Efficacy Of Bosentan Research Articles

Current Status of Endothelin Receptor Antagonists in Pulmonary Arterial Hypertension: A Combined Study Results and Pharmacology-Based Review.

Pulmonary arterial hypertension (PAH) affects a wide range of people globally and has a poor prognosis despite many advancements in available treatment options. Among the available treatments, endothelin receptor antagonists (ERA) are among the most widely used drugs. These drugs have been evaluated in scientific trials. We included free full texts in the English language from the last ten years and reviewed them. We are writing this review to amalgamate the pharmacological aspects and the previous studies on ERAs to demonstrate a comprehensive overview of the current status of ERAs for PAH treatment. We focused on the structure, pharmacodynamics, pharmacokinetics, and efficacy and safety of the three most widely used ERAs: Bosentan, Ambrisentan, and Macitentan. These drugs have different receptor affinities, bioavailability, excretion routes, and different levels of safety profiles. There are three available studies, the RCT, the ARIES series, and the SERAPHIN studies, for assessing the safety and efficacy of Bosentan, Ambrisentan, and Macitentan, respectively. All the studies and some additional studies for combination therapy have proven all three drugs effective in treating PAH. The side effects (SE) varied from headache and hepatic enzyme elevation to worsening the PAH status of varied severities. Although these studies provided valuable insight into the role of ERAs, there is still enough scope for more studies on ERAs, both as monotherapy and combination therapy for PAH.

PULMONARY HYPERTENSION STILL AN ‘ORPHAN LUNG DISEASE’ IN PAKISTAN

In our country when it comes to diagnosis and treatment of Pulmonary Hypertension (PH) especially Pulmonary Arterial Hypertension (PAH), it seems that it is still an Orphan Lung disease. Whether it is data about its prevalence in our country, available diagnostic services or treatment options, one may easily feel the scarcity in all mentioned areas.
 Most current classification of PH, categorizes it into 5 groups.1 However this categorization requires availability of diagnostic tools especially right heart catheterization data to classify and know the severity of PH and to offer targeted treatment to patients who belong to group 1 PH i.e. Pulmonary Arterial Hypertension (PAH).
 Studies done about PH prevalence in Pakistan have mainly focused on data in selected patients group e.g. in patients with Chronic Obstructive Pulmonary Diseases (COPD) or Systemic Lupus Erythematosus (SLE).2,3 All of these studies relied on diagnosis without using the diagnostic bench mark i.e. Right heart catheterization. Moreover, effects of targeted treatment for PAH have also been studied only in selected group of patients e.g. COPD.4,5
 While above work by the learned colleagues has to be appreciated, it emphasizes the need to,
 
 Spread the awareness about PH more so to reduce inadvertent use of targeted treatment which may prove detrimental outside group 1 PH and should only be considered at specialized centers.
 Develop specialized centers with required diagnostic services especially Lung functional and anatomical evaluation and Right heart catheterization.
 Establish PH registries (at least one in each province) which can play a vital role to collect data and ensure effective evidence based patient management.
 
 This may be an uphill task however the right direction to move forward.
 
 REFERENCES
 
 Simonneau G, Montani D, David SC, Christopher PD, Michael AG, Michael K, at el. Paul G. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913.
 Amir S, Azmat A, Raza U, Hamid N, Zafar I, Shahida N, at el. Frequency of Pulmonary Hypertension in COPD patients. Pak J Chest Med. 2017;23(4):144-50.
 Sadia A, Aflak R, Tafazzul H, Ahmed A. Frequency and predictors of Pulmonary Hypertension in patients with SLE. Pak J Med Sci. 2019;35(1):86-9.
 Nasir H, Faisal F, Kausar R, Saadia A, Anjum N, Shafi K, at el. Efficacy of bosentan in the treatment of pulmonary hypertension; a prospective study focusing on safety and efficacy in patients with COPD. J Lung Pulm Respir Res. 2018;5(2):67-72.
 Sharieff S. Effect of sildenafil in primary pulmonary hypertension. Pak J Med Sci. 2007;23(2):264.

