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.

Use and costs of inhaled nitric oxide and inhaled epoprostenol in adult critically ill patients: A quality improvement project.

PURPOSE: Inhaled epoprostenol and inhaled nitric oxide are pulmonary vasodilators commonly used in the management of acute respiratory distress syndrome and right ventricular failure; however, they have vastly different cost profiles. The purpose of the project was to transition from nitric oxide to epoprostenol as the inhaled pulmonary vasodilator (IPV) of choice in adult critically ill patients and evaluate the effect of the transition on associated usage and costs. METHODS: A single-center, prospective, before and after quality improvement project including adult patients receiving inhaled nitric oxide, inhaled epoprostenol, or both was conducted in 7 adult intensive care units, operating rooms, and postanesthesia care units of a tertiary care academic medical center. The total number of patients, hours of therapy, and costs for each agent were compared between stages of protocol implementation and annually. RESULTS: Seven hundred twenty-nine patients received inhaled nitric oxide, inhaled epoprostenol, or both during the study period. The monthly inhaled nitric oxide use in number of patients, hours, and cost decreased during all stages of the project (p < 0.01). The monthly inhaled epoprostenol use in number of patients, hours, and cost increased during all stages (p < 0.01). Overall, total IPV use increased during the study. However, despite this increase in usage, there was a 47% reduction in total IPV cost. CONCLUSION: Implementation of a staged protocol to introduce and expand inhaled epoprostenol use in adult critically ill patients resulted in decreased use and cost of inhaled nitric oxide. The total cost of all IPV was decreased by 47% despite increased IPV use.

Effectiveness, safety, and Economic Comparison of Two Inhaled Epoprostentol Products (Flolan and Veletri) in Cardiothoracic Surgery Patients.

BACKGROUND: No previous studies exist examining two inhaled epoprosternol formulations (Flolan compared with Veletri) in a homogenous cardiothoracic surgery patient population. OBJECTIVE: To compare the impact of inhaled Flolan and inhaled Veletri on the effectiveness, safety, or cost in cardiothoracic surgery patients. MATERIALS AND METHODS: This was a retrospective, noninferiority study comparing inhaled Flolan and inhaled Veletri in cardiothoracic surgery patients. Participants included were ≥18 years old, admitted to the cardiothoracic intensive care unit, and received inhaled Flolan or inhaled Veletri therapy for ≥1 hour. RESULTS: A total of 244 patients were included in the primary outcome analysis (122 patients per group). The primary outcome, change in the partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio 1 hour after administration of inhaled Flolan or inhaled Veletri, did not cross the lower limit of the noninferiority margin (95% CI = -14.8 to 65.4). Significant differences in secondary outcomes included duration of mechanical ventilation (4.4 vs 2.6 days; P < 0.01), number of tracheostomies (24 vs 9; P = 0.01), number of patients initiated on dialysis (25 vs 12; P = 0.02), and cost per median duration of therapy ($257 vs $183; P = 0.02) in the inhaled Flolan and inhaled Veletri groups, with the average duration of therapy being 1.6 and 1.3 days, respectively. CONCLUSIONS AND RELEVANCE: Inhaled Veletri was demonstrated to be non-inferior to inhaled Flolan when comparing change in PaO2/FiO2 ratio 1 hour post -therapy initiation,and inhaled Veletri was an acceptable alternative to inhaled Flolan in a cardiothoracic surgery patient population.

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.

Cost-utility and budget impact analysis of drug treatments in pulmonary arterial hypertension associated with congenital heart diseases in Thailand.

OBJECTIVE: This study aims to compare the lifetime costs and health outcomes of both first-line and sequential combination treatments with standard treatment for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH-CHD) patients. METHODS: A cost-utility analysis was performed using a Markov model based on a societal perspective. One-way and probabilistic sensitivity analyses were performed to investigate the effect of parameter uncertainty. RESULTS: As first-line treatments, both beraprost (incremental cost-effectiveness ratio (ICER) = 192,752 and 201,308 Thai baht (THB) per quality-adjusted life year (QALY) gained) and sildenafil (ICER = 249,770 and 226,802 THB per QALY gained) seemed cost-effective for PAH-CHD patients aged ≤30 years in functional classes II and III, respectively, while no treatment was cost-effective for the sequential combination therapy. CONCLUSIONS: Sildenafil should be included in the National Drug List of Essential Medicines as the first-line treatment for PAH-CHD, and its price per dose should be negotiated to be reduced by 43-57%.

