Effectiveness, Safety, and Economic Comparison of Inhaled Epoprostenol Brands, Flolan and Veletri, in Acute Respiratory Distress Syndrome.

Background: No previous studies exist examining 2 inhaled epoprostenol formulations in an acute respiratory distress syndrome (ARDS) patient population. Objective: The study aim was to evaluate a formulary conversion from inhaled Flolan to Veletri to determine the impact on effectiveness, safety, and cost in patients with ARDS. Methods: This was a single-center, retrospective, matched cohort observational study at a tertiary care academic medical center. Patients included were mechanically ventilated, adult patients with ARDS receiving inhaled Flolan or Veletri for ≥1 hour in the intensive care unit. Results: A total of 132 patients were included in the matched cohort. There was no difference detected in change in partial pressure of arterial O2/fraction of inspired O2 (PaO2/FiO2) ratio after 1 hour of therapy between the inhaled Flolan and Veletri groups (27.2 ± 46.2 vs 30 ± 68 mm Hg, P = 0.78). Significant differences in secondary outcomes included incidence of hypotension (83% vs 95.5%, P = 0.04) and thrombocytopenia (9.1% vs 29.5%, P < 0.01) in the inhaled Flolan and Veletri groups, respectively, with no difference in cost per duration of therapy (P = 0.29). Conclusions and Relevance: There was no difference in the change in PaO2/FiO2 ratio after 1 hour of therapy between inhaled Flolan and Veletri in an ARDS patient population. The formulary conversion from inhaled Flolan to Veletri was likely justified.

Economic evaluation of sildenafil for the treatment of pulmonary arterial hypertension in Indonesia.

BACKGROUND: This study aims to assess the cost-effectiveness and budget impact of adopting sildenafil to the benefits package for the indication of pulmonary arterial hypertension (PAH), compared to beraprost. METHODS: Based on a societal perspective, a model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). RESULTS: The economic model calculated the incremental cost-effectiveness ratio (ICER) per QALY gained for using sildenafil as first-line therapy compared to beraprost for the patient in functional class (FC) II and III, i.e. USD 3098 and USD 2827, respectively. The results indicated that in spite of sildenafil being more expensive than beraprost, generic sildenafil could potentially be a good value for money since ICER per QALY is below one times gross domestic product (GDP) per capita in Indonesia. Furthermore, budget impact analysis estimated that the incremental budget needed within 5 years for including sildenafil compared to beraprost for PAH patients starting in FC II and FC III was USD 436,775 and USD 3.6 million, respectively. CONCLUSIONS: Compared to beraprost, sildenafil would be preferable for the treatment of PAH patients in FC II and FC III in Indonesia. The additional budget for adopting sildenafil compared to beraprost as the treatment of PAH in the benefits package was estimated at around USD 4.0 million.

Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review.

Objectives: Although many studies have reported on the cost-effectiveness of bosentan for treating pulmonary arterial hypertension (PAH), a systematic review of economic evaluations of bosentan is currently lacking. Objective evaluation of current pharmacoeconomic evidence can assist decision makers in determining the appropriate place in therapy of a new medication. Methods: Systematic literature searches were conducted in English-language databases (MEDLINE, EMBASE, EconLit databases, and the Cochrane Library) and Chinese-language databases (China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP) to identify studies assessing the cost-effectiveness of bosentan for PAH treatments. Results: A total of 8 published studies were selected for inclusion. Among them were two studies comparing bosentan with epoprostenol and treprostinil. Both results indicated that bosentan was more cost-effective than epoprostenol, while the results of bosentan and treprostinil were not consistent. Four studies compared bosentan with other endothelin receptor antagonists, which indicated ambrisentan might be the drug of choice for its economic advantages and improved safety profile. Only two economic evaluations provided data to compare bosentan versus sildenafil, and the results favored the use of sildenafil in PAH patients. Four studies compared bosentan with conventional, supportive, or palliative therapy, and whether bosentan was cost-effective was uncertain. Conclusions: Bosentan may represent a more cost-effective option compared with epoprostenol and conventional or palliative therapy. There was unanimous agreement that bosentan was not a cost-effective front-line therapy compared with sildenafil and other endothelin receptor antagonists. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.

Prostacyclin Use Among Patients with Pulmonary Arterial Hypertension in the United States: A Retrospective Analysis of a Large Health Care Claims Database.

