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

Background: Dynamic risk stratification is fundamental to the modern management of pulmonary arterial hypertension (PAH). However, data on the impact of sequential add-on therapy in patients with Group 1.4 PAH—particularly in Latin American populations—remains limited. This study evaluated changes in risk classification using COMPERA 2.0 and REVEAL Lite 2 scores in patients treated with endothelin receptor antagonist (ERA) and phosphodiesterase type 5 inhibitor (PDE5i) combination therapy (macitentan + sildenafil) at a referral center in Mexico. Methods: In this single-center, retrospective cohort study, 25 patients with a confirmed diagnosis of PAH between 1st January 2022 and 31st December 2024 were evaluated at baseline and after 24 weeks of treatment. Clinical, functional, and biochemical parameters were recorded. Within-patient changes were analyzed using the Wilcoxon signed-rank test, and agreement between risk assessment tools was assessed using Spearman’s correlation coefficient. Results: At 24 weeks, patients demonstrated significant improvement in World Health Organization functional class (p = 0.002) and a significant reduction in brain natriuretic peptide levels (p = 0.003). Both COMPERA 2.0 and REVEAL Lite 2 scores showed a consistent shift toward lower-risk categories. A strong concordance between the two tools was observed. Conclusions: Sequential add-on ERA + PDE5i therapy was associated with meaningful improvement in risk stratification among patients with Group 1.4 PAH. These findings support the clinical utility of simplified, noninvasive risk assessment tools in real-world settings, particularly in resource-constrained environments.