Treprostinil-Based Therapy in the Treatment of Moderate-to-Severe Pulmonary Arterial Hypertension* Long-term Efficacy and Combination With Bosentan

Size: px
Start display at page:

Download "Treprostinil-Based Therapy in the Treatment of Moderate-to-Severe Pulmonary Arterial Hypertension* Long-term Efficacy and Combination With Bosentan"

Transcription

1 CHEST Treprostinil-Based Therapy in the Treatment of Moderate-to-Severe Pulmonary Arterial Hypertension* Long-term Efficacy and Combination With Bosentan Raymond L. Benza, MD; Barry K. Rayburn, MD; Jose A. Tallaj, MD; Salpy V. Pamboukian, MD; and Robert C. Bourge, MD Original Research PULMONARY ARTERIAL HYPERTENSION Background: Treprostinil, a long-acting prostacyclin analog, diminished the symptoms of pulmonary arterial hypertension (PAH) in controlled 12-week clinical efficacy studies. This retrospective, single-center, open-label study was designed to assess the efficacy of long-term, subcutaneously administered, treprostinil-based therapy alone or in combination with bosentan for the treatment of moderate-to-severe PAH. Methods: Thirty-eight patients with pulmonary hypertension treated with subcutaneous treprostinil were followed up for a mean ( SD) duration of days (range, 165 to 1,847 days). Oral bosentan was added to the treprostinil regimen if patients remained in New York Heart Association (NYHA) functional class III or II with intolerable prostacyclin side effects that limited therapy. Hemodynamic studies, Borg dyspnea score evaluations, 6-min walk (6MW) tests, and NYHA functional class determinations were performed at approximately 6-month intervals. Results: Mean pulmonary artery pressure decreased from 59.7 to 50.5 mm Hg (p < 0.001). Significant and sustained improvement in 6MW distance (p 0.022) and Borg dyspnea score (p 0.023) were observed. At the final observation, the mean dose of treprostinil was 37.8 ng/kg/min (range, 7.5 to 115 ng/kg/min). At baseline, 5% of patients were in NYHA functional class 2 or lower vs 58% at the last follow-up. Bosentan was added to the regimens of 19 patients. In those patients, significant additional improvement occurred in the pulmonary arterial pressure (p < 0.001), 6MW distance (p 0.001), and Borg dyspnea scale (p 0.020) compared to baseline. Conclusions: Long-term treatment with subcutaneous treprostinil-based therapy improved functional parameters and hemodynamics in patients with moderate-to-severe PAH. In patients requiring combination therapy, the addition of oral bosentan to treprostinil-based therapy was safe, welltolerated, and associated with further clinical improvements. (CHEST 2008; 134: ) Key words: bosentan; combination drug therapy; prostacyclin; pulmonary hypertension; treprostinil sodium Abbreviations: ALT alanine aminotransferase; AST aspartate aminotransferase; CCB calcium channel blocker; ET endothelin; NYHA New York Heart Association; PAH pulmonary arterial hypertension; PVR pulmonary vascular resistance; SMC smooth muscle cell; 6MW 6-min walk Pulmonary arterial hypertension (PAH), identified by an elevation in pulmonary arterial pressure and pulmonary vascular resistance (PVR), is a severe hemodynamic abnormality that is common to a variety of diseases and syndromes. 1 PAH is a life-threatening condition that is characterized by vasoconstriction and vascular remodeling within small-caliber pulmonary arteries. 2 The resulting progressive increases in mean pulmonary arterial pressure and PVR frequently cause an increase in right ventricular afterload, impairing right ventricular function that culminates in fatal right-heart failure, and ultimately leading to inactivity and death. 1 The development of pulmonary arterial vasculopathy is a consequence of endothelial injury from external stimuli, such as hypoxia or anorexigens, or a CHEST / 134 / 1/ JULY,

2 systemic process, such as a connective tissue disease that initiates a neurohormonal imbalance in susceptible individuals. 2,3 The overproduction of mediators such as endothelin (ET)-1, angiotensin II, thromboxane A2, and serotonin and the concomitant decrease in the production of nitric oxide and prostacyclin lead to vasoconstriction, smooth muscle cell (SMC) proliferation, and the promotion of profibrotic and/or prothrombotic effects The goals of PAH treatment are to improve survival, ameliorate symptoms of PAH, and improve quality of life. The development of novel therapeutic agents has improved the outcome for patients with PAH 12 ; however, despite treatment, patients may remain symptomatic and disease progression may still occur. Combination therapy with agents targeting different mechanisms of action is currently under evaluation to counteract the multiple pathophysiologic processes present in PAH. 13 Prostacyclin analogues activate the prostacyclin receptor pathway, leading to SMC relaxation and the inhibition of SMC proliferation and platelet activity via the following distinct second messenger: cyclic adenosine monophosphate. 14,15 Treprostinil sodium, a stable prostacyclin analog that is administered as a continuous infusion, is approved for the treatment of PAH in patients with New York Heart Association (NYHA) functional class II-IV symptoms to diminish symptoms associated with exercise. Bosentan is an approved orally active competitive antagonist of the endothelial ETA/ETB receptors for the treatment of PAH. ET receptor antagonists block the effects of the ET-1 signaling pathway, which produces vasoconstriction and SMC proliferation, and induces fibrosis. 10,16 The addition of bosentan to treprostinil-based therapy may provide meaningful and clinically relevant improvement to patients with persistent symptoms and/or persistent prostacyclin side effects that limit therapy. *From the Department of Medicine, Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL. Drs. Benza and Rayburn have received prior research support from United Therapeutics and Actelion; they have served on the Actelion speaker s bureau. Dr. Bourge has served as a paid consultant to United Therapeutics and Actelion. Drs. Tallaj and Pamboukian have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Manuscript received August 21, 2007; revision accepted February 29, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Raymond L. Benza, MD, Department of Medicine, Division of Cardiovascular Diseases, University of Alabama at Birmingham, 321 THT, 1900 University Blvd, Birmingham, AL 35294; rbenza@uab.edu DOI: /chest The objective of this retrospective, open-label study was to assess long-term efficacy in patients with moderate-to-severe PH who are receiving subcutaneous treprostinil as primary therapy. Additionally, the safety and benefit of the addition of bosentan to treprostinil-based therapy was evaluated in a cohort of subjects. Patients and Procedures Methods and Materials All patients described in this study were followed up in the Pulmonary Vascular Disease Clinic at the University of Alabama at Birmingham, had a diagnosis of pulmonary hypertension, and were classified utilizing the World Health Organization criteria. 17 The University of Alabama at Birmingham Institutional Review Board approved the anonymous collection and analysis of the clinically obtained data. All data reported in this study were collected per routine clinical practice. Baseline information, including demographics, duration of diagnosis, current medical therapy, and clinical characteristics, was available for all patients. Hemodynamic studies, 6-min walk (6MW) tests, Borg score assessments, and NYHA functional classifications were performed by routine clinical practice, before treatment and at approximately 6-month intervals. When available, these data were collected from patient medical records. Hemodynamic and echocardiographic data were available on those patients requiring the addition of bosentan and had been performed within 90 days prior to the initiation of this therapy. Cardiac output measurements were made using the estimated Fick method for each patient. The potential side effects of therapy, peripheral oxygen saturation, weight, vital signs, and laboratory data (including electrolyte levels, liver function test results, and brain natriuretic peptide levels) were collected by routine clinical practice. Treatment and Dosing All patients received subcutaneous treprostinil infusions. Treprostinil infusions were titrated per the investigator s judgment to achieve the maximum tolerated dose in terms of adverse events while maximizing the improvement in clinical signs and symptoms and exercise capacity. The addition of bosentan to therapy was considered if patients were persistently in NYHA functional class III or worse, or were in NYHA class II and were experiencing major side effects from prostacyclin-based therapy, necessitating a dose reduction. Bosentan, when required, was started at a dose of 62.5 mg bid and was titrated to 125 mg bid, according to standard clinical practice. In patients with an open shunt or a systolic BP of 90 mm Hg, bosentan therapy was initiated at a dose of mg bid. Prostacyclin doses were held constant for the initial 3 months of bosentan therapy, except in the case of clinical deterioration requiring a dose increase. Background PAH therapies (eg, anticoagulants, other oral vasodilators, cardiac glycosides, diuretic agents, and supplemental oxygen) were administered at the discretion of the treating physicians and were held constant during the first 90 days of bosentan therapy. Outcome Measures The end point of the study was to evaluate the long-term efficacy of subcutaneous treprostinil and the safety and efficacy of 140 Original Research

