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. Guidelines suggest starting or rapidly escalating to combination therapy with drugs of differing classes (phosphodiesterase 5 inhibitors [PDE5is], soluble guanylate cyclase stimulators [sGC stimulators], endothelin receptor antagonists [ERAs], and prostacyclin pathway agents [PPAs]). OBJECTIVE: To assess the variation in commercial health plan coverage for PAH treatments and how coverage has evolved. To examine the frequency of coverage updates and evidence cited in plan policies. METHODS: We used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes publicly available specialty drug coverage policies. Overall, and at the drug and treatment class level, we identified plan-imposed coverage restrictions beyond the drug's US Food and Drug Administration label, including step therapy protocols, clinical restrictions (eg, disease severity), and prescriber specialty requirements. We analyzed variation in coverage restrictiveness and how coverage has changed over time. We determined how often plans update their policies. Finally, we categorized the cited evidence into 6 different types. RESULTS: Results reflected plan coverage policies for 13 PAH drugs active between August 2017 and August 2022 and issued by 17 large US commercial health plans, representing 70% of covered lives. Coverage restrictions varied mainly by step therapy protocols and prescriber restrictions. Seven plans had step therapy protocols for most drugs, 9 for at least one drug, and 1 had none. Ten plans required specialist (cardiologist or pulmonologist) prescribing for at least one drug, and 7 did not. Coverage restrictions increased over time: the proportion of policies with at least 1 restriction increased from 38% to 73%, and the proportion with step therapy protocols increased from 29% to 46%, with generics as the most common step. The proportion of policies with step therapy protocols increased for every therapy class with generic availability: 18% to 59% for ERAs, 33% to 77% for PDE5is, and 33% to 43% for PPAs. The proportion of policies with prescriber requirements increased from 24% to 48%. Plans updated their policies 58% of the time annually and most often cited the 2019 CHEST clinical guidelines, followed by randomized controlled trials. CONCLUSIONS: Plan use of coverage restrictions for PAH therapies increased over time and varied across both drugs and plans. Inconsistency among health plans may complicate patient access and reduce the proportion who can persist on PAH treatments.

Impact of selexipag use within 12 months of pulmonary arterial hypertension diagnosis on hospitalizations and medical costs: A retrospective cohort study.

BACKGROUND: Oral selexipag, a prostacyclin pathway agent (PPA), is effective in patients with pulmonary arterial hypertension (PAH). The objective of this study is to assess the impact of initiating oral selexipag within 12 months of diagnosis on health outcomes. METHODS: This retrospective cohort study used data from Optum's de-identified Clinformatics® Data Mart Database. PAH patients between 1 October 2015 and 30 September 2019 were included. Patients were also required to have received PAH medication within 12 months of their initial diagnosis. Study groups included patients who initiated selexipag within 12 months of PAH diagnosis (SEL ≤ 12) and those who did not initiate any PPA within 12 months of PAH diagnosis (No PPA ≤ 12). Inverse probability of treatment weighting was used to remove potential confounding between groups. Cox and Poisson regression models were used to compare hospitalization and disease progression. Generalized linear model with gamma distribution and log link was used to compare costs. RESULTS: SEL ≤ 12 had lower rate of all-cause hospitalizations (rate ratio: 0.76, 95% confidence interval [CI]: 0.60, 0.96) versus no PPA ≤ 12, but no differences in PAH-related hospitalization rate (rate ratio: 1.03, 95% CI: 0.79, 1.33) or risk of disease progression (hazard ratio: 1.01, 95% CI: 0.71, 1.44). SEL ≤ 12 incurred lower all-cause (mean difference: -$23 623; 95% CI: -35 537, -8512) and PAH-related total medical costs (mean difference: -$12 927; 95% CI: -19 559, -5679) versus no PPA ≤ 12. CONCLUSION: Selexipag initiation within 12 months of PAH diagnosis demonstrated reductions in all-cause hospitalization rate and medical costs.

Cost-utility of ambrisentan and bosentan for pediatric pulmonary arterial hypertension.

