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. 2025 May 12;15(2):e70099.
doi: 10.1002/pul2.70099. eCollection 2025 Apr.

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

Georgios E Papadopoulos  1 , Alexandra Arvanitaki  1 , Sophia-Anastasia Mouratoglou  1 , Panagiotis Gourgiotis  1 , Thomas Chrysochoidis-Trantas  1 , Athena Mpatsouli  2 , Aris Bechlioulis  3 , Aikaterini Naka  3 , Eftychia Demerouti  4 , Panagiotis Karyofyllis  4 , Dimitrios Tsiapras  4 , Anastasia Anthi  2 , Athanasios Manginas  5 , Antonios Ziakas  1 , Stephan Rosenkranz  6 , George Giannakoulas  1
Affiliations

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

Georgios E Papadopoulos et al. Pulm Circ. .

Abstract

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, p = 0.04], [HR 1.07, 95% CI 1.03-1.13, p = 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, p = 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.

Keywords: heart failure with preserved ejection fraction; phosphodiesterase 5 inhibitors; pulmonary hypertension; pulmonary vascular resistance; survival.

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Conflict of interest statement

G.G. has received fees for lectures and/or consultations from Actelion/Janssen, Bayer, Boehringer‐Ingelheim, ELPEN Pharmaceuticals, Ferrer‐Galenica, GlaxoSmithKline, Gossamer‐Bio, MSD, Pfizer, Lilly, and United Therapeutics. A.N. has received minor support via the University of Ioannina for participation in RCTs, advisory boards, and lecture fees from Amgen, Astra, Bayer, BMS, Boehringer Ingelheim, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier, and has also received Horizon2020 funding for the CardioCare project. E.D. and P.K. received honorarium and consultation fees from Actelion Pharmaceuticals‐Janssen Hellas, MSD Merck Hellas, Elpen, and Galenica. D.T. has received in the past travel awards from Actelion/Janssen. A.M. has served on advisory boards for AstraZeneca, Bayer, Elpen, Janssen, MSD, and Novartis. S.R. has received fees for lectures and/or consultations from Abbott, Acceleron, Actelion, Aerovate, AOP, AstraZeneca, Bayer, Boehringer‐Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, and United Therapeutics. His institution has received research grants from Actelion, AstraZeneca, Bayer, Janssen, and Lempo. G.E.P., A.A., S.‐A.M., P.G., T.C.‐T., A.M., A.B., A.A., and A.Z. declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study's flow chart. Abbreviations: HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IpcPH, isolated postcapillary pulmonary hypertension; PDE5i, phosphodiesterase 5 inhibitor; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; WU, woods units.
Figure 2
Figure 2
Survival analysis of CpcPH patients' overall cohort. Abbreviation: CpcPH, combined post‐ and precapillary pulmonary hypertension.
Figure 3
Figure 3
Survival analysis of CpcPH patients in different PVR groups. Red dashed line: overall survival. Abbreviations: CpcPH, combined post‐ and precapillary pulmonary hypertension; PVR, pulmonary vascular resistance; WU, woods units.
Figure 4
Figure 4
Changes in functional and hemodynamic status of CpcPH patients treated with PDE5is. Abbreviations: 6‐MWD, six‐minute walking distance; NT‐proBNP, N‐terminal‐pro‐brain natriuretic peptide; PVR, pulmonary vascular resistance.
Figure 5
Figure 5
Survival analysis of the matched cohort of CpcPH patients depending on the treatment group. Abbreviations: CpcPH, combined post‐ and precapillary pulmonary hypertension; PDE5i, phosphodiesterase 5 inhibitor.
See this image and copyright information in PMC

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