3 adding bosentan to treprostinil-based therapy for the treatment of moderate-to-severe PAH. The efficacy end points were the 6MW test results and hemodynamic parameters. The safety profile was assessed on the basis of recorded adverse events and clinical laboratory variables. Not all subjects underwent every laboratory test. The data were evaluated before the initiation of treprostinil therapy and for up to 24 months of follow-up. For patients who had bosentan added to their treprostinil therapy, data were evaluated before the addition of bosentan and during combination therapy. Statistical Analysis All available data points were analyzed. For each efficacy parameter, the latest available data point was carried forward for analysis. Follow-up values for efficacy parameters were compared to baseline values using the Wilcoxon signed rank test. Baseline and final laboratory values were compared using a T-statistic test. A two-sided p value of 0.05 was considered to be significant. Results Patients meeting the entry criteria were treated from December 1998 to July Of the 38 patients enrolled in the study, 16 had idiopathic PAH. Other etiologies of PAH included eight patients with connective tissue disease, six patients with congenital heart disease, and three patients with portopulmonary hypertension. Two patients had pulmonary hypertension due to thromboembolic disease. At baseline, 23 patients were classified as being in NYHA functional class III, 6 patients were in NYHA functional class IV, and 1 patient was in NYHA functional class II. Baseline demographic characteristics and hemodynamics are depicted in Table 1. The mean duration of treprostinil exposure was 984 days (range, 165 to 1,847 days). At final observation, the mean treprostinil dose was ng/kg/min. Exercise Capacity, Borg Dyspnea Score, and NYHA Functional Class Patients receiving long-term treprostinil-based therapy experienced an increase in their 6MW distance from 306 m at baseline to 341 m at the last follow-up (p 0.022). The Borg dyspnea score also significantly improved, from 3.8 to 2.9, respectively (p 0.023). NYHA functional class was significantly improved compared to baseline (p ) [Fig 1]. Four patients had a change in NYHA functional class from class IV to class II. At final observation, no patients were classified as being in NYHA functional class IV. No patient deaths occurred during the course of the observation period. Hemodynamics Patients receiving long-term treprostinil-based therapy demonstrated favorable effects on hemodynamics Table 1 Baseline Patient Characteristics* Characterstics and exercise tolerance at the last follow-up (Table 2). The mean time between baseline and the last right heart catheterization was 32 months. The mean pulmonary artery pressure decreased from to mm Hg, respectively (p 0.001). The mean cardiac output increased from 4.92 to 5.34 L/min, respectively (p 0.028). In addition, there was an overall trend toward improvement in mean PVR, with a decrease from to dyne s cm 5, respectively (p 0.113). Treprostinil and Bosentan Combination Therapy Bosentan was added to the treatment regimens of 19 patients who were receiving subcutaneous treprostinil monotherapy and had remained in NYHA functional class III after a year of therapy (n 12) or who had experienced intolerable side effects (n 7) while receiving treprostinil monotherapy. Patients Figure 1. Change in NYHA functional class. Values Gender Male 11 Female 27 Race White 30 African origin 6 Other 2 Age, yr 48.9 (17 76) Etiology WHO group I 36 IPAH 16 APAH 20 WHO group IV 2 NYHA functional class I 0 II 2 III 29 IV 7 *Values are given as No., unless otherwise indicated. WHO World Health Organization. Values are given as the mean (range). CHEST / 134 / 1/ JULY,

4 Table 2 Change in Hemodynamics and Exercise Capacity for Patients Receiving Long-term Treprostinil-Based Therapy* Variables Patients, No. Therapy-Naive Baseline Last Follow-up p Value Hemodynamics PAP, mm Hg RAP, mm Hg PVR, dyne s cm CO, L/min Exercise capacity 6MW test distance, m Borg dyspnea score *Values are given as the mean SD, unless otherwise indicated. PAP pulmonary artery pressure; CO cardiac output; RAP right atrial pressure. had received therapy with treprostinil for a mean duration of days at a mean dose of ng/kg/min at the time of bosentan therapy initiation. Table 3 depicts both the baseline, therapynaive characteristics of patients who continued to receive treprostinil monotherapy or had bosentan added to their treprostinil-based therapy, as well as the duration and timing of their therapy and the end of the observation of treprostinil doses. The mean follow-up time while patients received combination therapy was days. In these patients, the last observation while patients received combination therapy was compared to their baseline pre-treprostinil therapy and pre-bosentan therapy values. In patients who required combination therapy, significant improvement occurred in the mean pulmonary arterial pressure (p 0.001), 6MW distance (p 0.001), and Borg dyspnea scale score (p 0.020) compared to baseline. Serial improvements were noted in right atrial pressure, cardiac index, and PVR (Table 4). At the last observation while the patients received combined therapy, 12 patients were in NYHA functional class II, five patients were in NYHA functional class III, and one patient was classified as being in NYHA functional class I. Treprostinil doses were essentially unchanged in patients who received combination therapy; the mean treprostinil dose at the time of the final observation was ng/kg/min. Safety and Tolerability Subcutaneous treprostinil-based therapy in combination with bosentan was safe. Small, but statistically significant, changes from baseline to final laboratory measurements were observed for aspartate aminotransferase (AST) [ U/L], alanine aminotransferase (ALT) [ U/L], and hemoglobin ( g/dl; p 0.05 for all). A mean decrease of 69.8 mg/ml in brain natriuretic peptide levels was observed in patients (n 13). The Table 3 Characteristics by Bosentan Status* Characteristics Remodulin Monotherapy (n 19) Bosentan Added to Remodulin Therapy (n 19) p Value Therapy-naive baseline 6MWD Therapy-naive baseline hemodynamics PAP, mm Hg RAP, mm Hg PVR, dyne s cm CO, L/min Therapy-naive baseline NYHA functional class I II III IV Time of last follow-up, d (165 1,491) 1,255.6 (482 1,847) Time to initiation of bosentan therapy (398 1,266) Remodulin dose at last follow-up, ng/kg/min 31.2 (7.5 85) 44.4 (15 115) *Values are given as the mean SD or mean (range), unless otherwise indicated. See Table 2 for abbreviations not used in the text. Data available for 14 of 19 patients. Data available for 17 of 19 patients. Data available for 15 of 19 patients. 142 Original Research