BACKGROUND: Prostacyclins play an important role in the management of pulmonary arterial hypertension (PAH). Intravenous prostacyclin was the first disease-specific treatment for patients with PAH. Subcutaneous and nonparenteral (oral or inhaled) formulations have subsequently become available. However, data are lacking on how these different prostacyclin formulations are being used in clinical practice. OBJECTIVES: To (a) conduct retrospective analyses of a large U.S. health care claims database to describe the characteristics of patients with PAH initiating prostacyclin therapy, and (b) evaluate their treatment patterns, health care resource use, and associated costs. METHODS: Truven Commercial and Medicare databases were used to define annual cohorts of adults with PAH between January 1, 2010, and October 31, 2015. These patients were identified based on claims with ICD-9-CM diagnoses indicative of PAH (codes 416.0 or 416.8) and claims for PAH-specific medications and PAH-related procedures. Patients with evidence of receiving a prostacyclin were identified, and prostacyclin use was categorized as parenteral versus nonparenteral. Health care costs were assessed alternatively employing an all-cause and PAH-related perspective. RESULTS: Of 13,633 adults with identified PAH, 3,006 (22.0%) received a prostacyclin during at least 1 year of the study period, and annual prevalence of prostacyclin use ranged from 19.9% to 22.6%. Across calendar years, the median age of prostacyclin users ranged from 56 to 58 years, and 71.9%-75.8% were female. Among prostacyclin users, parenteral prostacyclin use declined from 63.2% in 2010 to 46.5% in 2015, while use of nonparenteral prostacyclins increased from 39.7% to 56.2% over the same period (both P < 0.001). Few patients (2.7%-4.1%) received both parenteral and nonparenteral formulations in a given calendar year. Among patients using prostacyclins, receipt of other PAH-specific medications increased from 62.1% in 2010 to 79.2% in 2015. Comparing the 6 months preceding the first prostacyclin prescription (any formulation) to the 6 months subsequent, mean overall health care costs rose from $61,243 to $119,283, and PAH-related health care costs increased from $58,815 to $116,661, driven mainly by PAH-specific medications, spending on which increased from $15,053 to $73,705 (all P < 0.001). CONCLUSIONS: While overall use of prostacyclins was relatively constant from 2010 to 2015, our findings revealed a shift from parenteral to nonparenteral formulations, coupled with increased prescribing of PAH-related medications from other drug classes. Further research is needed to better understand how these changes in patterns of prostacyclin use affect levels of health care resource utilization and costs and patients' overall quality of life. DISCLOSURES: This research was funded by Actelion Pharmaceuticals US, a Janssen pharmaceutical company of Johnson & Johnson. Burger has received grant funding from Actelion, Gilead Sciences, and United Therapeutics; personal fees from Actelion and Gilead Sciences; and nonfinancial support from Actelion. Pruett, Lickert, and Drake are employees of Actelion. Pruett and Lickert own shares in Actelion. Berger and Murphy are employees of Evidera, a consultancy that received payment from Actelion to conduct this research. Pruett, Lickert, Berger, and Drake contributed to study conception and participated with Burger in study design. Lickert and Murphy performed the data analyses. Burger, Pruett, Lickert, Murphy, and Drake interpreted the data. All authors participated in manuscript drafting and/or critical revision, approved the final manuscript, and agree to be accountable for all aspects of the work.

Análisis de impacto presupuestal de ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, sildenafil y treprostinil para el tratamiento de pacientes con Hipertensión Arterial Pulmonar Grupo 1 en Colombia / Budget impact analysis of ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, sildenafil and treprostinil for the treatment of patients with hypertension Pulmonary Artery Group 1 in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) de ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, sildenafil y treprostinil para el tratamiento de pacientes con Hipertensión Arterial Pulmonar Grupo 1 en Colombia, se desarrolló en el marco del mecanismo técnico-científico para la ampliación progresiva del Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Regulación de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. La hipertensión arterial pulmonar grupo 1 (HAPG1) es una enfermedad progresiva causada por el estrechamiento o constricción de las arterias pulmonares que conectan el lado derecho del corazón con los pulmones. La HAPG1 se caracteriza por un aumento en la presión arterial pulmonar media (PAP) ≥25 mmHg en reposo y una presión capilar primaria media ≤15 mmHg (1). A medida que se desarrolla la HAPG1, el flujo de sangre a través de las arterias pulmonar

Prostacyclin as an Anticoagulant for Continuous Renal Replacement Therapy in Children.