A Comparison of Inhaled Nitric Oxide Versus Inhaled Epoprostenol for Acute Pulmonary Hypertension Following Cardiac Surgery.

BACKGROUND: Direct comparisons of inhaled nitric oxide (iNO) to inhaled epoprostenol (iEPO) in patients with acute pulmonary hypertension (PHT) following cardiac surgery are lacking. OBJECTIVE: To compare the relative efficacy, safety, and cost of iNO versus iEPO in patients with acute PHT following cardiac surgery. METHODS: This is a single-center, retrospective, observational, cohort study comparing iNO to iEPO for acute postoperative PHT following cardiac surgery. The primary outcome was reduction of mean pulmonary artery pressure (mPAP) to < 30 mm Hg, 6 hours after ICU admission from the operating room. Secondary outcomes, included ICU and hospital length of stay, duration of mechanical ventilation, bleeding complications, hypotension, in-hospital mortality, and cost. RESULTS: A total of 98 patients met inclusion criteria (iNO, n = 49; iEPO, n = 49). There was no difference in the primary outcome of reduction of mPAP to < 30 mm Hg 6 hours after ICU admission (iNO, 33 [67%] vs iEPO, 35 [71%]; P = 0.83) or in the incidence of adverse events collected (iNO, 10 [20%] vs iEPO, 11 [22%]; P = 1.00). Based on cost estimates, the median cost of iEPO per patient was $363.53 ($226-$864.60) versus $2562.50 ($1875-$8625) for iNO (P < 0.01). CONCLUSIONS: The relative efficacy of iEPO appeared to be similar to that of iNO in reducing mPAP following cardiac surgery, in this retrospective review. Significant cost savings were associated with the use of iEPO.

The role of inhaled prostacyclin in treating acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute lung injury that is characterized by noncardiogenic pulmonary edema and severe hypoxemia second to a pathogenic impairment of gas exchange. Despite significant advances in the area, mortality remains high among ARDS patients. High mortality and a limited spectrum of therapeutic options have left clinicians searching for alternatives, spiking interest in selective pulmonary vasodilators (SPVs). Despite the lack of robust evidence, SPVs are commonly employed for their therapeutic role in improving oxygenation in patients who have developed refractory hypoxemia in ARDS. While inhaled epoprostenol (iEPO) also impacts arterial oxygenation by decreasing ventilation-perfusion (V/Q) mismatching and pulmonary shunt flow, this effect is not different from inhaled nitric oxide (iNO). The most effective and safest dose for yielding a clinically significant increase in PaO2 and reduction in pulmonary artery pressure (PAP) appears to be 20-30 ng/kg/min in adults and 30 ng/kg/min in pediatric patients. iEPO appears to have a ceiling effect above these doses in which no additional benefit may be derived. iNO and iEPO have shown similar efficacy profiles; however, they differ with respect to cost and ease of therapeutic administration. The most beneficial effects of iEPO have been seen in adult patients with secondary ARDS as compared with primary ARDS, most likely due to the difference in etiology of the two disease states, and in patients suffering from baseline right ventricular heart failure. Although iEPO has demonstrated improvements in hemodynamic parameters and oxygenation in ARDS patients, due to the limited number of randomized clinical trials and the lack of studies investigating mortality, the use of iEPO cannot be recommended as standard of care in ARDS. iEPO should be reserved for those refractory to traditional therapies.

Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients.