INTRODUCTION: Despite the increasing evidence supporting the efficacy of ambrisentan and bosentan in improving functional classes among pediatric patients with pulmonary arterial hypertension (PAH), there is a lack of information regarding their cost implications. Therefore, the objective of this study is to assess the cost-utility of bosentan compared to ambrisentan for the treatment of pediatric patients with PAH in Colombia. METHODS: We employed a Markov model to estimate the costs and quality-adjusted life-years (QALYs) associated with the use of ambrisentan or bosentan in pediatric patients diagnosed with pulmonary arterial hypertension (PAH). To ensure the reliability of our findings, we conducted sensitivity analyses to assess the robustness of the model. In our cost-effectiveness analysis, we evaluated the outcomes at a willingness-to-pay (WTP) threshold of US$5,180. RESULTS: The expected annual cost per patient receiving ambrisentan was estimated to be $16,055 (95% CI 15,937 -16,172), while for bosentan it was $14,503 (95% CI 14,489 -14,615). The QALYs per person estimated for ambrisentan were 0.39 (95% CI 0.381-0.382), whereas for bosentan it was 0.40 (95% CI 0.401-0.403). CONCLUSION: Our economic evaluation shows that ambrisentan is not cost-effective regarding bosentan to in treating pulmonary arterial hypertension in C.

Predicting Risk of 1-Year Hospitalization Among Patients with Pulmonary Arterial Hypertension.

INTRODUCTION: US claims-based analyses emphasize the substantial hospitalization burden of patients with pulmonary arterial hypertension (PAH) and the significant need for improved monitoring and more timely interventions. A claims-based predictive model may be useful to assist healthcare providers and payers in identifying patients with PAH at increased hospitalization risk. To address this aim, we constructed statistical models using baseline patient variables available in administrative healthcare claims to predict patients' risk for all-cause and PH-related hospitalization within 1 year of initiating ≥ 1 PAH indicated medication. METHODS: Adult patients with PAH who newly initiated ≥ 1 PAH indicated medication were selected from the MarketScan Commercial and Medicare Supplemental databases (January 1, 2009-January 31, 2019). Cox regression models were built with a randomly selected training set and evaluated using a validation set of remaining patients. Predictive variables for the models were selected in three steps: clinical knowledge, univariate analysis, and backward stepwise selection. RESULTS: Within 1 year of initiating ≥ 1 PAH indicated medication, 1502/3872 (38.8%) had an all-cause hospitalization and 950/3872 (24.5%) had a pulmonary hypertension (PH)-related hospitalization. Predictive risk factors for all-cause hospitalization were Quan-Charlson Comorbidity Index (CCI) score 2-3 [hazard ratio (HR) 1.229; P = 0.038] and ≥ 4 (HR 1.531; P < 0.001), claims-based frailty index (CFI) score > 1 (highest frailty level; HR 1.301; P = 0.018), hemoptysis (HR 1.254; P = 0.016), malaise/fatigue (HR 1.150; P = 0.037), history of PH-related hospitalization (HR 1.171; P = 0.011), non-PH-related ER visit (HR 1.713; P = 0.014), and higher non-PH-related outpatient visit cost (HR 1.069; P < 0.001). Predictive risk factors for PH-related hospitalization were female sex (HR 1.264; P = 0.004), Quan-CCI score ≥ 4 (HR 1.408; P = 0.008), portal hypertension (HR 1.565; P = 0.019), CFI score > 1 (HR 1.522; P = 0.002), dyspnea (HR 1.259; P = 0.023), and history of PH-related hospitalization (HR 1.273; P = 0.002). CONCLUSIONS: The US claims-based predictive models showed acceptable performance to predict 1-year hospitalization among patients with PAH.