Effective delivery of continuous renal replacement therapy (CRRT) depends on the longevity of the filter and circuit used in the CRRT machine. Safe and effective anticoagulation is crucial for maintaining the patency of these circuits. In children, heparin and citrate are the commonly used anticoagulants but they are limited by serious side effects and thus calls for meticulous monitoring. In conditions where neither of these can be used, prostacyclin can be an effective alternative. Prostacyclin is a platelet inhibitor that can be safely used as an efficient anticoagulant in CRRT. When combined with heparin, it induces a heparin-sparing effect, which can reduce the dosage and side effects of heparin. Furthermore, there is no need for performing time-consuming monitoring tests. Although prostacyclin seems to be an attractive option, there is scanty evidence about its use as an anticoagulant in CRRT in children. We review the evidence and practicalities, and propose a guideline for the use of prostacyclin as an anticoagulant in children requiring CRRT.

Cost effectiveness of prostacyclins in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is considered an orphan disease. Prostacyclins are the keystone for PAH treatment. Choosing between the three available prostacyclin therapies could be complicated because there are no comparison studies, so the final decision must be driven by factors such as efficacy, administration route, safety profile and economic aspects. OBJECTIVE: This study provides a cost-effectiveness and cost-utility comparison of initiating prostacyclin therapy with three different treatment alternatives (inhaled iloprost [ILO], intravenous epoprostenol [EPO] and subcutaneous treprostinil [TRE]) for patients with PAH. The goal of this work is to help physicians with their therapeutic decision-making. METHODS: A Markov model was built to simulate a patient cohort with class III PAH according to the classification of the New York Heart Association (NYHA). Four health states corresponding with the NYHA classes plus death were allowed for patients in the model. Changing the treatment was possible when patients worsened from functional class III to IV. The time horizon was 3 years, allowing patients to transition between health states on a 12-week cycle basis. The study perspective was that of the National Health System (NHS) [only direct medical costs were included]. Unitary costs were obtained from the Drug Catalogue and e-Salud Database in 2009 and are given in euros (€). Data on health resources and treatment pathways were informed by a four-member expert panel. Efficacy was obtained from pivotal clinical trials of ILO, EPO and TRE, the latter used in Spain as a foreign medication. Utilities for each health state were obtained from the literature. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). Costs and effects were discounted at a 3% rate. To check for the robustness of the results, sensitivity analyses were performed. RESULTS: At the end of the 3 years, in the base case of the deterministic analysis, initiating prostacyclin therapy with iloprost was the less costly strategy (€132,840), followed by treprostinil (€359,869) and epoprostenol (€429,775). Epoprostenol has shown the best efficacy results with 2.73 LYG and 1.78 QALY, followed by iloprost (2.69 LYG and 1.74 QALY) and treprostinil (2.69 LYG and 1.73 QALY). Incremental cost-effectiveness ratios (ICER) and cost-utility ratios (ICUR) of epoprostenol versus iloprost and treprostinil were much above the €30,000 per LYG or QALY threshold commonly used in Spain. Iloprost was dominant compared with treprostinil. In the probabilistic analysis, epoprostenol, when compared with iloprost, was a dominant strategy in 15% of the simulations, but it was not a cost-effective option in 83% of the cases. When compared with treprostinil, epoprostenol was dominant in 43% of the simulations. Iloprost was dominant compared with treprostinil in 45% of the cases and it was a cost-effective alternative in 39% of the simulations. CONCLUSIONS: Initiating prostacyclin treatment with iloprost in patients with PAH, functional class III of the NYHA, is the less costly alternative for the NHS in Spain, with a good efficacy profile when compared with the other alternatives.

A pulmonary hypertension gas exchange severity (PH-GXS) score to assist with the assessment and monitoring of pulmonary arterial hypertension.

