Predictors of the Response to Phosphodiesterase-5 Inhibitors in Pulmonary Arterial Hypertension: an Analysis of the Spanish Registry

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2023 Sep 15

PMID 37715261

Authors

Agustin R Garcia

Isabel Blanco

Lluis Ramon

Jesus Perez-Sagredo

Francisco J Guerra-Ramos

Clara Martin-Ontiyuelo

Olga Tura-Ceide

Francisco Pastor-Perez

Pilar Escribano-Subias

Joan A Barbera

Affiliations

Soon will be listed here.

Abstract

Background: Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients.

Objective: To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH.

Methods: We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response.

Results: Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response.

Conclusion: Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies.

Citing Articles

Differential drug response in pulmonary arterial hypertension: The potential for precision medicine.

Miller E, Sampson C, Desai A, Karnes J Pulm Circ. 2023; 13(4):e12304.

PMID: 37927610 PMC: 10621006. DOI: 10.1002/pul2.12304.

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