Predictors of response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension

In pulmonary arterial hypertension (PAH), achieving low risk profile or improving risk score after initial treatment is related with good prognosis, although this favorable response is unpredictable. Objective: Identify parameters that might predict the effect of phosphodiesterase-5 inhibitors (PDE5i) on risk profile in PAH. Methods: We analyzed patients from the Spanish Registry (REHAP) followed for ≥1 yrs after initiating PDE5i treatment as mono- or add-on therapy, between July 2007-Sep 2019. Initial combination therapy was excluded. Treatment responders were considered when at 12 months met 3 criteria: 1) alive; 2) no clinical events leading to treatment change; 3) improved ESC/ERS risk score or remained in low-risk. Results: 763 patients were analyzed: 213 responders and 431 non-responders (85 died, 197 required treatment change, 149 risk score worsened or remained intermediate/high). 119 patients lacking data on risk stratification were excluded. Proportion of naïve, prevalent cases and hemodynamic severity at diagnosis were similar in both groups. Responders were younger (49±16 vs 55±16 years, p<0.001), more frequently male (41% vs 30%, p=0.01) and in low-risk at baseline (44% vs 17%, p<0.0001). At baseline, responders were more often in FC I-II (60% vs 26%, p<0.0001), covered longer 6-min walk distance (436±117 vs 356±119 m, p<0.0001), had higher DLCO% (57±19 vs 49±23, p<0.01) and lower NT-proBNP (1127±2981 vs 2220±2786 pg/mL, p=0.002). Idiopathic PAH was more common in non-responders (33% vs 25%, p<0.05). Conclusion: Older women, with iPAH and worse risk profile at baseline is associated with a less favorable effect of PDE5i on risk profile. Funded by an unrestricted grant from MSD.