5 Table 4 Hemodynamics and Exercise Capacity With Remodulin Plus Bosentan Combination Therapy* p Value Variables Patients, No. Therapy-Naive Baseline Pre-Bosentan Therapy Last Follow-up While Receiving Combination Therapy Compared to Baseline Values Compared to Pre-Bosentan Therapy Values Hemodynamics PAP, mm Hg RAP, mm Hg PVR, dyne s cm CO, L/min Exercise capacity 6MWT, m Borg dyspnea score *Values are given as the mean SD, unless otherwise indicated. See Table 2 for abbreviations not used in the text. mean decline in hemoglobin observed in patients receiving bosentan was consistent with the known effect of bosentan on clinical laboratory parameters. A small improvement in AST and ALT levels was observed in patients receiving the combination therapy. Discussion In this retrospective, single-center study, longterm treatment with a subcutaneous treprostinilbased therapy was observed to provide a sustained improvement in functional parameters and hemodynamics in patients with moderate or severe pulmonary hypertension. Barst et al 18 reported survival rates for subcutaneous treprostinil monotherapy of 88% at year 1 and 70% at year 4, which are comparable to the survival benefit of epoprostenol relative to predicted survival rates of 69 to 38% from published registry survival curves. 15 The overall survival rates for patients receiving subcutaneous treprostinil therapy in a European retrospective study of 122 patients with PAH or chronic thromboembolic pulmonary hypertension were 88.6% and 70.6%, respectively, at 1 year and 3 years, and the event-free survival rates were 83.2% and 69%, respectively. Additionally, and notably, this is the first report on long-term sustained clinical improvement (18 4 months) with the combined use of treprostinil and bosentan. 19 We observed that the addition of bosentan to continuous subcutaneous treprostinil therapy may be accomplished without serious adverse events, and that it was associated with further improvements in exercise capacity, hemodynamics, and functional class. Perturbation in the balance of several endogenous mediators involved in maintaining endothelial function have been identified in the pathogenesis of PAH; among these are a deficiency in prostacyclin and nitric oxide, and an excess of ET-1, thromboxane, and serotonin. 5 11,14 The addition of bosentan to treprostinil-based therapy to simultaneously restore endothelial levels of prostacyclin, rebalance vasodilatory/vasconstrictive actions, and inhibit the proliferative effects of ET is one strategic approach to treating PAH by combining agents with distinct and complementary mechanisms of action. 13 Previous studies have reported on the shortterm benefit and safety of the combination of prostacyclin or prostacyclin analogues with ET receptor antagonism. A trend toward greater improvement in hemodynamics, exercise capacity, and functional class at week 16 was observed with the simultaneous initiation of bosentan and epoprostenol combination therapy in PAH patients in the Bosentan Randomized Trial of Endothelin Antagonist Therapy for PAH (or BREATHE-2) trial who were in NYHA functional class III-IV. 20 Hoeper et al 21 demonstrated an improvement in 6MW distance along with an increase in maximal oxygen consumption and a rise in anaerobic threshold with the addition of bosentan to nonparental prostanoid therapy. Bosentan therapy with or without concomitant prostacyclin therapy was well-tolerated and improved hemodynamics and functional class in a retrospective study of 86 children with PAH. 22 In contrast to the studies cited above, bosentan was added to treprostinil therapy in patients with suboptimally managed disease and offers an explanation for the more pronounced benefit seen with the addition of bosentan in this study compared to previous reports. Patients who had bosentan added to their treprostinil-based therapy demonstrated additional improvement in right ventricular function, as evidenced by the improvements in right atrial pressure and cardiac output. Interestingly, a small improvement in AST and ALT levels was observed in CHEST / 134 / 1/ JULY,

6 patients receiving combination therapy with bosentan and may be related to the improvement of right heart function and liver blood flow, or may also be an artifact of the small sample size. Following the addition of bosentan, the doses of treprostinil remained essentially unchanged; therefore, the outcome of decreasing the treprostinil dosage when initiating bosentan combination therapy in these patients is unknown. No patients had treprostinil therapy replaced by bosentan therapy, rather than having bosentan added to it. Whether the same degree of clinical benefit would have been observed by switching to bosentan therapy alone cannot be distinguished in the patients who received combination therapy. However, some reports published on the transition of patients from IV prostacyclin therapy to oral bosentan therapy have suggested a dependency on prostacyclin therapy, especially in patients with more advanced disease, as only a minority of patients (ie, those whose conditions were stabilized with low prostacyclin doses and with milder elevations in PAP) were successfully weaned off prostacyclin therapy. Additional clinical data are necessary to evaluate the overall safety and efficacy of reducing the prostacyclin dose in combination therapy, or discontinuing prostacyclin therapy following the addition of bosentan therapy. The clinical benefit of the addition of prostacyclin to existing bosentan therapy is also under evaluation and is a question of much clinical import, as many patients are initiated on oral bosentan therapy before treatment with other agents is initiated. The inhaled iloprost studies 27,28 have reported conflicting results regarding the benefit of the addition of prostacyclin to existing bosentan therapy. Clinical improvement has been reported 29 with the addition of inhaled treprostinil therapy for 12 PAH patients who remained symptomatic despite receiving oral bosentan therapy. Small patient numbers, the short duration of treatment, and a population with more severe disease limit the conclusions from these trials. Combination treatment with therapies targeting different mechanisms of action has great promise in addressing the multiple pathophysiologic processes present in PAH. These combinations may produce additive, even synergistic, effects or may enhance and prolong the effects of other therapeutic agents. 13 However, the optimal method to be used for combining and using therapies remains to be elucidated. Unrecognized molecular heterogeneity may underlie the variability in response to specific therapies. Based on their molecular profile, patients may respond with differing outcomes to various combinations and sequences of therapies. An example already familiar in the treatment of PAH is the use of calcium channel blockers (CCBs). For the small subset of patients who respond to CCB therapy the clinical benefit is clear; however, for the remaining majority, the use of CCBs is associated with a detrimental therapeutic effect. The main limitation of the current study is the single-center, retrospective nature of the design. The observed improvement in 6MW distance of 35 m over an average follow-up period 2 years points to a sustained functional benefit with subcutaneous treprostinil-based therapy. However, the efficacy of subcutaneous treprostinil therapy in this study may have been limited by underdosing; at the final observation, the mean treprostinil dose was 37.8 ng/kg/min. In comparison, an open-label trial 30 evaluating IV administered treprostinil demonstrated an improvement in 6MW distance of 125 m in previously untreated PAH patients at 1 year. The average dose at the end of the 1-year open-label trial was 98 ng/kg/min. Small patient numbers and the lack of placebo control prevent definitive conclusions on safety and efficacy from being drawn; however, the outcomes from this retrospective study suggest that combination therapy with the addition of the ET receptor antagonist bosentan to the prostacyclin analogue treprostinil is safe, and may be associated with improvements in functional class, exercise capacity, and hemodynamics. The expectation of combination therapy is to provide a meaningful and clinically relevant improvement and increase in quality of life to patients with persistent symptoms and/or persistent significant pulmonary hypertension despite therapy with a single drug. References 1 Rubin LJ. Primary pulmonary hypertension. N Engl J Med 1997; 336: Pietra G, Capron F, Stewart S, et al. Pathologic assessment of vasculopathies in pulmonary hypertension. J Am Coll Cardiol 2004; 12:S25 S32 3 Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43:13S 24S 4 Das S, Kumar KN. Nitric oxide: its identity and role in blood pressure control. Life Sci 1995; 57: Cooper CJ, Landzberg MJ, Anderson TJ, et al. Role of nitric oxide in the local regulation of pulmonary vascular resistance in humans. Circulation 1996; 93: Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992; 327: Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995; 333: Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: Herve P, Launay JM, Scrobohaci ML, et al. Increased plasma 144 Original Research

7 serotonin in primary hypertension. Am J Med 1995; 99: Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999; 159: Chen YF, Oparil S. Endothelial dysfunction in the pulmonary vascular bed. Am J Med Sci 2000; 320: Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004; 351: Benza R, Keogh A, Park M, et al. Management of pulmonary arterial hypertension with a focus on combination therapies. J Heart Lung Transplant 2007; 26: Cooper CJ, Landzberg MJ, Anderson TJ, et al. Role of nitric oxide in the local regulation of pulmonary vascular resistance in humans. Circulation 1996; 93: McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002; 106: Davie N, Haleen S, Upton P, et al. ETA and ETB receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med 2002; 165: Simonneau G, Galiè N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43(suppl):5S 12S 18 Barst R, Galie N, Naeije R, et al. Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J 2006; 28: Lang I, Gomez-Sanchez M, Kneussl M, et al. Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension. Chest 2006; 129: Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004; 24: Hoeper M, Taha N, Bekjarova A, et al. Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Eur Respir J 2003; 22: Rosenzweig EB, Ivy DD, Widlitz A, et al. Effects of longterm bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46: Kim N, Channick R, Rubin L. Successful withdrawal of long-term epoprostenol therapy for pulmonary arterial hypertension. Chest 2003; 124: Suleman N, Frost A. Transition from epoprostenol and treprostinil to the oral endothelin receptor antagonist bosentan in patients with pulmonary hypertension. Chest 2004; 126: Ivy D, Doran A, Claussen L, et al. Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan. Am J Cardiol 2004; 93: Steiner MK, Preston I, Klinger J, et al. Conversion to bosentan from prostacyclin therapy in pulmonary arterial hypertension: a pilot study. Chest 2006; 130: McLaughlin V, Ouditz R, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med 2006; 174: Hoeper M, Leuchte H, Halank M, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2006; 28: Channick R, Olschewski H, Seeger W, et al. Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J Am Coll Cardiol 2006; 48: McLaughlin V, Tapson V, Gomberg-Maitland M, et al. One-year experience with intravenous treprostinil for pulmonary arterial hypertension patients: a prospective, multicenter, open-label uncontrolled trial. Am J Respir Crit Care Med 2008 (in press) CHEST / 134 / 1/ JULY,

