Predicting Response to Switching From Phosphodiesterase Type 5 Inhibitor to Riociguat in Patients With Pulmonary Arterial Hypertension: Biomarker and Responder Analysis of the RESPITE and REPLACE Studies.

This exploratory analysis assessed whether plasma biomarkers predict the response to switching from phosphodiesterase type 5 inhibitors (PDE5is) to the soluble guanylate cyclase stimulator riociguat in patients with pulmonary arterial hypertension. Selected biomarkers at baseline and their changes to Week 24 were evaluated in patients with and without a favorable response to riociguat in two trials: RESPITE, in which patients with an inadequate response to PDE5i were switched to riociguat; and REPLACE, in which patients at intermediate risk of 1-year mortality despite a PDE5i were randomized to remain on PDE5i or were switched to riociguat. A response was defined as absence of clinical worsening and at least two of the following criteria: 6-min walk distance increase by 10% or ≥ 30 m, World Health Organization functional class I/II, or -terminal prohormone of brain natriuretic peptide reduction of ≥ 30% at Week 24.

Hemodynamics and Phosphodiesterase-5 Inhibitor Treatment Associated with Survival in ILD-PH: A PVRI GoDeep Meta-Registry Analysis.

Background: Pulmonary hypertension (PH) in interstitial lung disease (ILD) lacks approved therapies. The PVRI GoDeep meta-registry collects real-world data of PH patients from international PH referral centers.

Methods: ILD-PH patients and relevant subgroups (IIP, IPF) were stratified by pulmonary vascular resistance (PVR).

Long-Term Mortality and Morbidity Impact on Patients with Pulmonary Arterial Hypertension (PAH) If Access to Sotatercept Is Delayed: A Simulation Model.

Introduction: Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT, where BGT included mono-, double-, or triple-PAH targeted therapy. Building on the trial's findings, a population health model was recently published assessing the long-term clinical impact of sotatercept.

Withdrawal of prostacyclin pathway therapies after initiation of sotatercept treatment in patients with pulmonary arterial hypertension.

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Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death.

Background: Sotatercept improves exercise capacity and delays the time to clinical worsening in patients with World Health Organization (WHO) functional class II or III pulmonary arterial hypertension. The effects of add-on sotatercept in patients with advanced pulmonary arterial hypertension and a high risk of death are unclear.

Methods: In this phase 3 trial, we randomly assigned patients with pulmonary arterial hypertension (WHO functional class III or IV) and a high 1-year risk of death (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score, ≥9) who were receiving the maximum tolerated dose of background therapy to receive add-on sotatercept (starting dose, 0.

Pathogenic SMAD6 variants in patients with idiopathic and complex congenital heart disease associated pulmonary arterial hypertension.

In patients with complex congenital heart disease (CHD) pathogenic SMAD6 variants have been described previously. The aim of this study was to analyze if pathogenic SMAD6 variants also occur in patients with CHD associated with pulmonary arterial hypertension (CHD-APAH) or idiopathic PAH. A PAH gene panel with up to 64 genes including SMAD6 was used to sequence 311 patients with idiopathic PAH (IPAH) and 32 with CHD-APAH.

Mono and combination therapies in pulmonary arterial hypertension patients with comorbidities: A COMPERA analysis.

Aims: Pulmonary arterial hypertension (PAH) is often diagnosed in elderly patients with comorbidities. Although initial monotherapy is recommended for these patients, the value of combination therapy remains unclear. Here, we compare the efficacy of initial monotherapy and combination therapy in PAH patients with cardiovascular comorbidities.

Consistent Safety and Efficacy of Sotatercept for Pulmonary Arterial Hypertension in Mutation Carriers and Noncarriers: A Planned Analysis of a Phase II, Double-Blind, Placebo-controlled Clinical Trial (PULSAR).

It is unclear whether carriers of pathogenic variants in PAH-associated genes have a distinct response to PAH treatment. To evaluate the effect of genetic variant status on the efficacy of sotatercept and the effect of sotatercept treatment on biomarkers in pulmonary arterial hypertension. PULSAR (A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension; NCT03496207) was a phase II, randomized controlled study of sotatercept versus placebo added to background therapy for pulmonary arterial hypertension.

Outcomes in Patients Receiving Treatment for Pulmonary Arterial Hypertension Associated With Repaired Congenital Heart Disease.

Background: Pulmonary arterial hypertension (PAH) is a common complication among patients with congenital heart disease (CHD). Despite advances in PAH treatment, evidence for the benefits of PAH therapies in CHD-PAH is limited.

Objectives: This analysis aimed to evaluate outcomes in patients with repaired PAH-CHD receiving an approved PAH drug.

Future treatment paradigms in pulmonary arterial hypertension: a personal view from physicians, health authorities, and patients.

Novel treatments in pulmonary arterial hypertension (PAH) with significant pathophysiological and clinical responses have generated renewed interest in changing the course of the disease and achieving long-term disease control. Historically, the term disease modification was coined in rheumatological conditions with therapies that managed to treat the underlying condition as opposed to just alleviating symptoms. With the advent of novel therapies, the term disease modification was introduced in our discussions.

A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA.

Background: SOTERIA (ClinicalTrials.gov: NCT04796337) is an ongoing open-label study evaluating long-term safety, tolerability and efficacy of sotatercept in participants with pulmonary arterial hypertension (PAH).

Methods: Eligible adults with PAH on stable background therapy who completed a prior sotatercept study without early discontinuation were enrolled.

Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies.

Introduction: Pulmonary arterial hypertension is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways.

Methods: This , exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies.

Reassessing Pulmonary Hypertension Classification: Utilizing Criteria for Heart Failure with Preserved Ejection Fraction Instead of Pulmonary Arterial Wedge Pressure.

: The current classification of pulmonary hypertension (PH) distinguishes between pre-capillary (PAWP ≤ 15 mmHg) and post-capillary (PAWP > 15 mmHg) forms, with left heart disease, especially heart failure with preserved ejection fraction (HFpEF), being a common cause of PH. We investigated the suitability of an HFpEF diagnosis instead of PAWP in diagnosing PH associated with HFpEF. : In a retrospective, single-center analysis, we reviewed diagnoses from our database, focusing on patients initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) or PH associated with HFpEF (PH-HFpEF) based on their PAWP.

Riociguat in pulmonary arterial hypertension: Application of the 4-strata COMPERA 2.0 risk assessment tool in the PATENT studies.

Background: Risk stratification is an essential part of evaluating disease severity in patients with pulmonary arterial hypertension (PAH). This study applied the 4-strata COMPERA 2.0 risk model to the Phase 3 PATENT-1/2 studies of riociguat.