Comparative evaluation of costs and healthcare resource utilization of oral selexipag versus inhaled treprostinil or oral treprostinil in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), a rare vasculopathy progressively leading to right heart failure and death, is associated with considerable economic burden. Oral prostacyclin pathway agents (PPAs) like selexipag and treprostinil address an underlying PAH pathway, yet are often under-utilized. Data on head-to-head cost comparison of various PPAs is lacking. METHODS: In this retrospective study using a large health claims database, we compared the per-patient-per-year (PPPY) costs and healthcare resource utilization (HRU) among PAH patients taking either oral selexipag, inhaled treprostinil or oral treprostinil in the United States between July 2015 and March 2020. Patients with ≥1 prescription for one of the drugs of interest, ≥1 in-patient pulmonary hypertension (PH) diagnosis, or ≥ 2 outpatient PH diagnoses were included in this study. Baseline differences between the three groups were adjusted using an inverse probability of treatment weighting approach. 411 patients were selected for the final study cohorts. RESULTS: All-cause hospitalization costs were highest for oral treprostinil ($39,983) compared to oral selexipag ($20,635) and inhaled treprostinil ($16,548; p = .037). Total PAH-related medical costs were 40% lower for patients on oral selexipag compared to patients on oral and inhaled treprostinil ($24,351 vs. $40,398 and $40,339, respectively; p = .006). PAH-related outpatient visits were lowest for patients on oral selexipag (14 PPPY visits) compared to oral treprostinil (16 PPPY visits) and inhaled treprostinil (22 PPPY visits; p = .001). CONCLUSIONS: Compared to oral and inhaled treprostinil, oral selexipag may incur lower medical costs and reduce PAH related outpatient visits for patients with PAH.

Ambrisentan for in pediatric pulmonary arterial hypertension: A cost-utility analysis.

INTRODUCTION: Despite the growing evidence of efficacy, little is known regarding the efficiency of ambrisentan to decrease cost and improve the functional classes of pediatric patients with pulmonary arterial hypertension. This study aims to determine the cost-utility of ambrisentan regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. METHODS: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of ambrisentan, or sildenafil in pediatric patients with pulmonary arterial hypertension. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The base-case analysis showed that compared with sildenafil, ambrisentan was associated with higher costs and higher QALYs. The expected annual cost per patient with ambrisentan was US$16,105 and with sildenafil was US$1431. The QALYs per person estimated with ambrisentan was 0.40 and for sildenafil was 0.39. The estimated improvement in quality of life and reduced costs results in an estimate of economic dominance for sildenafil over ambrisentan. CONCLUSION: Our economic evaluation shows that ambrisentan is not cost-effective regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Assessment of Inhaled Treprostinil Palmitil, Inhaled and Intravenous Treprostinil, and Oral Selexipag in a Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension.

Treprostinil palmitil (TP), a long-acting inhaled pulmonary vasodilator prodrug of treprostinil (TRE), has beneficial effects in a Sugen5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) that compare favorably to the oral phosphodiesterase 5 inhibitor (PDE5) sildenafil. In this study in male Sprague-Dawley rats, a dry powder formulation of TP (TPIP) was compared with inhaled and intravenous TRE and oral selexipag to evaluate inhibition of hemodynamic and pathologic changes in the lungs and heart induced by Su/Hx challenge. Su (20 mg/kg) was injected subcutaneously followed by 3 weeks of Hx (10% O2/balance N2) and then initiation of test article administration over 5 weeks with room air breathing. Hemodynamics and histopathology were measured at the end of the study. Su/Hx challenge approximately doubled the mean pulmonary arterial blood pressure (mPAP) and the Fulton index, decreased cardiac output (CO), doubled the wall thickness and muscularization of the small (10-50 µm) and medium (51-100 µm) sized pulmonary arteries, and increased the percentage of obliterated pulmonary blood vessels. Even though inhaled TRE (65 µg/kg, 4× daily), intravenous TRE (810 ng/kg/min), and oral selexipag (30 mg/kg, twice daily) provided some beneficial effects against the Su/Hx challenge, the overall benefit was generally greater with TPIP at high dose (117 µg/kg, once daily). These results demonstrate that TPIP compares favorably to inhaled and intravenous TRE and oral selexipag with respect to inhibition of the pathophysiological changes induced by Su/Hx challenge in rats. SIGNIFICANCE STATEMENT: Treprostinil palmitil (TP) is a long-acting pulmonary vasodilator prodrug of treprostinil (TRE) formulated for inhaled administration by dry powder [treprostinil palmitil inhalation powder (TPIP)]. Comparison of the activity of TPIP, inhaled and intravenous TRE, and oral selexipag in a Sugen5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension demonstrated that each of these drugs exert protection against the hemodynamic and histopathological changes induced by the Su/Hx challenge, with the greatest effect on these changes produced by TPIP.

Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model.

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, there is no cure for PAH. It is important to discover new compounds that can be used to treat PAH. The mouse hypoxia-induced PAH model is a widely used model for PAH research. This model recapitulates human clinical manifestations of PAH Group 3 disease and is an important research tool to evaluate the effectiveness of new experimental therapies for PAH. Research using this model often requires the administration of compounds in mice. For a compound that needs to be given directly into the bloodstream, optimizing intravenous (IV) administration is a key part of the experimental procedures. Ideally, the IV injection system should permit multiple injections over a set time course. Although the mouse hypoxia-induced PAH model is very popular in many laboratories, it is technically challenging to perform multiple IV bolus dosing and invasive hemodynamic assessment in this model. In this protocol, we present step-by-step instructions on how to carry out multiple IV bolus dosing via mouse jugular vein and perform arterial and right ventricle catheterization for hemodynamic assessment in mouse hypoxia-induced PAH model.

Indirect treatment comparison and cost-minimization analysis of riociguat versus selexipag in patients with pulmonary arterial hypertension.

OBJECTIVES: The comparative efficacy between riociguat and selexipag in patients with pulmonary arterial hypertension (PAH) has never been described in literature. Our aim was to prepare indirect treatment comparison (ITC) to evaluate the cost-effectiveness of riociguat in Czechia. METHODS: A systematic literature review identified two relevant trials with comparable endpoints to inform a Bucher ITC of relative and absolute effects. Given the comparable efficacy of riociguat and selexipag, a cost-minimization analysis (CMA) was conducted. RESULTS: A Bucher ITC provided evidence for the comparable relative efficacy of riociguat defined as the odds of unimproved functional class III 0.761 (95% CI 0.372 to 1.558; p = 0.455) compared to selexipag and a comparable absolute efficacy defined as a difference in the 6-minute walking distance of 10.560 meters (95% CI -10.692 to 31.812; p = 0.330). The CMA identified riociguat as the cost-saving therapy. CONCLUSIONS: Switching to riociguat represents the cost-saving therapy for PAH patients who were inadequately compensated with the PDE5i+ERA therapy. Consequently, riociguat has been introduced to the list of reimbursed medicines in Czechia from October 2021. Based on two global trials, we prepared the first indirect treatment comparison followed with CMA of these therapies that may improve future decision-making for PAH indications.

The Clinical and Cost Utility of Cardiac Catheterizations in Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: To evaluate the cost-utility of catheterization-obligate treatment in preterm infants with pulmonary hypertension, as compared with empiric initiation of sildenafil based on echocardiographic findings alone. STUDY DESIGN: A Markov state transition model was constructed to simulate the clinical scenario of a preterm infant with echocardiographic evidence of pulmonary hypertension associated with bronchopulmonary dysplasia (BPD) and without congenital heart disease under consideration for the initiation of pulmonary vasodilator therapy via one of two modeled treatment strategies-empiric or catheterization-obligate. Transitional probabilities, costs and utilities were extracted from the literature. Forecast quality-adjusted life-years was the metric for strategy effectiveness. Sensitivity analyses for each variable were performed. A 1000-patient Monte Carlo microsimulation was used to test the durability of our findings. RESULTS: The catheterization-obligate strategy resulted in an increased cost of $10 778 and 0.02 fewer quality-adjusted life-years compared with the empiric treatment strategy. Empiric treatment remained the more cost-effective paradigm across all scenarios modeled through one-way sensitivity analyses and the Monte Carlo microsimulation (cost-effective in 98% of cases). CONCLUSIONS: Empiric treatment with sildenafil in infants with pulmonary hypertension associated with BPD is a superior strategy with both decreased costs and increased effectiveness when compared with catheterization-obligate treatment. These findings suggest that foregoing catheterization before the initiation of sildenafil is a reasonable strategy in preterm infants with uncomplicated pulmonary hypertension associated with BPD.