Submaximal exercise gas analysis may be a useful method to assess and track pulmonary arterial hypertension (PAH) severity. The aim of the present study was to develop an algorithm, using exercise gas exchange data, to assess and monitor PAH severity. Forty patients with PAH participated in the study, completing a range of clinical tests and a novel submaximal exercise step test, which lasted 6 minutes and incorporated rest (2 minutes), exercise (3 minutes), and recovery (1 minute) ventilatory gas analysis. Using gas exchange data, including breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse, a pulmonary hypertension gas exchange severity (PH-GXS) score was developed. Patients were retested after about 6 months. There was significant separation between healthy controls and patients with moderate PAH (World Health Organization [WHO] class I/II) and those with more severe PAH (WHO class III/IV) for breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse. The PH-GXS score was significantly correlated with WHO class (r = 0.51), 6-minute walking distance (r = -0.59), right ventricular systolic pressure (r = 0.49), log N-terminal pro-B-type natriuretic peptide (r = 0.54), and pulmonary vascular resistance (r = 0.71). The PH-GXS score remained unchanged in 22 patients retested (1.50 ± 0.92 vs 1.48 ± 0.94), as did WHO class (2.3 ± 0.8 vs 2.3 ± 0.8) and 6-minute walking distance (455 ± 120 vs 456 ± 103 m). Small individual changes were observed in the PH-GXS score, with 8 patients improving and 8 deteriorating. In conclusion, the PH-GXS score differentiated between patients with PAH and was correlated with traditional clinical measures. The PH-GXS score was unchanged in our cohort after 6 months, consistent with traditional clinical metrics, but individual differences were evident. A PH-GXS score may be a useful way to track patient responses to therapy.

Pulmonary arterial hypertension and lung transplantation.

Heart-lung transplantation (HLT) and lung transplantation (LT) remain important therapies for idiopathic pulmonary arterial hypertension (IPAH), but recent advances in medical therapy can substantially delay or even obviate the need for transplantation, especially in certain PAH populations. By the early 1990s, the advent of epoprostenol, initially introduced as a bridge therapy to transplantation, in fact resulted in a survival advantage for IPAH. These benefits were comparable to those of HLT, and many patients who were thought to be destined for HLT were subsequently removed from active listing. Since 2005, however, the impact of the new lung allocation score (LAS) on IPAH has increased waiting list mortality. In the new millennium, the balance between the role of available medical therapies for PAH, the existing issues of the current LAS regarding the PAH patient, and the inherent morbidity associated with transplantation of PAH, will be critical to optimizing patient outcomes. The following discussion mainly focuses on adult IPAH, with some reference to congenital heart disease (CHD) and secondary PAH.

Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.

OBJECTIVE(S): To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications. DATA SOURCES: Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from dossiers submitted to NICE by the manufacturers of the technologies. REVIEW METHODS: The systematic clinical and economic reviews were conducted according to accepted procedures. Model-based economic evaluations of the cost-effectiveness of the technologies from the perspective of the UK NHS and personal social services were carried out. RESULTS: In total, 20 randomised controlled trials (RCTs) were included in this assessment, mostly of 12-18 weeks duration and comparing one of the technologies added to supportive treatment with supportive treatment alone. Four published economic evaluations were identified. None produced results generalisable to the NHS. There was no consensus in the industry submissions on the most appropriate model structure for the technology assessment. Improvement in 6-minute walk distance (6MWD) was seen with intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with mixed functional class (FC) (mainly III and IV, licensed indication) compared with supportive care (58 metres; 95% CI 6-110). For bosentan compared with supportive care, the pooled result for improvement in 6MWD for FCIII patients with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40 (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care. The corresponding values for inhaled iloprost (FCIII PPH patients; licensed indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed indication) and sildenafil (FCIII patients with mixed PAH; licensed indication) were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64) and [Commercial-in-confidence information has been removed] respectively. The incremental cost-effectiveness ratios (ICERs) for the technologies plus supportive care compared with supportive care alone, determined by independent economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for FCIII and 343,000 pounds/QALY for FCIV patients for epoprostenol, 101,000 pounds/QALY for iloprost, 27,000 pounds/QALY for bosentan and 25,000 pounds/QALY for sitaxentan. For the most part sildenafil plus supportive care was more effective and less costly than supportive care alone and therefore dominated supportive care. In the case of epoprostenol the ICERs were sensitive to the price of epoprostenol and for bosentan and sitaxentan the ICERs were sensitive to running the model over a shorter time horizon and with a lower cost of epoprostenol. Two RCTs directly compared the technologies against each other with no significant differences observed between the technologies. Combinations of technologies were investigated in four RCTs, with some showing conflicting results. CONCLUSION(S): All five technologies when added to supportive treatment and used at licensed dose(s) were more effective than supportive treatment alone in RCTs that included patients of mixed FC and types of PAH. Current evidence does not allow adequate comparisons between the technologies nor for the use of combinations of the technologies. Independent economic evaluation suggests that bosentan, sitaxentan and sildenafil may be cost-effective by standard thresholds and that iloprost and epoprostenol may not. If confirmed, the use of the most cost-effective treatment would result in a reduction in costs for the NHS. Long-term, double-blind RCTs of sufficient sample size that directly compare bosentan, sitaxentan and sildenafil, and evaluate outcomes including survival, quality of life, maintenance on treatment and impact on the use of resources for NHS and personal social services are needed.