Efficacy of bosentan in the treatment of pulmonary hypertension; a prospective study focusing on safety and efficacy in patients with COPD

Efficacy of bosentan in the treatment of pulmonary hypertension; a prospective study focusing on safety and efficacy in patients with COPD

Efficacy of bosentan in the treatment of Raynaud’s phenomenon in patients with systemic sclerosis never treated with prostanoids

The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud's phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud's phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126). The Raynaud's condition score showed a statistically significant improvement (Δ-1.4, P=0.0279), as did the visual analog pain scale (Δ-1.5, P=0.0016) at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud's phenomenon for patients where prostanoids therapy is contraindicated or refused.

A randomized open label study comparing first-line treatment with bosentan or sildenafil in Pulmonary Arterial Hypertension (PAH)

Background: The efficacy of Bosentan (B) and Sildenafil (S) for the treatment of PAH appears to be similar according to specific randomized controlled trials. Limited data is available on the direct comparison between these two drugs. Objectives: to compare short-term hemodynamic and functional data and long-term outcome of PAH patients treated with first-line B (125 mg bid) or first-line S therapy (20 mg tid). Methods: From November 2006 to January 2013 consecutive naive patients were randomized to receive B or S. Short-term analysis was made by clinical assessment, 6-minute walk test [6MWT] and right-heart catheterization [RHC] at baseline and after 4.1±1.2 months of therapy. In the long-term comparison we evaluated time to clinical worsening defined as the time from randomization to the first occurrence of death (all causes), hospitalization for worsening of PAH or addition of any specific therapy for PAH. Statistical analysis: Wilcoxon-Mann-Whitney test and Kaplan-Meier method. Results: 205 PAH patients were randomized: 100 to the B group (mean age 55±17; 41% idiopathic-PAH [IPAH]; 24% PAH associated with congenital heart disease [PAH-CHD]; 18% PAH associated with connective tissue disease [PAH-CTD]; 11% PAH associated with portal hypertension [PoPAH]; 6% PAH associated with HIV infection [PAH-HIV]) and 105 to the S group (mean age 53±17; 40% IPAH; 20% PAH-CHD; 21% PAH-CTD; 14% PO-PAH; 5% PAH-HIV). Twenty patients (20%) in the B group and 13 (12%) in the S group did not complete the short term evaluation because of death, adverse events, protocol violations, lack of hemodynamic data or were lost to follow-up. Eighty patients in the B group and 92 in the S group completed the short term study; no statistically significant differences were found in hemodynamics and 6MWT median percent changes among the two treatments. In the long-term study the mean duration of follow up was 26±18 months. The event-free survival estimates at 1, 2 and 3 years were 64%, 51% and 41% in B group and 70%, 60% and 47% in S group (P=0.366), respectively. At 1, 2, and 3 years 81%, 72% and 61% patients in B group and 83%, 73% and 64% in S group (P=0.852) had no hospitalizations or mortality for all causes. The overall survival estimates at 1, 2 and 3 years were 89%, 79% and 71% in B group and 90%, 86% and 81% in S group (P=0.287), respectively. Conclusions: Short and long term comparison between first line treatment with S or B did not show statistically significant differences in clinical, exercise capacity, hemodynamic and outcome parameters.

The clinical efficay of bosentan for idiopathic pulmonary arterial hypertension

Objective To explore the efficacy of bosentan in the treatment of idiopathic pulmonary arterial hypertension ( IPAH ).Methods 45 patients with IPAH were randomly assigned to study group ( 23 patients ) or control group ( 22 patients ).Both groups received conventional therapies and the study group was administered oral bosentan additionally.The efficacy was then analyzed in the two groups.Results 14 days after treatment,levels of PaO2 and 6MWD were higher whereas levels of PaCO2 and PAP were lower in the study group than in the control group [( 81 ± 3.7 )mmHg ( 1 mm Hg=0.133 kPa ) vs.( 57.0 ± 3.9 ) mm Hg and ( 331.0 ± 81.2 ) m vs.( 263.0 ± 58.9 ) m,and ( 43.0 ± 5.9 ) mmHg vs.( 66.0 ± 7.2 ) mm Hg and ( 63.0 ± 17.1 )mm Hg vs.( 78.0 ± 16.7 ) mm Hg; P ＜ 0.05 for all comparisons].Conclusions Oral bosentan is efficacious in the treatment of idiopathic pulmonary arterial hypertension,significantly reducing high pressure of pulmonary artery. Key words: Bosentan; Idiopathic pulmonary arterial hypertension

