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.

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.

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.

Efficacy and safety of sotatercept across ranges of cardiac index in patients with pulmonary arterial hypertension: A pooled analysis of PULSAR and STELLAR.

Background: This analysis examined the effects of the activin signaling inhibitor, sotatercept, in pulmonary arterial hypertension (PAH) subgroups stratified by baseline cardiac index (CI).

Methods: Pooled data from PULSAR (N = 106; NCT03496207) and STELLAR (N = 323; NCT04576988) were analyzed using 2 different CI thresholds, <2.0 and ≥2.

Heart Failure Among Asian American Subpopulations.

Importance: Heart failure (HF) is a leading cause of death in the US. The current evidence on the burdens of HF in Asian American populations, especially Asian American subgroups, is limited and inconsistent.

Objective: To assess and compare the incidence and prevalence of HF in Asian American subgroups.

Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus.

Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy.

Clinical trial design, end-points, and emerging therapies in pulmonary arterial hypertension.

Clinical trials in pulmonary arterial hypertension (PAH) have led to the approval of several effective treatments that improve symptoms, exercise capacity and clinical outcomes. In phase 3 clinical trials, primary end-points must reflect how a patient "feels, functions or survives". In a rare disease like PAH, with an ever-growing number of treatment options and numerous candidate therapies being studied, future clinical trials are now faced with challenges related to sample size requirements, efficiency and demonstration of incremental benefit on traditional end-points in patients receiving background therapy with multiple drugs.

Computational platform for doctor-artificial intelligence cooperation in pulmonary arterial hypertension prognostication: a pilot study.

Background: Pulmonary arterial hypertension (PAH) is a heterogeneous and complex pulmonary vascular disease associated with substantial morbidity. Machine-learning algorithms (used in many PAH risk calculators) can combine established parameters with thousands of circulating biomarkers to optimise PAH prognostication, but these approaches do not offer the clinician insight into what parameters drove the prognosis. The approach proposed in this study diverges from other contemporary phenotyping methods by identifying patient-specific parameters driving clinical risk.

Derivation of a Risk Score (REVEAL-ECHO) Based on Echocardiographic Parameters of Patients With Pulmonary Arterial Hypertension.

Background: Multiparametric risk assessment tools determine mortality risk in patients with pulmonary arterial hypertension (PAH) by combining invasive and noninvasive variables so management strategies can be tailored to individuals.

Research Question: Can a risk score based on common echocardiographic parameters risk-stratify patients with PAH?

Study Design And Methods: A Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) echocardiographic risk score (REVEAL-ECHO) was derived using retrospective echocardiographic data from 2,400 adult patients with PAH enrolled in the REVEAL registry database. A stepwise Cox regression model identified echocardiographic parameters significantly predictive of survival.

The evolving landscape of pulmonary arterial hypertension clinical trials.

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects.

Contemporary risk scores predict clinical worsening in pulmonary arterial hypertension - An analysis of FREEDOM-EV.

Background: Risk scores integrate clinical variables emphasizing symptoms, exercise capacity, and measures of cardiac strain to predict clinical outcome better than any single value in pulmonary arterial hypertension (PAH). Risk scores have demonstrated prognostic utility for outcomes in registries, and recent studies have suggested that they are also therapy-responsive in controlled trials.

Methods: FREEDOM-EV, a global, placebo-controlled, event-driven study, randomized 690 PAH participants 1:1 to oral treprostinil (TRE) or placebo.