Development and evaluation of a predictive algorithm for unsatisfactory response among patients with pulmonary arterial hypertension using health insurance claims data.

OBJECTIVE: This study aimed to develop and validate a predictive algorithm for unsatisfactory response to initial pulmonary arterial hypertension (PAH) therapy using health insurance claims. METHODS: Adult patients with PAH initiated on a first PAH therapy (index date) were identified from Optum's de-identified Clinformatics Data Mart Database (1/1/2010-12/31/2019). A random survival forest algorithm was developed using patient-month data and predicted the "survival function" (i.e. risk of not having unsatisfactory response) over time. For each patient-month observation, risk factors were assessed in the 12 months prior. Unsatisfactory response was defined as the first instance of (1) new PAH therapy, (2) PAH-related hospitalization or emergency room visit, (3) lung transplant or atrial septostomy, (4) PAH-related death or (5) chronic oxygen therapy initiation. To facilitate use in clinical practice, a simplified risk score was also developed based on a linear combination of the most important risk factors identified in the algorithm. RESULTS: In total, 4781 patients were included (median age = 69.0 years; 58.6% female). Over a median follow-up of 14.0 months, 3169 (66.3%) had an unsatisfactory response. The most important risk factors included in the algorithm were healthcare resource use (i.e. PAH-related outpatient visits, pulmonologist visits, cardiologist visits, all-cause hospitalizations), time since first PAH diagnosis, time since index date, Charlson Comorbidity Index, dyspnea, and age. Predictive accuracy was good for the full algorithm (C-statistic: 0.732) but was slightly lower for the simplified risk score (C-statistic: 0.668). CONCLUSION: The present claims-based algorithm performed well in predicting time to unsatisfactory response following initial PAH therapy.

Riociguate para o tratamento da hipertensão pulmonar tromboembólica crônica (HPTEC) inoperável, persistente ou recorrente após tratamento cirúrgico / Riociguate for the treatment of hypertension chronic pulmonary thromboembolism (CTEPH) inoperable, persistent or recurrent after surgical treatment

INTRODUÇÃO: Este Relatório tem como objetivo analisar as evidências apresentadas pelo demandante acerca de eficácia, segurança, custo-efetividade e impacto orçamentário do riociguate para o tratamento de hipertensão pulmonar tromboembólica crônica (HPTEC) inoperável ou persistente/recorrente em adultos com vistas à incorporação ao Sistema Único de Saúde (SUS). A hipertensão pulmonar (HP) corresponde a um grupo de condições clínicas que se apresentam como elevação anormal da pressão na circulação pulmonar. Conforme o VI Simpósio Mundial de Hipertensão Pulmonar, a definição de HP incluiu uma medida de pressão arterial pulmonar média (PAPm) > 20 mmHg que, juntamente com outros critérios, definirão o grau da HP 1,2 . A HPTEC é um subtipo de hipertensão pulmonar pertencente ao Grupo 4. Tratase de uma doença debilitante independentemente da faixa etária dos pacientes, levando a dependência de cuidados. Dada sua incidência, essa doença também é classificada como rara3,4 . A HPTEC é definida como a persistência de trombos organizados n

Relatório de recomendação final para adoção de um protocolo estadual no estado de Santa Catarina complementar ao protocolo clínico e diretrizes terapêuticas do ministério da saúde para tratamento farmacológico da hipertensão pulmonar no âmbito do SUS / Final recommendation report for the adoption of a state protocol in the state of Santa Catarina complementary to the clinical protocol and therapeutic guidelines of the Ministry of Health for pharmacological treatment of pulmonary hypertension within the scope of the SUS

