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The Patient with Non-Group 2 Pulmonary Hypertension
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Sophia Anastasia Mouratoglou, George Giannakoulas
Bosentan is an endothelin 1 antagonist that blocks both ETA and ETB receptors by binding to them. Bosentan treatment is initiated at a dose of 62.5 mg twice daily for four weeks and then the dose is increased to the approved maintenance dose of 125 mg twice daily. In the BREATH-1 trial, patients in the bosentan arm showed a significant improvement in the 6-minute walk test distance and WHO functional class compared with the placebo arm42 In mildly symptomatic PAH, improvements in pulmonary vascular resistance and delayed time to clinical worsening vs placebo were observed in the EARLY study.43 Bosentan was also evaluated with respect to response of other forms of PAH, such as Eisenmenger syndrome (BREATH-5 study),44,45 in pediatric patients,46 HIV-related PAH,47 and in those with porto-pulmonary hypertension.48 Monitoring of liver transaminases is required in patients treated with bosentan as elevated aspartate aminotransferase or alanine aminotransferase levels more than three times the upper limit of normal subject are not uncommon during therapy and may necessitate dose reduction or treatment discontinuation.
Cardiac diseases in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Saravanan Kuppuswamy, Sudarshan Balla
Bosentan may have teratogenic effects (73) and is, thus, contraindicated during pregnancy; limited data on sildenafil suggest no deleterious effects on the mother or offspring (74). Calcium channel blockers are safe during pregnancy (75) and may prevent preterm labor (76), a common complication in patients with PAH. However, calcium channel blockers may be beneficial only in responders to vasoreactivity tests, and only 6.8% are reported to have a long-term benefit (77).
Termination and Contraceptive Options for the Cardiac Patient
Published in Afshan B. Hameed, Diana S. Wolfe, Cardio-Obstetrics, 2020
Bosentan—a dual endothelin receptor antagonist commonly used in the treatment of pulmonary artery hypertension—interacts with etonogestrel, reducing its efficacy (see section “Pregnancy Contraindicated [WHO Class IV], Pulmonary Artery Hypertension”).
Management of pulmonary arterial hypertension during pregnancy
Published in Expert Review of Respiratory Medicine, 2023
Kaushiga Krishnathasan, Andrew Constantine, Isma Rafiq, Ana Barradas Pires, Hannah Douglas, Laura C Price, Konstantinos Dimopoulos
Interaction with PAH therapies should be kept in mind when selecting the mode of contraception. Interaction of progesterone-based compounds is more apparent with Bosentan, which reduces the efficacy of hormonal agents, including emergency contraception; therefore, women on Bosentan should be on dual contraception [1,3,19]. These recommendations have been extended to all ERAs. Sterilization is a more permanent option but is not routinely used as it often requires general anesthesia, which in PAH carries significant risks. Moreover, it is an invasive procedure and failure is not uncommon. The permanent nature of this procedure may also be unacceptable to some women [49]. Overall, combining two different contraceptive methods, e.g. hormonal plus barrier, is a reasonable option and likely to be the most effective [1,3,50].
The use of pulmonary arterial hypertension therapies in Eisenmenger syndrome
Published in Expert Review of Cardiovascular Therapy, 2021
Alexandra Arvanitaki, Gerhard-Paul Diller
Bosentan, a dual ERA, was the first drug to be studied in a double-blind placebo-controlled randomized clinical trial (RCT) in patients with ES (Bosentan Randomized Trial of Endothelin Agonist Therapy-5/ BREATHE-5 trial) [9]. It was well tolerated and improved exercise capacity [six-minute walking distance (6-MWD) increased by 53.1 m in ES vs. controls] and hemodynamics (decreased mPAP by 5.5 mmHg and PVR index by 472.0 dyne · s · cm−5 in ES vs. controls) without compromising peripheral oxygen saturation in 16 weeks [9]. A post-hoc analysis of BREATHE-5 showed similar improvement in exercise capacity and hemodynamics, without causing desaturation, between ES patients with an atrial septal defect (ASD) and those with a ventricular septal defect (VSD) [10]. Furthermore, sustained long-term exercise capacity and symptom improvement demonstrated in BREATHE-5 24-week, open-label extension study, resulted in bosentan being recommended as a first-class drug in symptomatic patients with ES [11,12]. Numerous observational studies confirmed the beneficial effects of bosentan on functional class, 6-MWD, arterial oxygen saturation at rest and hemodynamics [13]. Most long-term observational studies suggest that clinical benefits of bosentan can be maintained for at least 2 years, without major safety or tolerability issues [13–16]. Initiation dose in most studies was 62.5 mg bid for 4 weeks and up-titration to 125 mg bid thereafter.
Phase three clinical trials in idiopathic pulmonary fibrosis
Published in Expert Opinion on Orphan Drugs, 2021
Giacomo Sgalla, Marialessia Lerede, Luca Richeldi
Bosentan, an ETa and ETb endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension, was tested in 2008 with a phase III randomized, double blind placebo-controlled trial (ClinicalTrials.gov Identifier NCT00071461) called BUILD-1 (Bosentan Use in Interstitial Lung Disease). The administration of an oral daily dose of bosentan for 12 months in mild-moderate IPF patients did not meet the primary outcome of improvement in exercise tolerance (expressed as change from baseline in the 6-minute walking distance). On the other hand, Bosentan showed positive results with regards to a few secondary endpoints, including time to death or disease progression and dyspnea scores in a subgroup of randomized subjects with histological IPF diagnosis [37,[38]. Nevertheless, a second phase III trial with the same design (BUILD-3, ClinicalTrials.gov Identifier NCT00391443) published in 2011 did not show any efficacy of Bosentan in reducing morbidity and mortality in IPF patients [39].