Prognosis and Treatment With Phosphodiesterase 5 Inhibitors in Combined Post‐ and Precapillary Pulmonary Hypertension: A Propensity Score‐Matched Analysis From the Hellenic Pulmonary Hypertension Registry

Combined post- and precapillary pulmonary hypertension (CpcPH) comprises the most severe form of postcapillary PH. A severe precapillary component (pulmonary vascular resistance [PVR] > 5 WU) is critical for therapeutic decisions. Current treatment guidelines focus on optimizing underlying cardiac disease, while there are conflicting data regarding the efficacy and safety of pulmonary arterial hypertension (PAH) drugs in selected patients. This study examines the impact of PVR > 5 WU on survival in heart failure with preserved ejection fraction (HFpEF) and CpcPH and evaluates the effect of treatment with phosphodiesterase 5 inhibitors (PDE5is) on clinical and hemodynamic parameters and on prognosis. The Hellenic Pulmonary Hypertension Registry (HOPE) enrolls patients from all PH groups in Greece. This study focuses on Group 2 CpcPH patients with HFpEF. Propensity score matching was performed to reduce the risk of bias in the treatment selection and potential confounders. Kaplan-Meier curve was used to estimate 5-year survival, and the log-rank test was used for the comparisons. A total of 98 patients were included, with a median follow-up of 2.9 years. PVR > 5 WU and age were independently associated with worse survival ([HR 2.15, 95% CI 1.13-4.83, <i>p</i> = 0.04], [HR 1.07, 95% CI 1.03-1.13, <i>p</i> = 0.003], respectively). Propensity-matched cohort analysis indicated that PDE5i treatment was associated with a significant reduction in PVR at follow-up (from median [IQR] 4.89 [1.9] WU to 3.1 [2.0] WU, <i>p</i> = 0.04) and a trend towards improved survival. Severe precapillary component is associated with impaired prognosis in CpcPH. While PDE5i treatment shows promise in improving hemodynamic outcomes, its effect on long-term survival requires further investigation.