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.

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 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.

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.

Cost implications of using inhaled nitric oxide compared with epoprostenol for pulmonary hypertension.

OBJECTIVE: To compare the cost of using intravenous epoprostenol with that of inhaled nitric oxide (NO) for treating episodes of pulmonary hypertension in children with congenital heart disease. DESIGN: An analysis of the cost of epoprostenol and NO use over the previous 18 months was performed. Three 6-month periods were identified, two in which epoprostenol was used and the third in which inhaled NO was introduced for the treatment of pulmonary hypertension. SETTING: A 10-bed pediatric cardiac intensive care unit, Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England. SUBJECTS: Children with congenital heart disease and persistently elevated pulmonary artery pressure following cardiac surgery. MAIN OUTCOME MEASURES: The total duration of use of epoprostenol and inhaled NO was documented. The costs per hour for epoprostenol and inhaled NO were calculated and the annual cost of each agent was estimated. RESULTS: In the two 6-month periods prior to the introduction of inhaled NO, epoprostenol was used on 14 occasions (5 in the first period, 3 in the second). In the last 6-month period, nine children required pulmonary vasodilator therapy on 14 occasions. All nine children were treated successfully with inhaled NO; none were given or needed epoprostenol, as NO always was effective in providing pulmonary vasodilatation. For resistant pulmonary hypertension, increasing the concentration of NO would have been the next therapeutic option. The cost for the two 6-month periods using epoprostenol was $19,483.48 for the drug and $283.25 for equipment costs (total cost $19,766.73). There was no expenditure on epoprostenol in the final 6-month period. The cost of NO was $465. However, the total expenditure, including the delivery and monitoring system, was $4,722.85. CONCLUSIONS: Using inhaled NO in our pediatric cardiac intensive care unit abolished the use of epoprostenol during the reported monitoring period. The cost savings were significant, amounting to 12% of the annual drug budget for the unit. The cost of setting up the inhaled NO delivery system is recouped rapidly. The ease of delivery and measurement of inhaled NO also may have contributed to its increased clinical use.