Long-term efficacy of bosentan in treatment of pulmonary arterial hypertension in children

Long-term efficacy of bosentan in treatment of pulmonary arterial hypertension in children

Safety and Efficacy of Bosentan in Combination With Sildenafil in PAH Patients Who Experience Inadequate Clinical Response to Monotherapy: The COMPASS-3 Study

Safety and Efficacy of Bosentan in Combination With Sildenafil in PAH Patients Who Experience Inadequate Clinical Response to Monotherapy: The COMPASS-3 Study

Outcome of Pediatric Patients With Pulmonary Arterial Hypertension in the Era of New Medical Therapies

Little is known about the effects of "second-generation drugs" (prostanoids, endothelin receptor antagonists, 5-phosphodiesterase inhibitors) in children with pulmonary arterial hypertension (PAH). This study describes the outcome of a national cohort of children with PAH in an era when these drugs became available. From 1993 to 2008, 52 consecutive children with idiopathic PAH (n = 29) or systemic-to-pulmonary shunt-associated PAH (n = 23) underwent baseline and follow-up assessments. Treatment was initiated depending on functional class, acute pulmonary vasoreactivity response, and drug availability. Observed survival was evaluated depending on time of diagnosis in relation to second-generation drug availability and subsequently compared to calculated predicted survival. Children for whom second-generation drugs were available had improved survival compared to their predicted survival (1-, 3-, and 5-year survival rates 93%, 83%, and 66% vs 79%, 61%, and 50%, respectively). However, this improved survival was observed only in patients for whom second-generation drugs became available during their disease course. No improved survival was observed in patients for whom drugs were available already at diagnosis. Baseline variables associated with decreased survival included higher functional class, higher pulmonary-to-systemic arterial pressure ratio, lower cardiac index, and higher serum levels of N-terminal pro-brain natriuretic peptide and uric acid. After start of second-generation drugs, functional class, 6-minute walking distance, and N-terminal pro-brain natriuretic peptide improved but gradually decreased after longer follow-up. In conclusion, survival of pediatric PAH seemed improved since the introduction of second-generation drugs only in selected patients for whom these drugs became available during their disease course. Start of second-generation drugs initially induced clinical improvements, but these effects decreased after longer follow-up.

Efficacy of Bosentan in Digital Ischemic Ulcers

Thromboangiitis obliterans (also known as Buerger's disease) is an inflammatory vascular disorder that affects small and medium-sized arteries and veins in the extremities. There is no specific treatment and the only effective intervention is absolute cessation of tobacco use. Endothelial dysfunction appears to be of relevance to this condition and a report has even found that high serum levels of endothelin correlate with the presence of necrosis. We report two cases of digital necrosis showing a very satisfactory response to treatment with bosentan, a dual endothelin receptor antagonist.

Dual endothelin receptor antagonism: setting standards in PAH

Endothelin (ET) has emerged as a key mediator in the pathophysiology of pulmonary arterial hypertension (PAH). The effects of ET are mediated by its binding to two receptors on endothelial and pulmonary smooth muscle cells: ETA and ETB. Blockade of both these receptors with the oral dual ET receptor antagonist, bosentan, represents an attractive treatment option for these severely compromised patients. The efficacy of bosentan in PAH has been demonstrated in randomised controlled trials in idiopathic PAH, and PAH associated with connective tissue diseases and congenital heart disease. In addition, an open-label study has shown clinical and haemodynamic effects in PAH associated with HIV infection. In these trials, bosentan has been shown to improve haemodynamics, increase functional capacity, improve time to clinical worsening, which is a surrogate marker of survival, and to improve patients' quality of life; in longer-term studies, it has been shown to improve patient outcome. The current article will present these key data from randomised controlled trials on bosentan as well as experiences from everyday clinical practice.