Bosentan for treatment of pulmonary arterial hypertension (I)

Bosentan for treatment of pulmonary arterial hypertension (I) KEY PAPER EVALUATION Bosentan for treatment of pulmonary arterial hypertension (I) Sabina A Antoniu University of Medicine and Pharmacy, Clinic of Pulmonary Disease, 62 Costache Negri St, Bl.C2, Sc.A,

More information

Pulmonary Hypertension. Murali Chakinala, M.D. Washington University School of Medicine

Pulmonary Hypertension. Murali Chakinala, M.D. Washington University School of Medicine Pulmonary Hypertension Murali Chakinala, M.D. Washington University School of Medicine Pulmonary Circulation Alveolar Capillary relationship Pulmonary Circulation High flow, low resistance PVR ~1/15 of

More information

Pharmacy Management Drug Policy

Pharmacy Management Drug Policy SUBJECT: Pulmonary Arterial Hypertension (PAH) POLICY NUMBER: Pharmacy-42 Clinical criteria used to make utilization review decisions are based on credible scientific evidence published in peer reviewed

More information

Disclosures. Inhaled Therapy in Pediatric Pulmonary Hypertension. Inhaled Prostacyclin: Rationale. Outline

Disclosures. Inhaled Therapy in Pediatric Pulmonary Hypertension. Inhaled Prostacyclin: Rationale. Outline Disclosures Inhaled Therapy in Pediatric Pulmonary Hypertension The University of Colorado receives fees for Dr Ivy to be a consultant for Actelion, Gilead, Lilly, Pfizer, and United Therapeutics Dunbar

More information

Pulmonary Hypertension Drugs

Pulmonary Hypertension Drugs Pulmonary Hypertension Drugs Policy Number: Original Effective Date: MM.04.028 10/01/2009 Line(s) of Business: Current Effective Date: HMO; PPO 05/25/2012 Section: Prescription Drugs Place(s) of Service:

More information

ACCP PAH Medical Therapy Guidelines: 2007 Update. David Badesch, MD University of Colorado School of Medicine Denver, CO

ACCP PAH Medical Therapy Guidelines: 2007 Update. David Badesch, MD University of Colorado School of Medicine Denver, CO ACCP PAH Medical Therapy Guidelines: 2007 Update David Badesch, MD University of Colorado School of Medicine Denver, CO Disclosure of Commercial Interest Dr. Badesch has received grant/research support

More information

Raymond L. Benza, MD, a Mardi Gomberg-Maitland, MD, MSc, b Robert Naeije, MD, PhD, c Carl P. Arneson, MStat, d and Irene M.

Raymond L. Benza, MD, a Mardi Gomberg-Maitland, MD, MSc, b Robert Naeije, MD, PhD, c Carl P. Arneson, MStat, d and Irene M. http://www.jhltonline.org Prognostic factors associated with increased survival in patients with pulmonary arterial hypertension treated with subcutaneous treprostinil in randomized, placebo-controlled

More information

Pulmonary Hypertension Drugs

Pulmonary Hypertension Drugs Pulmonary Hypertension Drugs Policy Number: Original Effective Date: MM.04.028 10/01/2009 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST Integration 05/22/2015 Section: Prescription Drugs

More information

Recent Treatment of Pulmonary Artery Hypertension. Cardiology Division Yonsei University College of Medicine

Recent Treatment of Pulmonary Artery Hypertension. Cardiology Division Yonsei University College of Medicine Recent Treatment of Pulmonary Artery Hypertension Cardiology Division Yonsei University College of Medicine Definition Raised Pulmonary arterial pressure (PAP) WHO criteria : spap>40 mmhg NIH Criteria

More information

Untreated idiopathic pulmonary arterial hypertension

Untreated idiopathic pulmonary arterial hypertension Congenital Heart Disease Outcomes in Children With Idiopathic Pulmonary Arterial Hypertension Delphine Yung, MD; Allison C. Widlitz, MS, PA; Erika Berman Rosenzweig, MD; Diane Kerstein, MD; Greg Maislin,

More information

Pulmonary Hypertension: When to Initiate Advanced Therapy. Jonathan D. Rich, MD Associate Professor of Medicine Northwestern University

Pulmonary Hypertension: When to Initiate Advanced Therapy. Jonathan D. Rich, MD Associate Professor of Medicine Northwestern University Pulmonary Hypertension: When to Initiate Advanced Therapy Jonathan D. Rich, MD Associate Professor of Medicine Northwestern University Disclosures Medtronic, Abbott: Consultant Hemodynamic Definition of

More information

Addition of Prostanoids in Pulmonary Hypertension Deteriorating on Oral Therapy

Addition of Prostanoids in Pulmonary Hypertension Deteriorating on Oral Therapy Addition of Prostanoids in Pulmonary Hypertension Deteriorating on Oral Therapy Wouter Jacobs, MD, a Anco Boonstra, MD, PhD, a J. Tim Marcus, PhD, b Pieter E. Postmus, MD, PhD, a and Anton Vonk-Noordegraaf,

More information

Pharmacy Management Drug Policy

Pharmacy Management Drug Policy SUBJECT: POLICY NUMBER: PHARMACY-42 EFFECTIVE DATE: 6/2005 LAST REVIEW DATE: 4/19/2018 If the member s subscriber contract excludes coverage for a specific service or prescription drug, it is not covered

More information

Pulmonary Hypertension in 2012

Pulmonary Hypertension in 2012 Pulmonary Hypertension in 2012 Evan Brittain, MD December 7, 2012 Kingston, Jamaica VanderbiltHeart.com Disclosures None VanderbiltHeart.com Outline Definition and Classification of PH Hemodynamics of

More information

Advances in Pharmacotherapy of PAH

Advances in Pharmacotherapy of PAH 24 th Annual Advances in Heart Disease Advances in Pharmacotherapy of PAH Gabriel Gregoratos, MD 12/14/2007 UCSF Cardiology 1 Faculty Disclosure Statement for Gabriel Gregoratos, MD Nothing to disclose

More information

THERAPEUTICS IN PULMONARY ARTERIAL HYPERTENSION Evidences & Guidelines

THERAPEUTICS IN PULMONARY ARTERIAL HYPERTENSION Evidences & Guidelines THERAPEUTICS IN PULMONARY ARTERIAL HYPERTENSION Evidences & Guidelines Vu Nang Phuc, MD Dinh Duc Huy, MD Pham Nguyen Vinh, MD, PhD, FACC Tam Duc Cardiology Hospital Faculty Disclosure No conflict of interest

More information

National Horizon Scanning Centre. Tadalafil for pulmonary arterial hypertension. October 2007

National Horizon Scanning Centre. Tadalafil for pulmonary arterial hypertension. October 2007 Tadalafil for pulmonary arterial hypertension October 2007 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a

More information

Prostacyclin has potent vasodilatory,

Prostacyclin has potent vasodilatory, Eur Respir Rev 29; 18: 111, 29 34 DOI: 1.1183/95918.11111 CopyrightßERSJ Ltd 29 Inhaled iloprost for the treatment of pulmonary hypertension H. Olschewski ABSTRACT: Prostacyclin and its analogues (prostanoids)