The cost-effectiveness of bosentan in the United Kingdom for patients with pulmonary arterial hypertension of WHO functional class III.

OBJECTIVES: To assess whether bosentan or no active intervention, in addition to palliative care, is the more cost-effective first-line treatment option for patients with idiopathic pulmonary arterial hypertension (iPAH) or PAH associated with connective tissue disease (PAH-CTD) of WHO functional classification (FC) III in the United Kingdom. METHODS: A cost-utility model simulated the treatment of patients with PAH of FC III. Patients remained on the selected intervention until death or clinical deterioration to FC IV, which would trigger initiation of epoprostenol treatment. The initial first-line treatment choice was assumed to not affect survival, but to affect the time until clinical deterioration, with this assumption being relaxed in sensitivity analyses. The distribution of time to clinical deterioration was estimated from long-term clinical trial databases of bosentan and from published literature. Utility associated with FC was taken from published literature. Costs were sourced from published literature and from specialist PAH centers. The time horizon was that of patients' lifetimes, with costs and benefits discounted at 3.5% per annum. RESULTS: In the base case, bosentan dominated no active intervention because of the longer time to clinical deterioration and therefore the reduced time, per patient, spent in FC IV, which was associated with high costs of epoprostenol and reduced utility. In sensitivity analyses, bosentan was estimated to be more cost-effective than no active intervention, provided that any survival benefit was not greater than 2 years for patients with iPAH and 1 year for those with PAH-CTD. CONCLUSIONS: Bosentan is likely to be a more cost-effective first-line therapy for patients with PAH FC III in the UK than no active intervention.

Diagnosis and assessment of pulmonary arterial hypertension.

The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.

Epoprostenol in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease leading to right heart failure and death in a relatively young patient population. In recent years novel PAH specific therapies have become available. OBJECTIVE: To determine the place of epoprostenol in current PAH treatment strategies. METHODS: An extensive Medline search was performed to evaluate the use of epoprostenol in PAH. Data from both human and animal studies were reviewed. RESULTS/CONCLUSION: Epoprostenol is an effective and potent treatment in pulmonary arterial hypertension and has greatly improved survival, exercise capacity, PAH symptoms, pulmonary haemodynamics and disease progression. A main disadvantage is that it can only be delivered through a continuous intravenous pump infusion.

Assessment and treatment of pulmonary arterial hypertension: an Australian perspective in 2006.

Pulmonary arterial hypertension is a group of diseases which forms a small subset of those with elevated pulmonary artery pressure (pulmonary hypertension). The recent development of selective pulmonary vasodilator has lead to a substantial resurgence of interest in what have been previously regarded as rare and incurable diseases. This review aims to describe the spectrum of pulmonary vascular diseases, the evolving understanding as to pathogenesis, the evolving evidence of efficacy for drug therapies, trying to put this into a contemporary Australian context. Several key pathogenic pathways may be involved: prostacycline, Nitric Oxide-cGMP-phosphodiesterase 5 and endothelin- all of which are exploited for therapeutic benefit by newly available drug therapies. A recently modified classification system reasserts the importance of precise diagnosis. The cardinal symptom of exertional dyspnea warrants careful evaluation in an attempt to prevent (frequently occurring) substantial delay in diagnosis. Echocardiogram is the cornerstone of screening for pulmonary arterial hypertension; however, a detailed evaluation including a carefully performed right heart catheterisation with sufficient data to allow calculation of pulmonary vascular resistance is key to accurate diagnosis. These new approaches to therapy are already substantially improving quality of life and prognosis.