The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, many patients develop a severe progressive small vessel pulmonary arteriopathy that is inaccessible to surgical intervention and is associated with poor survival. The purpose of the present study was to evaluate the medium-term efficacy and safety of the dual endothelin receptor antagonist, bosentan, in inoperable CTEPH. Forty-seven patients with inoperable CTEPH (distal disease or persistent pulmonary hypertension following PEA) underwent evaluation after 1 yr of bosentan therapy. Outcomes included assessment of 6-min walk test (6MWT), haemodynamics and World Health Organization functional classification. Monitoring of serious adverse effects and changes in therapy was undertaken. Patients showed sustained improvements in 6MWT (49+/-8 m), functional classification, cardiac index (+0.2+/-0.07 L.min(-1).m(-2)) and total pulmonary resistance (-139+/-42 dyn.s.cm(-5)). Those patients with persisting pulmonary hypertension following PEA showed the greatest improvement. One-yr survival was 96%, and bosentan was well tolerated with only one patient developing deranged liver function. Although all patients with chronic thromboembolic pulmonary hypertension should be considered for pulmonary endarterectomy, bosentan provides an alternative medical therapy to improve function and delay the progression of this devastating disease in those in whom surgery is not suitable.

Efficacy of Bosentan in a Small Cohort of Adult Patients With Pulmonary Arterial Hypertension Related to Congenital Heart Disease

This study was designed to assess the tolerability and efficacy of the oral endothelin receptor antagonist bosentan in adult patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). Severe PAH in the setting of CHD is a debilitating syndrome for which there are limited treatment options. This is the first long-term study experience in adults reporting on the tolerability and efficacy of therapy with bosentan for this patient population. A 12-month single-center experience with 19 women and 5 men with PAH associated with CHD (79% in New York Heart Association [NYHA] class III) was analyzed. Hemodynamic responses, exercise capacity, and Borg dyspnea index were assessed prior to the administration of bosentan, and again at 3, 6, and 12 months after the study began. Clinical assessments were performed monthly for up to 12 months. The change from baseline was tested using the Wilcoxon pairs test. There was significant improvement in hemodynamics from baseline to 12 months (mean [+/- SD] systolic pulmonary arterial pressure, 99 +/- 30 to 87 +/- 28 mm Hg [p </= 0.001]; mean pulmonary arterial pressure, 60 +/- 18 to 52 +/- 17 mm Hg [p </= 0.001]; mean right atrial pressure, 12 +/- 6 to 8 +/- 5 mm Hg [p </= 0.001]; mean pulmonary vascular resistance, 663 +/- 386 to 504 +/- 307 dyne . s . cm(-5) [p < 0.01]; pulmonary capillary wedge pressure, 15 +/- 5 to 11 +/- 3 mm Hg [p < 0.001]). NYHA functional class also improved from baseline to 12 months (NYHA class I/II range, 17 to 71%; p < 0.001). There was a marginally significant trend toward improvement in the mean 6-min walk test distance at 12 months (299 +/- 85 to 330 +/- 95 m; p = 0.05). Three patients needed to discontinue bosentan therapy because of elevated liver function test results. There were no deaths or hospitalizations, and no significant change in arterial oxygen saturation had occurred at 12 months. Bosentan therapy improved hemodynamics and NYHA class in patients with PAH that was associated with CHD. These effects were seen after 3 to 6 months. Bosentan therapy may provide an effective alternative to current therapies in this patient population.

An Open-Label, Multicentre Pilot Study of Bosentan in Pulmonary Arterial Hypertension Related to Congenital Heart Disease

Bosentan has been shown to be a safe and efficacious treatment for idiopathic pulmonary arterial hypertension (PAH) and PAH associated with connective tissue disease. However, there are limited studies examining the benefits of bosentan in PAH associated with congenital heart disease (CHD). The aim of the present pilot study was to explore the safety and efficacy of bosentan in patients with PAH associated with CHD. In the present study, 11 patients with PAH associated with CHD were enrolled to receive bosentan for a minimum of 16 weeks (62.5 mg twice a day for four weeks; thereafter 125 mg twice a day). Safety was assessed by monitoring adverse events, oxygen saturation, systemic blood pressure, pulse, complete blood count and liver function tests. Efficacy was assessed by the World Health Organization functional class, 6 min walk test (6-MWT), modified Borg dyspnea index, echocardiography and the 36-item short form health survey. Ten patients completed the 16-week treatment period (one patient withdrew). Bosentan was not associated with a deterioration in resting oxygen saturation (83.0+/-4.6% at week 16 versus 81.9+/-6.1% at baseline; P = 0.402), or a deterioration in post-6-MWT oxygen saturation (70.1+/-10.9% at week 16 versus 68.7+/-15.1% at baseline; P = 0.747). Two patients experienced three serious adverse events. The distance walked in 6 min improved significantly by 28 m (P = 0.005) at week 16 compared with baseline, and the modified Borg dyspnea index also improved at week 16 compared with baseline (P = 0.050). The World Health Organization functional class improved from class III to class II for five of 10 patients (50%). Patients' self-rated quality of life (36-item short form health survey) demonstrated a nonsignificant improvement in each of the eight domains. Obtaining reliable echocardiographic measurements was difficult. Most echocardiographic parameters were only measurable on few patients, and none were measured on all patients, questioning the usefulness of echocardiography as a measuring tool for patients with complex CHD. Bosentan was not associated with worsening of resting oxygen saturation or exercise systemic oxygen saturation, suggesting its potential as a safe treatment option for patients with PAH associated with CHD. Improved 6-MWT and the modified Borg dyspnea index also suggested the possibility of bosentan as an efficacious treatment option for these patients. The results of the present study provide evidence for the need and feasibility of a large randomized, placebo-controlled clinical trial.