More information

Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension

Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension Eur Respir J 2002; 20: 339 343 DOI: 10.1183/09031936.02.02462001 Printed in UK all rights reserved Copyright #ERS Journals Ltd 2002 European Respiratory Journal ISSN 0903-1936 Intravenous iloprost for

More information

Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostacyclin therapy

Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostacyclin therapy Eur Respir Rev 2009; 18: 114, 253 259 DOI: 10.1183/09059180.00003109 CopyrightßERSJ Ltd 2009 REVIEW Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostacyclin therapy

More information

Role of Combination PAH Therapies

Role of Combination PAH Therapies Role of Combination PAH Therapies Ronald J. Oudiz, MD, FACP, FACC Associate Professor of Medicine, David Geffen School of Medicine at UCLA Director, Liu Center for Pulmonary Hypertension Los Angeles Biomedical

More information

Medical Therapy for Pulmonary Arterial Hypertension* Updated ACCP Evidence-Based Clinical Practice Guidelines

Medical Therapy for Pulmonary Arterial Hypertension* Updated ACCP Evidence-Based Clinical Practice Guidelines CHEST Clinical Practice Guidelines Medical Therapy for Pulmonary Arterial Hypertension* Updated ACCP Evidence-Based Clinical Practice Guidelines David B. Badesch, MD, FCCP; Steven H. Abman, MD; Gerald

More information

Chronic Thromboembolic Pulmonary Hypertention CTEPH

Chronic Thromboembolic Pulmonary Hypertention CTEPH Chronic Thromboembolic Pulmonary Hypertention CTEPH Medical Management Otto Schoch, Prof. Dr. Klinik für Pneumologie und Schlafmedizin Kantonsspital St.Gallen CTEPH: Medical Management Diagnostic aspects

More information

Sildenafil And Atorvastatin Added To Bosentan As Therapy For Pulmonary Hypertension

Sildenafil And Atorvastatin Added To Bosentan As Therapy For Pulmonary Hypertension ISPUB.COM The Internet Journal of Pulmonary Medicine Volume 6 Number 1 Sildenafil And Atorvastatin Added To Bosentan As Therapy For Pulmonary Hypertension M Gomberg-Maitland, M Gulati, V McLaughlin, S

More information

Therapeutic approaches in P(A)H and the new ESC Guidelines

Therapeutic approaches in P(A)H and the new ESC Guidelines Therapeutic approaches in P(A)H and the new ESC Guidelines Jean-Luc Vachiéry, FESC Head Pulmonary Vascular Diseases and Heart Failure Clinic Hôpital Universitaire Erasme Université Libre de Bruxelles Belgium

More information

Effects of Long-Term Bosentan in Children With Pulmonary Arterial Hypertension

Effects of Long-Term Bosentan in Children With Pulmonary Arterial Hypertension Journal of the American College of Cardiology Vol. 46, No. 4, 2005 2005 by the American College of Cardiology Foundation ISSN 0735-1097/05/$30.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2005.01.066

More information

Ambrisentan Therapy for Pulmonary Arterial Hypertension

Ambrisentan Therapy for Pulmonary Arterial Hypertension Journal of the American College of Cardiology Vol. 46, No. 3, 2005 2005 by the American College of Cardiology Foundation ISSN 0735-1097/05/$30.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2005.04.050

More information

Clinical Policy: Macitentan (Opsumit) Reference Number: ERX.SPMN.88

Clinical Policy: Macitentan (Opsumit) Reference Number: ERX.SPMN.88 Clinical Policy: (Opsumit) Reference Number: ERX.SPMN.88 Effective Date: 07/16 Last Review Date: 06/16 Coding Implications Revision Log See Important Reminder at the end of this policy for important regulatory

More information

Oral Therapies for Pulmonary Arterial Hypertension

Oral Therapies for Pulmonary Arterial Hypertension Oral Therapies for Pulmonary Arterial Hypertension Leslie Wooten, PharmD PGY2 Internal Medicine Pharmacy Resident University of Cincinnati Medical Center April 30 th, 2018 Objectives Pharmacist Objectives

More information

Effective Strategies and Clinical Updates in Pulmonary Arterial Hypertension

Effective Strategies and Clinical Updates in Pulmonary Arterial Hypertension Effective Strategies and Clinical Updates in Pulmonary Arterial Hypertension Hap Farber Director, Pulmonary Hypertension Center Boston University School of Medicine Disclosures 1) Honoria: Actelion, Gilead,

More information

Anjali Vaidya, MD, FACC, FASE, FACP Associate Director, Pulmonary Hypertension, Right Heart Failure, Pulmonary Thromboendarterectomy Program Advanced

Anjali Vaidya, MD, FACC, FASE, FACP Associate Director, Pulmonary Hypertension, Right Heart Failure, Pulmonary Thromboendarterectomy Program Advanced Anjali Vaidya, MD, FACC, FASE, FACP Associate Director, Pulmonary Hypertension, Right Heart Failure, Pulmonary Thromboendarterectomy Program Advanced Heart Failure & Cardiac Transplant Temple University

More information

Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension

Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension Journal of the American College of Cardiology Vol. 54, No. 21, 2009 2009 by the American College of Cardiology Foundation ISSN 0735-1097/09/$36.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2009.07.033

More information

Pharmacy Management Drug Policy

Pharmacy Management Drug Policy SUBJECT: POLICY NUMBER: PHARMACY-42 EFFECTIVE DATE: 6/2005 LAST REVIEW DATE: 10/1/2018 If the member s subscriber contract excludes coverage for a specific service or prescription drug, it is not covered

More information

1. Phosphodiesterase Type 5 Enzyme Inhibitors: Sildenafil (Revatio), Tadalafil (Adcirca)

1. Phosphodiesterase Type 5 Enzyme Inhibitors: Sildenafil (Revatio), Tadalafil (Adcirca) This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutic

More information

Cardiac Catheterization is Unnecessary in the Evaluation of Patients with Pulmonary Hypertension: CON

Cardiac Catheterization is Unnecessary in the Evaluation of Patients with Pulmonary Hypertension: CON Cardiac Catheterization is Unnecessary in the Evaluation of Patients with Pulmonary Hypertension: CON Dunbar Ivy, MD The Children s s Hospital Heart Institute 1 Diagnostic Evaluation: Right Heart Cardiac

More information

Clinical Policy: Ambrisentan (Letairis) Reference Number: ERX.SPMN.84 Effective Date: 07/16

Clinical Policy: Ambrisentan (Letairis) Reference Number: ERX.SPMN.84 Effective Date: 07/16 Clinical Policy: (Letairis) Reference Number: ERX.SPMN.84 Effective Date: 07/16 Last Review Date: 06/16 Revision Log See Important Reminder at the end of this policy for important regulatory and legal

More information

Πνευμονική Υπέρταση Ι.Ε. ΚΑΝΟΝΙΔΗΣ

Πνευμονική Υπέρταση Ι.Ε. ΚΑΝΟΝΙΔΗΣ Πνευμονική Υπέρταση Ι.Ε. ΚΑΝΟΝΙΔΗΣ PH is defined as PAPm 25 mm Hg at rest The general definition of PH remains unchanged Most of the relevant epidemiological and therapeutic studies have used the 25 mm

More information

*Division of Pulmonary, Sleep, and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA

*Division of Pulmonary, Sleep, and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA The Relationship between NO Pathway Biomarkers and Response to Riociguat in the RESPITE Study of Patients with PAH Not Reaching Treatment Goals with Phosphodiesterase 5 Inhibitors James R Klinger,* Raymond

More information

Survival in patients with pulmonary arterial hypertension treated with first-line bosentan

Survival in patients with pulmonary arterial hypertension treated with first-line bosentan European Journal of Clinical Investigation (2006) 36 (Suppl. 3), 10 15 Blackwell Publishing Ltd Survival in patients with pulmonary arterial hypertension treated with first-line bosentan V. V. McLaughlin