Este relatório refere-se à análise crítica do documento "Diagnóstico e Tratamento de Hipertensão Pulmonar'', elaborado pela ACAPTI e enviado como proposta para elaboração de Protocolo Estadual de Hipertensão Pulmonar, contemplando o tratamento farmacológico de HP grupo 1 (HAP) e grupo 4 (HPTEC). No documento encaminhado pelo demandante consta uma breve introdução e contextualização da patologia, diagnóstico clínico e exames complementares, critérios de inclusão e exclusão, especialidades médicas, estratificação de risco e seguimento, tratamento medicamentoso, algoritmo de tratamento medicamentoso, acessos aos medicamentos e centros de referência. Os itens relacionados ao diagnóstico foram mantidos neste relatório, conforme o documento enviado pelo demandante. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização do medicamento Selexipague, a disponibilização da terapia combinada (Ambrisentana, Bosentana, Sildenafila, Ilopros a e Selexipague) para o tratamento da HP grupo 1 (HAP), a disponibilização do medicamento Riociguate para tratamento de HP grupo 4 (HPTEC), algoritmo de tratamento medicamentoso e fluxo de acesso aos medicamentos, para posterior elaboração de um Protocolo Estadual para a patologia solicitada. O Protocolo Estadual será elaborado complementarmente ao protocolo do Ministério da Saúde, assim, caso os medicamentos englobados nele sejam incorporados para a patologia em questão pela CONITEC, o fornecimento dos mesmos passa a ser por meio do CEAF.

Short-term Cost Comparison of Systemic Heparin Therapy vs. Catheter Directed Thrombolysis for the Treatment of Massive and Submassive Pulmonary Embolism with Long-Term Chronic Pulmonary Hypertension Cost Model.

INTRODUCTION: Pulmonary embolism (PE) is a significant disease process that affects an estimated 117 cases per 100,000 person-years. Chronic pulmonary hypertension (CPH) is a long-term complication associated with acute PE which has a significant cost to treat, ranging from $98,000-117,000. METHODS: A retrospective chart review of 341 patients from January 2011 to November 2018 who presented with massive or submassive PE and were treated with either systemic heparin therapy or catheter directed thrombolysis (CDT). The results of the short-term cost analysis and pulmonary hypertension rates from data collected was then used in a long-term cost model using a standardized 100 patient model. RESULTS: Treatment with CDT resulted in fewer bleeding complications (4.2 percent vs. 13.8 percent, p=0.005), a shorter length of stay, a greater percentage of patients returning to their prior living conditions (89.0 percent vs. 79.3 percent, p=0.042), and a lower rate of chronic pulmonary hypertension at 12 months (6.3 percent vs. 15.9 percent, p=0.030) than those treated with systemic heparin. The expense of treatment utilizing CDT was greater than those undergoing systemic heparin treatment with a difference of approximately $31,000 (p=0.001) though our cost model showed the heparin group to have a higher cost over time. CONCLUSIONS: For patients with massive or submassive PE, this study demonstrated a significant long-term cost savings and improved outcomes for patients treated with catheter directed thrombolysis when compared to systemic heparin administration.

Systematic review and cost-effectiveness of bosentan and sildenafil as therapeutic drugs for pediatric pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease in children, with significant mortality. Because of the limited research on pediatric PAH, first, systematic review of related drugs is conducted, and then economic evaluation of PAH drug treatment programs is conducted, which to provide a reference for the choice of more cost-effective treatment options. METHODS: The search includes electronic databases such as Pubmed, ScienceDirect, and Embase. Through inclusion and exclusion criteria, screen high-quality randomized controlled trials. We used TreeAge Pro 2011 software to construct the markov model, that to simulate the total medical cost and quality-adjusted life years (QALYs), and to calculate the incremental cost-effectiveness ratio. Sensitivity analysis of transfer probability, utility, and cost was carried out. RESULTS: Incorporate two studies that meet the criteria, one compared the therapeutic effects of bosentan and placebo on pediatric PAH, the other compared therapeutic effects of sildenafil and placebo on pediatric PAH, both articles were of good quality. Compared with the sildenafil group (3.38QALYs and $161,120.14), the QALY of the bosentan treatment group (3.33QALYs and $257,411.29) was reduced by 0.05, and the cost increased by $96,291.15. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for sildenafil over bosentan. This dominant result persisted probabilistic analyses. CONCLUSIONS: Based on this model, a more cost-effective treatment drug for PAH in children is sildenafil.

Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions.

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.