PURPOSE: The purpose of this is to compare efficacy, safety, and cost outcomes in patients who have received either inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO) for hypoxic respiratory failure. MATERIALS AND METHODS: This is a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iNO or iEPO for improvement in oxygenation. RESULTS: We evaluated 105 mechanically ventilated patients who received iEPO (52 patients) or iNO (53 patients) between January 2009 and October 2010. Most patients received therapy for acute respiratory distress syndrome (iNO 58.5% vs iEPO 61.5%; P=.84). There was no difference in the change in the partial pressure of arterial O2/fraction of inspired O2 ratio after 1 hour of therapy (20.58±91.54 vs 33.04±36.19 [P=.36]) in the iNO and iEPO groups, respectively. No difference was observed in duration of therapy (P=.63), mechanical ventilation (P=.07), intensive care unit (P=.67), and hospital lengths of stay (P=.26) comparing the iNO and iEPO groups. No adverse events were attributed to either therapy. Inhaled nitric oxide was 4.5 to 17 times more expensive than iEPO depending on contract pricing. CONCLUSIONS: We found no difference in efficacy and safety outcomes when comparing iNO and iEPO in hypoxic, critically ill patients. Inhaled epoprostenol is associated with less drug expenditure than iNO.

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.

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.

Role of prostacyclin (epoprostenol) as anticoagulant in continuous renal replacement therapies: efficacy, security and cost analysis.

BACKGROUND: Heparin remains the drug most commonly used for anticoagulation in continuous renal replacement therapies (CRRTs). However, in patients with hypercoagulability, heparin is insufficient or, in cases with an increased risk of bleeding or thrombocytopenia, it may be contraindicated. Epoprostenol, a potent vasodilator, antithrombotic and antiplatelet agent, could be an alternative. PATIENTS AND METHODS: We studied the records of patients treated under continuous venovenous hemodiafiltration in an academic tertiary hospital of 900 beds, between January 2000 and June 2003. Epoprostenol was prescribed to patients with (i) filter hypercoagulability, defined as consumption of 2 or more filters in the last 24 hours; (ii) low platelet count; or (iii) recent severe hemorrhage. RESULTS: Thirty-eight out of 248 (15%) patients who were under CRRT received epoprostenol for more than 72 hours. Epoprostenol was indicated due to filter hypercoagulability in 48%, thrombocytopenia in 68% (7 patients both) and hemorrhage in 3% of cases. The overall time for epoprostenol therapy was 9,749 hours. The mean filter duration previous to epoprostenol was 23 +/- 12 hours and after administering this drug 38.2 +/- 11.9 hours (p = 0.0001). In 6 patients, heparin and epoprostenol were simultaneously administered. The adverse effects were hemorrhage, which presented in 7 patients (18%) and a fall in blood pressure in another 7 (18%), which recovered in the next 24 hour after starting treatment. Cost analysis demonstrates some advantage with epoprostenol in patients with increased tendency to clotting. CONCLUSIONS: Epoprostenol may be safely used to prevent clotting of the extracorporeal circuits, either alone in patients with thrombocytopenia and/or increased risk of bleeding, or in combination with heparin in states of hypercoagulability.

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.

Prostacyclin versus citrate in continuous haemodiafiltration: an observational study in patients with high risk of bleeding.

BACKGROUND: The efficacy and safety of prostacyclin (PGI2) and citrate (ACD) anticoagulation were observed and compared during continuous haemodiafiltration. METHODS: Mechanically ventilated patients received either the PGI2 analogue epoprostenol (group A, n = 17) in escalating doses of 4.5-10.0 ng.kg(-1).min(-1) in combination with heparin (6 IU.kg(-1).h(-1)) or 2.2% ACD (group B, n = 15). Blood flow was set to match the circuit-filling volume per unit time equal to the intravascular half-life of PGI2. RESULTS: Median filter lifetimes were 26 h (interquartile range 16-37) in group A (39 filters) and 36.5 h (interquartile range 23-50) in group B (56 filters; p < 0.01). In group A, 4 patients (23.5%, p < 0.05) had the dose reduced due to hypotension. The final mean dose of PGI2 was 8.7 +/- 2.4 ng.kg(-1).min(-1). Four patients in group A (23.5%, p < 0.05) were switched to ACD due to a decrease in platelet count. No bleeding episodes, decrease in platelet count or adverse haemodynamic effects were encountered in group B. The cost of epoprostenol plus low dose heparin (EUR 204.73 +/- 53.04) was significantly higher than the cost of ACD-based anticoagulation (EUR 93.92 +/- 45.2, p < 0.05). CONCLUSION: ACD offers longer filter survival, has no impact on platelet count and is less expensive. Increasing the dose of PGI2 up to the average of 8.7 ng.kg(-1).min(-1) did not increase the haemodynamic side effects.

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.