Cost-effectiveness of treprostinil versus epoprostenol in patients with pulmonary arterial hypertension: a Canadian analysis.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with substantial morbidity and mortality, exerting a tremendous health and economic impact on patients. In the present study, an economic evaluation of patients with PAH treated with either treprostinil or epoprostenol was performed. METHODS: A cost-minimization analysis (a cost-effectiveness subtype) was performed under the assumption that treprostinil and epoprostenol were clinically equivalent. Two cohorts of 60 patients, treated with treprostinil or epoprostenol, were evaluated over three years by using a dynamic spreadsheet model. The evaluation included both the provincial ministries of health and societal perspectives. Resource valuation data for drugs, medical supplies, consultations, and surgical and diagnostic procedures were obtained from standard lists. Costs of hospitalizations and adverse events were derived from published sources. Additional outpatient costs were considered equivalent and, therefore, were excluded from the analysis. Costs are presented in 2003 Canadian dollars discounted at 3%. Sensitivity analyses were performed testing all uncertainties in the model. RESULTS: In the base-case analysis (over three years), treatment with treprostinil resulted in an expected savings of 2,610,642 US dollars and 2,781,438 US dollars from the ministries of health and societal perspectives, respectively. On a per-patient level, treatment with treprostinil resulted in an average annual savings of 14,504 US dollars and 15,452 US dollars, respectively. The greatest savings with treprostinil came from reduced hospitalizations. Multivariate sensitivity analyses estimated cost savings in greater than 99% of scenarios. CONCLUSIONS: By initiating and continuing treprostinil treatment over a three-year period, the economic burden associated with PAH may be reduced compared with epoprostenol treatment.

Cost-minimization analysis of treprostinil vs. epoprostenol as an alternate to oral therapy non-responders for the treatment of pulmonary arterial hypertension.

INTRODUCTION: Idiopathic pulmonary arterial hypertension (IPAH) is associated with substantial morbidity and mortality. Treprostinil was compared to epoprostenol for the economic impact of treating IPAH patients who failed or were not candidates for bosentan. METHODS: The model was a cost-minimization analysis, assuming clinical equivalence was achieved by proper dosing of both drugs, in terms of survival and surrogate measures. Two theoretical cohorts of 270 patients were treated with subcutaneous treprostinil and intravenous epoprostenol, and were evaluated over 3 years using a spreadsheet model. Annual survival rates were estimated for the cohorts so that at endpoint 114 (42%) patients survived in both groups. The model utilized resource valuation data for medication and supply costs from Medicare; hospital, consultation, surgical, and diagnostic procedural fees from North Carolina hospitals; and costs to treat adverse events from published sources. Costs were obtained from standard lists and were presented as 2003 US dollars, discounted at 3%. Sensitivity analyses were performed testing all model uncertainties. RESULTS: In the base case analysis, treprostinil demonstrated savings of 22,701 US dollars and 37,433 US dollars per patient over 1- and 3-year time horizons, respectively. The greatest savings came from reduced or minimal hospitalizations attributed to the dose titration and treatment of adverse events, such as sepsis, associated with epoprostenol and its delivery system. Probabilistic sensitivity analyses resulted in average 3-year cost-savings of 41,051 US dollars (Standard Deviation = 13,902 US dollars) per patient. CONCLUSIONS: By initiating and continuing treatment with treprostinil over a 3-year period, the economic burden associated with IPAH may be reduced compared to treatment with epoprostenol. The greatest saving with treprostinil was attributed to decreased sepsis.

Inhaled iloprost in pulmonary arterial hypertension.