Bosentan, the mixed ETA–ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion

Endothelin-1 has been shown to be associated with greater myocardial ischemia and reperfusion injury in which oxidative stress plays a key role. The efficacy of bosentan, a mixed ETA-ETB endothelin receptor antagonist, in protecting the myocardium from ischemia-reperfusion injury and oxidative stress was studied in open-chest Wistar rats. Anesthetized adult male rats (175-250 g b wt) underwent sham operation (SHAM group) or were subjected to 40 min of myocardial ischemia (MI) induced by temporary occlusion of the left anterior descending coronary artery (LAD) followed by 2 h reperfusion (R). Rats submitted to the MI-R protocol were administered bosentan at a dose of 3 mg/kg i.v. 20 min (BOS group) or saline (CON group) 20 min post-occlusion of LAD. After the 2 h reperfusion period the animals were euthanized and the heart rapidly excised. Cardiac tissue samples were snap frozen in liquid nitrogen for biochemical assay and were fixed in 10% formalin solution for histologic evaluation. Myocardial I-R resulted in a significant increase (p < 0.05) in the myocardial malondialdehyde levels and a decrease (p < 0.01) in the myocardial reduced glutathione content. These changes were associated with significant decreases in the myocardial activity of antioxidant enzymes superoxide dismutase (p < 0.05) and catalase (p < 0.01) and severe tissue damage in the jeopardized myocardium in the CON group as compared with the non-myocardial ischemia-reperfusion (NMI-R) SHAM group. Bosentan exerted marked tissue protective effect as assessed by histologic evaluation of the myocardium. The drug significantly (p < 0.05) attenuated myocardial oxidative stress and restored the cellular antioxidant defense mechanisms as compared with the saline-treated controls subjected to the MI-R protocol. Furthermore, bosentan also exerted a marked effect on peripheral hemodynamics and heart rate during the reperfusion phase (data reported elsewhere). These results are consistent with the concept that endothelin-1 may be involved in the pathogenesis of myocardial ischemia and infarction. This study demonstrates the antioxidant effect of non-selective endothelin receptor antagonism elucidating that, part of the aetiology of ischemia and reperfusion induced myocardial injury involves impaired antioxidant defenses.

Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: A safe and effective therapy?

Portopulmonary hypertension (PPHTN), a severe complication of portal hypertension is observed in 3%-6% of patients evaluated for liver transplantation. Endothelin-1, a potent vasoconstrictor, is likely to play a role in the pathogenesis of primary pulmonary hypertension, and, in 2 recent trials, the dual endothelin receptor antagonist bosentan has shown beneficial effects in this disease. A role for endothelins in the development of both pulmonary hypertension and cirrhosis has been suggested. We therefore hypothesized that endothelin receptor blockade may be beneficial in the treatment of PPHTN. We report a case of a 42-year-old patient with PPHTN and alcoholic cirrhosis treated with the mixed endothelin receptor antagonist bosentan. The patient rapidly improved from NYHA IV to stage II, experienced a remarkable improvement of 6-minute walking distance from 0 to 590 m within 6 months, and resumed working full-time as a locksmith after 7 months of treatment. Improvement of cardiovascular parameters included a reduction of pulmonary vascular resistance by 60%, a decrease of mean pulmonary artery pressure (mPAP) from 55 to 44 mm Hg at 9 months, and a decline of plasma B-type natriuretic peptide (BNP) from 339 pg/mL to 19 pg/mL after 1 year. There were no adverse events except for a transient decrease in systemic blood pressure. To our knowledge, this is the first report of a patient with PPHTN treated with an endothelin receptor antagonist. The marked and sustained improvement supports the undertaking of controlled studies of the safety and efficacy of bosentan in PPHTN.

