical benefit requires consistent medication access and healthcare system capacity.

Abstract

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Cite This Study

Nascimento et al. (2026) conducted an editorial in Group 1.4 pulmonary arterial hypertension (PAH) (n=25). Sequential add-on therapy with macitentan and sildenafil was evaluated on Proportion of patients classified as low risk according to COMPERA 2.0.

synapsesocial.com/papers/6aa269eaa1e750260650a01f https://doi.org/10.3390/jcm15186969

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Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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