OBJECTIVE: To review the pharmacology, pharmacodynamics, and clinical trials evaluating inhaled iloprost in pulmonary arterial hypertension (PAH). DATA SOURCES: A MEDLINE search (1996-February 2005) was performed using the key words pulmonary hypertension, iloprost, and epoprostenol. Information regarding Food and Drug Administration approval was obtained via the Internet. STUDY SELECTION AND DATA EXTRACTION: All clinical trials using inhaled iloprost in PAH published in English were identified. Additionally, references from the identified articles were reviewed. DATA SYNTHESIS: A stable analog of prostacyclin, inhaled iloprost is thought to promote benefit in PAH through vasodilation, antiproliferative effects, and inhibition of platelet aggregation. In a placebo-controlled trial of 203 patients, inhaled iloprost significantly improved the combined endpoint of change in New York Heart Association functional class and 10% improvement in 6-minute walk distance (p = 0.007). Small, short-term clinical trials demonstrated hemodynamic benefits for inhaled iloprost alone and in combination with other pulmonary vasodilating agents. The aerosolized delivery route and low incidence of adverse events are positive attributes for inhaled iloprost, while the frequency of administration and lack of comparative data limit its role in PAH. CONCLUSIONS: Currently, inhaled iloprost offers potential benefit for patients with contraindications to bosentan, preference for non-parenteral products, ineligibility for parenteral therapy, or as adjunctive therapy with other pulmonary vasodilators. Larger, long-term clinical trials are needed to solidify the role for inhaled iloprost in the management of PAH.

Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery.

BACKGROUND: The purpose of this study was to describe our institutional experience in using inhaled prostacyclin as a selective pulmonary vasodilator in patients with pulmonary hypertension, refractory hypoxemia, and right heart dysfunction after cardiothoracic surgery. METHODS: Between February 2001 and March 2003, cardiothoracic surgical patients with pulmonary hypertension (mean pulmonary artery pressure >30 mm Hg or systolic pulmonary artery pressure >40 mm Hg), hypoxemia (PaO(2)/fraction of inspired oxygen <150 mm Hg), or right heart dysfunction (central venous pressure >16 mm Hg and cardiac index <2.2 L.min(-1).m(-2)) were prospectively administered inhaled prostacyclin at an initial concentration of 20,000 ng/mL and then weaned per protocol. Hemodynamic variables were measured before the initiation of inhaled prostacyclin, 30 to 60 minutes after initiation, and again 4 to 6 hours later. RESULTS: One hundred twenty-six patients were enrolled during the study period. At both time points, inhaled prostacyclin significantly decreased the mean pulmonary artery pressure without altering the mean arterial pressure. The average length of time on inhaled prostacyclin was 45.6 hours. There were no adverse events attributable to inhaled prostacyclin. The average cost for inhaled prostacyclin was 150 US dollars per day. Compared with nitric oxide, which costs 3000 US dollars per day, the potential cost savings over this period were 681,686 US dollars. CONCLUSIONS: Inhaled prostacyclin seems to be a safe and effective pulmonary vasodilator for cardiothoracic surgical patients with pulmonary hypertension, refractory hypoxemia, or right heart dysfunction. Overall, inhaled prostacyclin significantly decreases mean pulmonary artery pressures without altering the mean arterial pressure. Compared with nitric oxide, there is no special equipment required for administration or toxicity monitoring, and the cost savings are substantial.

Treatment of pulmonary arterial hypertension: a preliminary decision analysis.

STUDY OBJECTIVE: New therapies for pulmonary arterial hypertension (PAH) improve functional status, quality of life (QOL), and survival. Clinicians must chose between very different therapies without the availability of comparison studies. We constructed a "virtual" clinical trial to help inform these treatment choices. DESIGN: We compare key outcomes related to survival, costs, and QOL using a Markov-type decision model to estimate the expected outcomes and costs for PAH patients treated for 1 year with bosentan and treprostinil compared to patients treated with epoprostenol, as well as patients treated with bosentan compared to those treated with treprostinil. The allowed transitions in the model were between World Health Organization functional class I to IV and death. Transition probabilities were based on observed transitions for bosentan. Treatment effect was estimated using 6-min walk data for treprostinil and epoprostenol. Utilities were calculated from estimated EuroQol health states. Cost was estimated from average wholesale price and Medicare reimbursement data. The effects of changing values of input variables on the key outcomes were calculated. RESULTS: Treatment with bosentan compared to treatment with either epoprostenol or treprostinil was less costly and resulted in a greater gain in quality-adjusted life years (QALYs). Conversely, treprostinil was significantly more expensive than epoprostenol, without an appreciable gain in QALYs. These findings were not substantially affected by the reasonable adjustments of transition probabilities, utility values, or tachyphylaxis to epoprostenol. CONCLUSION: Treatment with bosentan is more cost-effective than treatment with either treprostinil or epoprostenol. In addition, a net improvement in quality-adjusted survival may be expected.