The Antagonists of Endothelin Receptors: Results and Perspectives

In 1988 Yanagisawa described endothelins, a new class of vasoconstrictor agents produced by endothelial cells. Further biological effects of these peptides have subsequently been demonstrated, for example, induction of cell proliferation and fibrosis. Two types of endothelin receptors have been described: ET are responsible for endothelininduced vasoconstriction whereas ET induce endothelial cells to release nitric oxide (NO) and prostacyclin. Many antagonists of endothelin receptors have been synthesized and evaluated in animal models and in humans. Satisfactory results have been obtained in animal models of arterial hypertension, pulmonary hypertension, stroke and heart failure but clinical trials have failed to demonstrate that these drugs have a beneficial effect in the treatment of heart failure and a dose-dependent reversible hepatic toxicity has been observed. However, the efficacy of bosentan, a mixed antagonist of endothelin receptors, in the treatment of primary pulmonary hypertension has been demonstrated and the drug is now marketed worldwide for this condition. Further studies are ongoing to evaluate other clinical applications of these drugs. Recently it has been reported that atrasentan, a selective ET antagonist, delayed the progression of hormone-refractory prostate cancer in humans. This review describes the results of the studies performed in animals and in humans and their potential future clinical applications.

Effects of the Endothelin Receptor Antagonist Bosentan on Hemodynamics, Symptoms and Functional Capacity in Japanese Patients With Severe Pulmonary Hypertension

Endothelin (ET)-1 has a pathogenic role in pulmonary arterial hypertension (PAH). Recent clinical studies carried out in Western populations showed that blockade of the ET receptors by bosentan improves pulmonary hemodynamics and exercise capacity. In the present study, the efficacy of bosentan was assessed in Japanese patients with PAH. Because the pharmacokinetics of bosentan and its metabolites are similar in Japanese and Caucasian subjects, the same dose of bosentan, 125 mg twice daily, was administered in the Japanese open-label clinical trial. In 18 patients, mean pulmonary arterial pressure decreased from 52.4+/-13.8 to 46.8+/-13.8 mmHg (p=0.003) and cardiac index increased from 2.20+/-0.74 to 2.61 +/-0.72 L.min(-1).m(-2) (p=0.002). The 6-min walking distance increased from 410+/-89.5 to 494+/-86.0 m (p<0.0001). The dyspnea index (Borg scale) decreased from 3.2+/-2.4 to 2.2+/-1.7 (p=0.02). The specific activity scale (SAS) gradually increased throughout the study period from 2.9+/-0.8 to 4.6+/-1.9 METs (p=0.0005). WHO Class improved in 10 patients. Bosentan was well tolerated and improved the hemodynamics, symptoms, exercise capacity, and quality of life of Japanese patients with PAH. Thus, bosentan can be a valuable therapeutic option in Japanese patients.

Pharmacogenomics in pulmonary arterial hypertension (PAH): the relationship between an ET-1 gene polymorphism (PM) and efficacy of bosentan (BO)

Purpose: ET-1 plays a key role in the pathophysiology of PAH. Levels of ET-1 correlate with the severity of PAH and may be influenced by the presence of certain PMs in the ET-1 gene. BO is an nonselective ET receptor antagonist used to treat PAH. Therefore a pharmacogenetic interaction may occur in patients (pts) with specific ET-1 PMs treated with BO. We investigated whether this interactions exists for the G/T ET-1 PM where the T allele appears to be associated with higher ET-1 levels.

The safety and efficacy of bosentan in pulmonary hypertension due to congenital heart disease

Purpose: Bosentan (B) is an ET receptor antagonist effective in the treatment of some forms pulmonary arterial hypertension (PAH). Few data exist regarding its use in PAH associated with congenital heart disease (PHC). We report our experience in treating PHC with B.