More information

Dr. Md. Rajibul Alam Prof. of Medicine Dinajpur Medical college

Dr. Md. Rajibul Alam Prof. of Medicine Dinajpur Medical college Dr. Md. Rajibul Alam Prof. of Medicine Dinajpur Medical college PULMONARY HYPERTENSION Difficult to diagnose early Because Not detected during routine physical examination and Even in advanced cases symptoms

More information

Combination therapy in the treatment of pulmonary arterial hypertension 2015 update

Combination therapy in the treatment of pulmonary arterial hypertension 2015 update Journal of Rare Cardiovascular Diseases 2015; 2 (4): 103 107 www.jrcd.eu REVIEW ARTICLE Rare diseases of pulmonary circulation Combination therapy in the treatment of pulmonary arterial hypertension 2015

More information

The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension

The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension REVIEW 6MWD IN PAH TRIALS The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension Sean Gaine 1 and Gérald Simonneau 2 Affiliations: 1 National Pulmonary Hypertension

More information

IV PGI2 vs. Inhaled PGI2 in chronic lung disease

IV PGI2 vs. Inhaled PGI2 in chronic lung disease Inhaled Therapies for PAH Erika Berman Rosenzweig, MD Associate Professor of Clinical Pediatrics (in Medicine) Director, Pulmonary Hypertension Center Columbia University Medical Center Disclosures Has

More information

Clinical Commissioning Policy: Selexipag in the treatment of Pulmonary Arterial Hypertension

Clinical Commissioning Policy: Selexipag in the treatment of Pulmonary Arterial Hypertension Clinical Commissioning Policy: Selexipag in the treatment of Pulmonary Arterial Hypertension Reference: NHS England: 16017/P NHS England INFORMATION READER BOX Directorate Medical Operations and Information

More information

National Horizon Scanning Centre. Oral and inhaled treprostinil for pulmonary arterial hypertension: NYHA class III. April 2008

National Horizon Scanning Centre. Oral and inhaled treprostinil for pulmonary arterial hypertension: NYHA class III. April 2008 Oral and inhaled treprostinil for pulmonary arterial hypertension: NYHA class April 2008 This technology summary is based on information available at the time of research and a limited literature search.

More information

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE. Health Technology Appraisal. Drugs for the treatment of pulmonary arterial hypertension

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE. Health Technology Appraisal. Drugs for the treatment of pulmonary arterial hypertension NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Health Technology Appraisal Drugs for the treatment of Draft remit / appraisal objective: Draft scope To appraise the clinical and cost effectiveness

More information

Selection of Infusion Prostacyclin Therapy in Pulmonary Arterial Hypertension: Not Just a Last Resort

Selection of Infusion Prostacyclin Therapy in Pulmonary Arterial Hypertension: Not Just a Last Resort Selection of Infusion Prostacyclin Therapy in Pulmonary Arterial Hypertension: Not Just a Last Resort Robert Schilz, DO, PhD, FCCP Medical Director, Lung Transplantation and Pulmonary Vascular Disease

More information

MAURICE BEGHETTI, MARIUS M. HOEPER, DAVID G. KIELY, JOERN CARLSEN, BARBARA SCHWIERIN, ELEANOR S. SEGAL, AND MARC HUMBERT

MAURICE BEGHETTI, MARIUS M. HOEPER, DAVID G. KIELY, JOERN CARLSEN, BARBARA SCHWIERIN, ELEANOR S. SEGAL, AND MARC HUMBERT 0031-3998/08/6402-0200 PEDIATRIC RESEARCH Copyright 2008 International Pediatric Research Foundation, Inc. Vol. 64, No. 2, 2008 Printed in U.S.A. Safety Experience With Bosentan in 146 Children 2 11 Years

More information

Pulmonary arterial hypertension (PAH) is a. The use of combination therapy in pulmonary arterial hypertension: new developments REVIEW

Pulmonary arterial hypertension (PAH) is a. The use of combination therapy in pulmonary arterial hypertension: new developments REVIEW Eur Respir Rev 2009; 18: 113, 148 153 DOI: 10.1183/09059180.00003809 CopyrightßERSJ Ltd 2009 REVIEW The use of combination therapy in pulmonary arterial hypertension: new developments N. Galiè*, L. Negro*

More information

Pharmacy Medical Necessity Guidelines: Pulmonary Hypertension Medications

Pharmacy Medical Necessity Guidelines: Pulmonary Hypertension Medications Pharmacy Medical Necessity Guidelines: Pulmonary Hypertension Medications Effective: January 15, 2018 Prior Authorization Required Type of Review Care Management Not Covered Type of Review Clinical Review

More information

TREPROSTINIL Generic Brand HICL GCN Exception/Other TREPROSTINIL REMODULIN 23650

TREPROSTINIL Generic Brand HICL GCN Exception/Other TREPROSTINIL REMODULIN 23650 Generic Brand HICL GCN Exception/Other TREPROSTINIL REMODULIN 23650 SODIUM TREPROSTINIL TYVASO 36537 36539 36541 TREPROSTINIL ORENITRAM 40827 **Please use the criteria for the specific drug requested**

More information

Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2

Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2 Eur Respir J 24; 24: 353 359 DOI: 1.1183/931936.4.2844 Printed in UK all rights reserved Copyright #ERS Journals Ltd 24 European Respiratory Journal ISSN 93-1936 Combination of bosentan with epoprostenol

More information

PULMONARY ARTERIAL HYPERTENSION AGENTS

PULMONARY ARTERIAL HYPERTENSION AGENTS Approvable Criteria: PULMONARY ARTERIAL HYPERTENSION AGENTS Brand Name Generic Name Length of Authorization Adcirca tadalafil Calendar Year Adempas riociguat Calendar Year Flolan epoprostenol sodium Calendar

More information

MACITENTAN DEVELOPMENT IN CHILDREN WITH PULMONARY HYPERTENSION (PAH)

MACITENTAN DEVELOPMENT IN CHILDREN WITH PULMONARY HYPERTENSION (PAH) MACITENTAN DEVELOPMENT IN CHILDREN WITH PULMONARY HYPERTENSION (PAH) ORPHAN DRUG AND RARE DISEASE 11 MAY 2017 Catherine Lesage, MD, Pediatrics Program Head, Actelion Copyright AGENDA Pulmonary Arterial

More information

2012 CADTH Symposium. April 2012

2012 CADTH Symposium. April 2012 2012 CADTH Symposium Using Mixed Treatment Comparisons to compare Oral Treatments for Pulmonary Arterial Hypertension and Inform Policy Decisions by a Public Drug Plan April 2012 Objective of this Presentation

More information

Clinical Policy: Treprostinil (Orenitram, Remodulin, Tyvaso) Reference Number: ERX.SPA.36 Effective Date:

Clinical Policy: Treprostinil (Orenitram, Remodulin, Tyvaso) Reference Number: ERX.SPA.36 Effective Date: Clinical Policy: (Orenitram, Remodulin, Tyvaso) Reference Number: ERX.SPA.36 Effective Date: 07.01.16 Last Review Date: 02.18 Revision Log See Important Reminder at the end of this policy for important

More information

Review of bosentan in the management of pulmonary arterial hypertension

Review of bosentan in the management of pulmonary arterial hypertension REVIEW Review of bosentan in the management of pulmonary arterial hypertension Eli Gabbay 1 John Fraser 2 Keith McNeil 3 1 Western Australian Lung Transplant Unit and Pulmonary Hypertension Service, Royal

More information

Clinical Policy: Treprostinil (Orenitram, Remodulin, Tyvaso) Reference Number: ERX.SPA.36 Effective Date:

Clinical Policy: Treprostinil (Orenitram, Remodulin, Tyvaso) Reference Number: ERX.SPA.36 Effective Date: Clinical Policy: (Orenitram, Remodulin, Tyvaso) Reference Number: ERX.SPA.36 Effective Date: 07.01.16 Last Review Date: 02.19 Revision Log See Important Reminder at the end of this policy for important

More information

Progress in PAH. Gerald Simonneau

Progress in PAH. Gerald Simonneau Progress in PAH Gerald Simonneau National Reference center for Pulmonary Hypertension Bicetre University Hospital, INSERM U 999 Paris-Sud University Le Kremlin Bicêtre France Clinical Classification of

More information

Advanced Therapies for Pharmocological Treatment of Pulmonary Arterial Hypertension. Original Policy Date

Advanced Therapies for Pharmocological Treatment of Pulmonary Arterial Hypertension. Original Policy Date MP 5.01.07 Advanced Therapies for Pharmocological Treatment of Pulmonary Arterial Hypertension Medical Policy Section Prescription Drug Issue 12:2013 Original Policy Date 12:2013 Last Review Status/Date

More information

Efficacy and Limitations of Continuous Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension in Japanese Children

Efficacy and Limitations of Continuous Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension in Japanese Children Circ J 2007; 71: 1785 1790 Efficacy and Limitations of Continuous Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension in Japanese Children Tomotaka Nakayama, MD; Hiromitsu Shimada,

More information

Pulmonary Arterial Hypertension (PAH) Treatments

Pulmonary Arterial Hypertension (PAH) Treatments Care1st Health Plan Arizona, Inc. Easy Choice Health Plan Harmony Health Plan of Illinois Missouri Care Ohana Health Plan, a plan offered by WellCare Health Insurance of Arizona OneCare (Care1st Health

More information

Pulmonary arterial hypertension (PAH) is a

Pulmonary arterial hypertension (PAH) is a Eur Respir J 2007; 30: 1103 1110 DOI: 10.1183/09031936.00042107 CopyrightßERS Journals Ltd 2007 A USA-based registry for pulmonary arterial hypertension: 1982 2006 T. Thenappan, S.J. Shah, S. Rich and

More information

The New England Journal of Medicine LONG-TERM TREATMENT OF PRIMARY PULMONARY HYPERTENSION WITH AEROSOLIZED ILOPROST, A PROSTACYCLIN ANALOGUE.

The New England Journal of Medicine LONG-TERM TREATMENT OF PRIMARY PULMONARY HYPERTENSION WITH AEROSOLIZED ILOPROST, A PROSTACYCLIN ANALOGUE. LONG-TERM TREATMENT OF PRIMARY PULMONARY HYPERTENSION WITH AEROSOLIZED ILOPROST, A PROSTACYCLIN ANALOGUE MARIUS M. HOEPER, M.D., MICHAEL SCHWARZE, STEFAN EHLERDING, ANGELIKA ADLER-SCHUERMEYER, R.N., EDDA

More information

Update in Pulmonary Arterial Hypertension

Update in Pulmonary Arterial Hypertension Update in Pulmonary Arterial Hypertension Michael J Sanley, MD April 12, 2018 Disclosures I have nothing to disclose 2 1 Case Presentation 67 yo male with atrial fibrillation, CLL on IVIG, presents with

More information

Objectives. Disclosures Oral Therapies for Children with Pulmonary Hypertensive Vascular Disease

Objectives. Disclosures Oral Therapies for Children with Pulmonary Hypertensive Vascular Disease Disclosures Oral Therapies for Children with Pulmonary Hypertensive Vascular Disease Erika Berman Rosenzweig, MD Director, Pulmonary Hypertension Center Associate Professor of Clinical Pediatrics (in Medicine)

More information

Updates in Pulmonary Hypertension Pharmacotherapy. Ziad Sadik PharmD BCPS

Updates in Pulmonary Hypertension Pharmacotherapy. Ziad Sadik PharmD BCPS Updates in Pulmonary Hypertension Pharmacotherapy Ziad Sadik PharmD BCPS Disclosure Information I have no financial relationship to disclose AND I will not discuss off label use and/or investigational

More information

Scottish Medicines Consortium

Scottish Medicines Consortium Scottish Medicines Consortium sildenafil, 20mg (as citrate) tablets (Revatio ) No. (596/10) Pfizer Ltd 15 January 2010 The Scottish Medicines Consortium (SMC) has completed its assessment of the above

More information

4/14/2010. Pulmonary Hypertension: An Update. Tim Williamson, MD, FCCP. University of Kansas Hospital. Normal Physiology

4/14/2010. Pulmonary Hypertension: An Update. Tim Williamson, MD, FCCP. University of Kansas Hospital. Normal Physiology Pulmonary Hypertension: An Update Tim Williamson, MD, FCCP Director, Pulmonary Vascular Program University of Kansas Hospital Normal Physiology 1 Pulmonary Perfusion 101 High Pressure Low Pressure Pulmonary

More information

Prior Authorization Required Type of Review Care Management Not Covered Type of Review Clinical Review

Prior Authorization Required Type of Review Care Management Not Covered Type of Review Clinical Review Pharmacy Medical Necessity Guidelines: Effective: July 11, 2017 Prior Authorization Required Type of Review Care Management Not Covered Type of Review Clinical Review Pharmacy (RX) or Medical (MED) Benefit

More information

Serum N-Terminal Brain Natriuretic Peptide as a Prognostic Parameter in Patients With Pulmonary Hypertension*

Serum N-Terminal Brain Natriuretic Peptide as a Prognostic Parameter in Patients With Pulmonary Hypertension* CHEST Serum N-Terminal Brain Natriuretic Peptide as a Prognostic Parameter in Patients With Pulmonary Hypertension* Anna Fijalkowska, MD; Marcin Kurzyna, MD; Adam Torbicki, MD; Grzegorz Szewczyk, MD; Michał

More information

Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil

Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil Eur Respir J 6; 28: 1195 13 DOI:.1183/931936.6.4446 CopyrightßERS Journals Ltd 6 Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil R.J. Barst*, N. Galie

More information

Real-world experience with riociguat in CTEPH

Real-world experience with riociguat in CTEPH Real-world experience with riociguat in CTEPH Matthias Held Center of Pulmonary Hypertension and Pulmonary Vascular Disease, Medical Mission Hospital, Würzburg, Germany Tuesday, 29 September ERS International

More information

Pulmonary Hypertension Perioperative Management

Pulmonary Hypertension Perioperative Management Pulmonary Hypertension Perioperative Management Bruce J Leone, MD Professor of Anesthesiology Chief, Neuroanesthesiology Vice Chair for Academic Affairs Mayo Clinic Jacksonville, Florida Introduction Definition

More information

Prognostic value of echocardiographic parameters in patients with pulmonary arterial hypertension (PAH) treated with targeted therapies

Prognostic value of echocardiographic parameters in patients with pulmonary arterial hypertension (PAH) treated with targeted therapies Prognostic value of echocardiographic parameters in patients with pulmonary arterial hypertension (PAH) treated with targeted therapies E. Beciani, M. Palazzini, C. Bachetti, F. Sgro, E. Conficoni, E.

More information

Increasing knowledge about the pathophysiology

Increasing knowledge about the pathophysiology Eur Respir Rev 27; 16: 12, 13 18 DOI: 1.1183/95918.124 CopyrightßERSJ Ltd 27 Dual endothelin receptor antagonism: setting standards in PAH M. Humbert ABSTRACT: Endothelin (ET) has emerged as a key mediator

More information

Pulmonary Hypertension: Another Use for Viagra

Pulmonary Hypertension: Another Use for Viagra Pulmonary Hypertension: Another Use for Viagra Kathleen Tong, MD Director, Heart Failure Program Assistant Clinical Professor University of California, Davis Disclosures I have no financial conflicts A

More information

ADVANCED THERAPIES FOR PHARMACOLOGICAL TREATMENT OF PULMONARY HYPERTENSION

ADVANCED THERAPIES FOR PHARMACOLOGICAL TREATMENT OF PULMONARY HYPERTENSION Status Active Medical and Behavioral Health Policy Section: Medicine Policy Number: II-107 Effective Date: 04/21/2014 Blue Cross and Blue Shield of Minnesota medical policies do not imply that members

More information

Riociguat for chronic thromboembolic pulmonary hypertension

Riociguat for chronic thromboembolic pulmonary hypertension Riociguat for chronic thromboembolic pulmonary hypertension This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a

More information

Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome

Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome Kenji MIWA, 1 MD, Takashi MATSUBARA, 1 MD, Yoshihide UNO, 1 MD, Toshihiko YASUDA,

More information

Pulmonary Arterial Hypertension: The Approach to Management in 2019

Pulmonary Arterial Hypertension: The Approach to Management in 2019 Pulmonary Arterial Hypertension: The Approach to Management in 2019 Munir S. Janmohamed M.D. FACC Medical Director Mechanical Circulatory Support/Heart Failure Program Mercy General Hospital/Mercy Medical

More information

Pulmonary Hypertension. Pulmonary Arterial Hypertension Diagnosis, Impact and Outcomes

Pulmonary Hypertension. Pulmonary Arterial Hypertension Diagnosis, Impact and Outcomes Pulmonary Hypertension Pulmonary Arterial Hypertension Diagnosis, Impact and Outcomes Pulmonary Arterial Hypertension Disease of small pulmonary arteries Characteristic changes Medial hypertrophy Intimal

More information

Paediatric addendum to CHMP guideline on the clinical investigations of medicinal products for the treatment of pulmonary arterial hypertension

Paediatric addendum to CHMP guideline on the clinical investigations of medicinal products for the treatment of pulmonary arterial hypertension 5 December 2011 EMA/CHMP/213972/2010 Committee for Medicinal Products for Human use (CHMP) Paediatric addendum to CHMP guideline on the clinical investigations of medicinal products for the treatment of

More information

(CHEST 2004; 126:35S 62S)

(CHEST 2004; 126:35S 62S) Medical Therapy For Pulmonary Arterial Hypertension* ACCP Evidence-Based Clinical Practice Guidelines David B. Badesch, MD, FCCP; Steve H. Abman, MD; Gregory S. Ahearn, MD; Robyn J. Barst, MD; Douglas

More information

Does Tadalafil Improve Exercise Capacitance in Patients over 12 Years Old with Pulmonary Hypertension?

Does Tadalafil Improve Exercise Capacitance in Patients over 12 Years Old with Pulmonary Hypertension? Philadelphia College of Osteopathic Medicine DigitalCommons@PCOM PCOM Physician Assistant Studies Student Scholarship Student Dissertations, Theses and Papers 2012 Does Tadalafil Improve Exercise Capacitance

More information

Pulmonary Arterial Hypertension - Overview

Pulmonary Arterial Hypertension - Overview Pulmonary Arterial Hypertension - Overview J. Shaun Smith, MD Co-Director, Pulmonary Vascular Disease Program Assistant Professor of Medicine Division of Pulmonary, Critical Care and Sleep Medicine The

More information

Pulmonary Arterial Hypertension - Overview

Pulmonary Arterial Hypertension - Overview Pulmonary Arterial Hypertension - Overview J. Shaun Smith, MD Co-Director, Pulmonary Vascular Disease Program Assistant Professor of Medicine Division of Pulmonary, Critical Care and Sleep Medicine The

More information

TITLE: Combination Therapy for Pulmonary Arterial Hypertension: A Review of the Clinical Effectiveness

TITLE: Combination Therapy for Pulmonary Arterial Hypertension: A Review of the Clinical Effectiveness TITLE: Combination Therapy for Pulmonary Arterial Hypertension: A Review of the Clinical Effectiveness DATE: 01 December 2011 CONTEXT AND POLICY ISSUES Pulmonary arterial hypertension (PAH) is a chronic

More information

Clinical Policy: Treprostinil (Orenitram, Remodulin, Tyvasco) Reference Number: CP.PHAR.199

Clinical Policy: Treprostinil (Orenitram, Remodulin, Tyvasco) Reference Number: CP.PHAR.199 Clinical Policy: (Orenitram, Remodulin, Tyvasco) Reference Number: CP.PHAR.199 Effective Date: 03/16 Last Review Date: 03/17 See Important Reminder at the end of this policy for important regulatory and

More information

Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension

Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension Journal of the American College of Cardiology Vol. 51, No. 2, 2008 2008 by the American College of Cardiology Foundation ISSN 0735-1097/08/$34.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2007.09.031

More information

Referral Forms for TYVASO and REMODULIN

Referral Forms for TYVASO and REMODULIN Referral Forms for TYVASO and REMODULIN HOW TO GET STARTED Tyvaso and Remodulin are available only through select Specialty Pharmacy Services (SPS) providers. Follow these 5 simple steps to complete each

More information

Advancements In pulmonary arterial hypertension treatment

Advancements In pulmonary arterial hypertension treatment Boston University OpenBU Theses & Dissertations http://open.bu.edu Boston University Theses & Dissertations 2017 Advancements In pulmonary arterial hypertension treatment Bains, Ashank https://hdl.handle.net/2144/26562

More information

Updates on Pulmonary Hypertension Treatment

Updates on Pulmonary Hypertension Treatment Updates on Pulmonary Hypertension Treatment Dane Mellgren, PharmD PGY-1 Pharmacy Practice Resident Hennepin County Medical Center 04/27/18 Disclosure I have no disclosures to be made regarding the content

More information

Abstract Book. Inspiring Approaches to Clinical Challenges in Pulmonary Hypertension

Abstract Book. Inspiring Approaches to Clinical Challenges in Pulmonary Hypertension Inspiring Approaches to Clinical Challenges in Pulmonary Hypertension Abstract Book A symposium sponsored by Bayer Schering Pharma at ERS 2008 Annual Congress www.ventavis.com Welcome Dear Colleague, It

More information

Serial Plasma Brain Natriuretic Peptide Testing in Clinical Management of Pulmonary Arterial Hypertension

Serial Plasma Brain Natriuretic Peptide Testing in Clinical Management of Pulmonary Arterial Hypertension Original Article Acta Cardiol Sin 2009;25:147 53 Pulmonary Hypertension Serial Plasma Brain Natriuretic Peptide Testing in Clinical Management of Pulmonary Arterial Hypertension Wan-Jing Ho, 1 Tsu-Shiu

More information

ELIGIBILITY CRITERIA FOR PULMONARY ARTERIAL HYPERTENSION THERAPY

ELIGIBILITY CRITERIA FOR PULMONARY ARTERIAL HYPERTENSION THERAPY ELIGIBILITY CRITERIA FOR PULMONARY ARTERIAL HYPERTENSION THERAPY Contents Eligibility criteria for Pulmonary Arterial Hypertension therapy...2-6 Initial Application for funding of Pulmonary Arterial Hypertension

More information

Pulmonary arterial hypertension. Pulmonary arterial hypertension: newer therapies. Definition of PH 12/18/16. WHO Group classification of PH

Pulmonary arterial hypertension. Pulmonary arterial hypertension: newer therapies. Definition of PH 12/18/16. WHO Group classification of PH Pulmonary arterial hypertension Pulmonary arterial hypertension: newer therapies Ramona L. Doyle, MD Clinical Professor of Medicine, UCSF Attending Physician UCSF PH Clinic Definition and classification

More information

Clinical Policy: Bosentan (Tracleer) Reference Number: CP.PHAR.191

Clinical Policy: Bosentan (Tracleer) Reference Number: CP.PHAR.191 Clinical Policy: (Tracleer) Reference Number: CP.PHAR.191 Effective Date: 03/16 Last Review Date: 03/17 Coding Implications Revision Log See Important Reminder at the end of this policy for important regulatory

More information

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension Eur Respir J 2002; 20: 1037 1049 DOI: 10.1183/09031936.02.05542002 Printed in UK all rights reserved Copyright #ERS Journals Ltd 2002 European Respiratory Journal ISSN 0903-1936 SERIES 0ADVANCES IN PATHOBIOLOGY,

More information