Ralinepag Phase II Open-Label Extension Study in Patients with Pulmonary Arterial Hypertension.

Introduction: Ralinepag is a potent, titratable, orally administered prostacyclin (IP) receptor agonist to treat pulmonary arterial hypertension. A phase II randomized, double-blind, parallel-group, placebo-controlled, 22-week study of immediate-release (IR) ralinepag safety and efficacy met its primary endpoint, significantly reducing pulmonary vascular resistance (PVR) compared with placebo. This phase II open-label extension (OLE) study assessed long-term safety and tolerability of ralinepag.

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.

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.

Efficacy and safety of riociguat in combination therapy for patients with pulmonary arterial hypertension (PATENT studies).

Many patients with pulmonary arterial hypertension do not achieve treatment goals with monotherapy, and therefore combination therapy is becoming the standard of care. The soluble guanylate cyclase stimulator riociguat is licensed for the treatment of pulmonary arterial hypertension; here we present findings from patients who were receiving combined riociguat plus endothelin receptor antagonists or non-intravenous prostanoids in the randomized, placebo-controlled PATENT-1 study and its open-label extension (PATENT-2). Moreover, we include new data from patients receiving early sequential combination therapy (three to six months of endothelin receptor antagonist treatment) or long-term background endothelin receptor antagonist therapy (>6 months).

Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial.

Background: Ambrisentan has shown effectiveness in the treatment of Group 1 pulmonary arterial hypertension (PAH). Although portopulmonary hypertension (PoPH) is a subset of Group 1 PAH, few clinical trials have been testing PAH therapies in patients with PoPH. The objective of this study is to evaluate the efficacy and safety of ambrisentan in PoPH.

Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial.

Purpose: This phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH).

Methods: 61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 μg twice daily.

Riociguat improves health-related quality of life for patients with pulmonary arterial hypertension: results from the phase 4 MOTION study.

Pulmonary arterial hypertension (PAH) is characterized by progressive dyspnea and exercise limitation and is associated with reduced health-related quality of life. Few clinical studies have evaluated the primary effects of treatment of PAH from the patient perspective. Here, we present the impact of riociguat on patient-reported outcomes (PROs) in treatment-naïve patients with PAH.

Mortality in Patients With Pulmonary Arterial Hypertension Treated With Continuous Prostanoids.

Background: Parenteral prostanoids are considered the treatment of choice for patients with severe pulmonary arterial hypertension (PAH). Prognostic studies for patients treated in the modern era are limited.

Methods: In this retrospective cohort study, patients initiating IV epoprostenol or IV or subcutaneous (SC) treprostinil therapy for PAH from 2007 to 2016 at UT Southwestern and The Ohio State University were included.

Quality of life and psychological symptoms in patients with pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) has a delay in diagnosis that makes time since diagnosis of interest in this population.

Objectives: To assess psychological conditions, perceived stress, QOL, and interpersonal support and to explore whether these factors may correlate with time since diagnosis in patients with PAH.

Methods: Participants at an academic medical center (n = 108) completed psychological questionnaires (Cambridge Pulmonary Hypertension Outcome Review, Patient Health Questionnaire-9, Perceived Stress Scale-10, and Interpersonal Support Evaluation List-Short Form).

Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.

Recommendations for the clinical management of patients receiving macitentan for pulmonary arterial hypertension (PAH): A Delphi consensus document.

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited.

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report.

Background: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.

Methods: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.

Results: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C).

Macitentan for the treatment of pulmonary arterial hypertension.

Introduction: Pulmonary arterial hypertension (PAH) is a serious disease characterized by elevation of pulmonary artery pressures and right ventricular failure. It is a progressive disease with a poor 5-year survival despite recent advances in treatment. Endothelin plays an important role in the development and progression of the disease.

Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report.

Objective: Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence.

Methods: This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases.

An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease.

Background: In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality.

Methods: A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations.

Managing an acutely ill patient with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by a vasculopathy that results in sustained elevation of pulmonary artery pressures, which ultimately leads to right ventricular failure (RVF) and death. Several advances have been made in the treatment of PAH, but it remains a major cause of morbidity and mortality. Managing an acutely ill patient with PAH is especially challenging.

Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies.

Doppler-defined pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with 40% mortality at 40 months. To assess the effect of bosentan in SCD-PH, two randomized, double-blind, placebo-controlled, 16-week studies were initiated. Safety concerns are particularly relevant in SCD due to comorbid conditions.

Community-acquired methicillin-resistant Staphylococcus aureus epidural abscess with bacteremia and multiple lung abscesses: case report.

A systemic infection due to community-acquired methicillin-resistant Staphylococcus aureus occurred in a hospital-naive 17-year-old girl with no history of soft-tissue infection. Although the initial signs and symptoms were indolent, systemic manifestations occurred, including extensive lung parenchymal damage and acute respiratory distress syndrome. The patient required long-term mechanical ventilation and was given linezolid for 8 weeks.

Development of a triage protocol for patients presenting with gastrointestinal hemorrhage: a prospective cohort study.

Introduction: Many patients presenting with acute gastrointestinal hemorrhage (GIH) are admitted to the intensive care unit (ICU) for monitoring. A simple triage protocol based upon validated risk factors could decrease ICU utilization.

Methods: Records of 188 patients admitted with GIH from the emergency department (ED) were reviewed for BLEED criteria (visualized red blood, systolic blood pressure below 100 mm Hg, elevated prothrombin time [PT], erratic mental status, and unstable comorbid disease) and complication within the first 24 hours of admission.