US commercial health plan coverage dynamics in pulmonary arterial hypertension therapies.

Background: Health plan coverage is central to patient access to care, especially for rare, chronic diseases. For specialty drugs, coverage varies, resulting in barriers to access. Pulmonary arterial hypertension (PAH) is a rare, progressive, and fatal disease.

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers.

IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension.

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. nhaled Iatinib ulmonary rterial ypertension linical rial (IMPAHCT; NCT05036135) is a phase 2b/3, randomized, double-blind, placebo-controlled, dose-ranging, and confirmatory study. IMPAHCT is designed to identify an optimal AV-101 dose (phase 2b primary endpoint: pulmonary vascular resistance) and assess the efficacy (phase 3 primary endpoint: 6-min walk distance), safety, and tolerability of AV-101 dose levels in subjects with pulmonary arterial hypertension using background therapies.

Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry).

Background: Selexipag is an oral prostacyclin receptor agonist, indicated for pulmonary arterial hypertension to delay disease progression and reduce the risk of pulmonary arterial hypertension-related hospitalization. SelexiPag: tHe usErs dRug rEgistry (NCT03278002) was a US-based, prospective, real-world registry of selexipag-treated patients.

Methods: Adults with pulmonary hypertension (enrolled 2016-2020) prescribed selexipag were followed for ≤18 months, with data collected at routine clinic visits.

Characteristics of patients with pulmonary arterial hypertension from an innovative, comprehensive real-world patient data repository.

Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease. PAH registries provide real-world data that complement clinical trial data and inform treatment decisions. The TRIO comprehensive, integrated patient data repository (TRIO CIPDR), is an innovative US repository capturing data on contemporary patients diagnosed with pulmonary hypertension and receiving US Food and Drug Administration-approved PAH therapies.

Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry.

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders.

AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study.

Background: Oral imatinib has been shown to be effective, but poorly tolerated, in patients with advanced pulmonary arterial hypertension (PAH). To maintain efficacy while improving tolerability, AV-101, a dry powder inhaled formulation of imatinib, was developed to deliver imatinib directly to the lungs.

Methods: This phase 1, placebo-controlled, randomised single ascending dose (SAD) and multiple ascending dose (MAD) study evaluated the safety/tolerability and pharmacokinetics of AV-101 in healthy adults.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Palliative care referrals in patients with pulmonary arterial hypertension: The Pulmonary Hypertension Association Registry.

Background: Pulmonary arterial hypertension (PAH) is a life limiting disease with substantial symptom burden and healthcare utilization. Palliative care alleviates physical and emotional symptoms for patients with serious illness, and has been underutilized for these patients.

Objective: To characterize patients with PAH referred to palliative care and identify predictors of referral.

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

Background: Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH.

Prediction of patient outcomes through social determinants of health: The Pulmonary Hypertension Association Registry (PHAR) evaluation.

Outcomes of patients with pulmonary arterial hypertension (PAH) may be associated with social determinants of health (SDOH) and other baseline patient characteristics. At present, there is no prognostic model to predict important patient outcomes in PAH based on SDOH. Utilizing information from the Pulmonary Hypertension Association Registry (PHAR), we derive a model (PHAR Evaluation or PHARE) to predict an important composite patient outcomes based on SDOH and other patient characteristics.

Delphi consensus recommendation for optimization of pulmonary hypertension therapy focusing on switching from a phosphodiesterase 5 inhibitor to riociguat.

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined.

Mortality in Pulmonary Arterial Hypertension in the Modern Era: Early Insights From the Pulmonary Hypertension Association Registry.

Background Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935).

CT Appearance of Pulmonary Arteriovenous Malformations and Mimics.

A pulmonary arteriovenous malformation (PAVM) is a fistulous connection between a pulmonary artery and a pulmonary vein that bypasses the normal pulmonary capillary bed resulting in a right-to-left shunt. Because of the potential for paradoxical emboli, PAVMs are treated when their feeding arteries exceed 3 mm or patients are symptomatic. PAVMs are often encountered in patients with suspected hereditary hemorrhagic telangiectasia (HHT).

Endothelial FGF signaling is protective in hypoxia-induced pulmonary hypertension.

Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in patients with PH and in mice exposed to chronic hypoxia. Endothelial FGFR1/2 signaling is important for the adaptive response to several injury types and we hypothesized that endothelial FGFR1/2 signaling would protect against hypoxia-induced PH.

Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: an analysis of the Pulmonary Hypertension Association Registry.

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization.

The Prognostic Value of Right Atrial Strain Imaging in Patients with Precapillary Pulmonary Hypertension.

Background: Right ventricular (RV) failure in patients with pulmonary hypertension (PH) is associated with unfavorable clinical events and a poor prognosis. Elevation of right atrial (RA) pressure is established as a marker for RV failure. However, the additive prognostic value of RA mechanical function is unclear.

Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE.

Background: Selexipag is a selective oral prostacyclin receptor agonist indicated for pulmonary arterial hypertension (PAH) treatment. SelexiPag: tHe usErs dRug rEgistry (SPHERE) (NCT03278002) is collecting data from selexipag-treated patients in real-world clinical practice to elucidate and describe the clinical characteristics, outcomes, and dosing/titration regimens of patients treated with selexipag in routine clinical practice.

Methods: SPHERE is a United States (US)-based, ongoing, multicenter, prospective observational study (target N = 800).

Reducing rates of readmission and development of an outpatient management plan in pulmonary hypertension: lessons from congestive heart failure management.

Pulmonary hypertension currently has minimal guidelines for outpatient disease management. Congestive heart failure studies, however, have shown effectiveness of disease management plans in reducing all-cause mortality and all-cause and congestive heart failure-related hospital readmissions. Heart failure exacerbation is a common reason for readmission in both pulmonary hypertension and congestive heart failure.

An expert panel delphi consensus statement on patient selection and management for transitioning between oral and inhaled treprostinil.

Treprostinil, a prostacyclin analogue used in the treatment of pulmonary arterial hypertension (PAH), is available for administration by parenteral, oral, or inhaled routes. Transitioning between routes may be beneficial for appropriate patients; however, there is little published data on transitions between oral and inhaled treprostinil. We used a modified Delphi process to develop expert consensus recommendations on transitions between these formulations.

EmPHasis-10 as a measure of health-related quality of life in pulmonary arterial hypertension: data from PHAR.

Introduction: While the performance of the emPHasis-10 (e10) score has been evaluated against limited patient characteristics within the United Kingdom, there is an unmet need for exploring the performance of the e10 score among pulmonary arterial hypertension (PAH) patients in the United States.

Methods: Using the Pulmonary Hypertension Association Registry, we evaluated relationships between the e10 score and demographic, functional, haemodynamic and additional clinical characteristics at baseline and over time. Furthermore, we derived a minimally important difference (MID) estimate for the e10 score.

Riociguat: Clinical research and evolving role in therapy.

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as an inhibitor of cGMP metabolism.

Residence at moderately high altitude and its relationship with WHO Group 1 pulmonary arterial hypertension symptom severity and clinical characteristics: the Pulmonary Hypertension Association Registry.

Background: WHO Group 1 pulmonary arterial hypertension is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression.