Macitentan and phosphodiesterase-5 inhibitor alone or in combination in newly diagnosed pulmonary arterial hypertension: a pooled analysis
Abstract
INTRODUCTION: Upfront combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i) is guideline-recommended for low- or intermediate-risk pulmonary arterial hypertension (PAH). This study compared time to all-cause mortality for macitentan+PDE5i combination and each monotherapy.
METHODS: Long-term patient-level data (planned follow-up ≥1 year) were pooled from four clinical trials and three observational registries. All-cause mortality data were available from adults with incident PAH initiated on macitentan 10 mg or PDE5i monotherapy, or macitentan+PDE5i. Propensity-score (PS) methods balanced key demographic and disease characteristics across cohorts. Hazard ratios (HRs) were computed from a Cox-regression model that included PS-calculated weights. Weighted Kaplan-Meier estimates with 95% confidence intervals (CI) were computed 6-monthly.
RESULTS: 2201 patients were included: 754 received macitentan+PDE5i (421 tadalafil, 324 sildenafil, 9 other), 654 macitentan, and 793 PDE5i (301 tadalafil, 490 sildenafil, 2 other). After weighting, characteristics were similar across cohorts. Upfront macitentan+PDE5i was associated with a 39% risk reduction of all-cause mortality versus PDE5i (HR 0.61 [95% CI 0.46-0.82]) and 32% versus macitentan (HR 0.68 [95% CI 0.37-0.95]). Reduction in all-cause mortality was 49% for macitentan+tadalafil vs tadalafil (HR 0.51 [95% CI 0.30-0.85]), 43% for macitentan+tadalafil vs macitentan (HR 0.57 [95% CI…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 2,201 participants or records.
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