- |||||||||| Tracleer (bosentan) / J&J, Roche
Journal: High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET/ET Receptor and mTOR Pathway. (Pubmed Central) - Nov 27, 2022
However, the inhibition of either ET-R alone by ambrisentan or ET-R/ET-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. Altogether, our findings prove that ET-1 signaling under HG conditions leads to a significant mitochondrial dysfunction involving contributions from the mTOR pathway.
- |||||||||| Uptravi (selexipag) / J&J, Nippon Shinyaku, Opsumit (macitentan) / Nippon Shinyaku, J&J
Journal: Pharmacological counseling in hepatotoxicity induced by macitentan and selexipag: a case report. (Pubmed Central) - Oct 26, 2022
It is possible to become an alternative for rapid analysis of drug-protein interaction. A multidisciplinary approach based on clinical evaluation, as well as pharmacological counseling and evaluation of the patient's genetic profile, might be useful for identification of patients with a high chance of drug-induced liver injury, avoiding unnecessary risks in therapy selection and prescription.
- |||||||||| ambrisentan / Generic mfg.
Enrollment change, Trial completion date, Trial primary completion date: A Study of Micro Dose Ambrisentan in Hospitalized Patients With Respiratory Insufficiency Due to COVID-19 (clinicaltrials.gov) - Oct 20, 2022
P2, N=232, Recruiting,
A multidisciplinary approach based on clinical evaluation, as well as pharmacological counseling and evaluation of the patient's genetic profile, might be useful for identification of patients with a high chance of drug-induced liver injury, avoiding unnecessary risks in therapy selection and prescription. N=150 --> 232 | Trial completion date: Oct 2022 --> Jul 2023 | Trial primary completion date: Jul 2022 --> Apr 2023
- |||||||||| ambrisentan / Generic mfg., sildenafil / Generic mfg., eplerenone / Generic mfg.
A RARE CASE OF BILATERAL RETINAL DETACHMENT AS A SEQUELA OF PULMONARY ARTERIAL HYPERTENSION (Convention Center Exhibit Hall: Poster Area) - Sep 11, 2022 - Abstract #CHEST2022CHEST_3134;
On conclusion of the study, the patient was transitioned to epoprostenol/sildenafil/ambrisentan triple therapy and referred for double lung transplantation...She was subsequently started on eplerenone by ophthalmology with some improvement in her vision... Retinal detachment remains a rare complication of pulmonary arterial hypertension, with life-altering consequences if left untreated.
- |||||||||| Review, Journal: Drug-Drug Interactions in the Management of Patients with Pulmonary Arterial Hypertension. (Pubmed Central) - Jul 17, 2022
While the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.
- |||||||||| ambrisentan / Generic mfg., sildenafil / Generic mfg., milrinone / Generic mfg.
Mitraclip placement in an adult with single ventricle, systemic-pulmonary fistula and severe single atrioventricular valve insufficiency (Poster eBoard 2) - Jun 17, 2022 - Abstract #Euroanaesthesia2022Euroanaesthesia_1339;
Later, she developed severe postcapillary pulmonary hypertension and despite medical treatment with sildenafil and ambrisentan she suffered a decompensated heart failure secondary to severe single atrioventricular valve insufficiency...Milrinone and an extracorporeal membrane oxygenation device were available in the operating room...It is well established which drugs are appropriate for each goal. However, there is controversy in the use of vasopressin instead of α-drugs as systemic vasopressor2.
- |||||||||| Adempas (riociguat) / Bayer, Tracleer (bosentan) / J&J, Roche
Review, Journal: Diagnosis and Treatment of Pulmonary Arterial Hypertension: A Review. (Pubmed Central) - Apr 19, 2022
Pulmonary arterial hypertension affects an estimated 10.6 per 1 million adults in the US and, without treatment, typically progresses to right heart failure and death. First-line therapy with drug combinations that target multiple biological pathways are associated with improved survival.
- |||||||||| ambrisentan / Generic mfg.
Trial completion date, Trial primary completion date: Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529 (clinicaltrials.gov) - Apr 8, 2022
P2, N=66, Active, not recruiting,
First-line therapy with drug combinations that target multiple biological pathways are associated with improved survival. Trial completion date: Jan 2022 --> Jun 2022 | Trial primary completion date: Jan 2022 --> Jun 2022
- |||||||||| sildenafil / Generic mfg.
CENTRAL CANNULATION OF VA ECMO FOR SEVERE PULMONARY HYPERTENSION AND CARDIOGENIC SHOCK ([VIRTUAL]) - Mar 23, 2022 - Abstract #SCCM2022SCCM_2568;
Atrial septostomy is also invasive and has shown poor outcomes in patients with end-stage PAH and low CI. In the correct setting, central VA-ECMO could be used in end-stage PAH patients to allow for early remodeling, rather than waiting for this process to occur after transplant.
- |||||||||| VentaProst (epoprostenol inhalation) / Aerogen Pharma
MAJOR NONCARDIAC SURGERY IN A PATIENT WITH SEVERE PULMONARY HYPERTENSION: PERIOPERATIVE CHALLENGES ([VIRTUAL]) - Mar 23, 2022 - Abstract #SCCM2022SCCM_1289;
She was started on tadalafil and ambrisentan with improvement in her functional capacity...Inhaled epoprostenol, infusions of epinephrine and vasopressin were initiated and titrated to maintain stable hemodynamics...Stress and pain from surgical trauma, fluid shifts and ventilation can further exacerbate pulmonary hypertension and cause right-sided heart failure. Selective inhaled pulmonary vasodilators and continued controlled mechanical ventilation, early initiation of enteral pulmonary vasodilators, adequate analgesia and invasive hemodynamic monitoring during the postoperative phase in the ICU are all critically important for a successful perioperative outcome.
- |||||||||| Tracleer (bosentan) / J&J, Roche
Retrospective data, Review, Journal: Comparative assessment of efficacy and safety of ambrisentan and bosentan in patients with pulmonary arterial hypertension: A meta-analysis. (Pubmed Central) - Mar 5, 2022
Selective inhaled pulmonary vasodilators and continued controlled mechanical ventilation, early initiation of enteral pulmonary vasodilators, adequate analgesia and invasive hemodynamic monitoring during the postoperative phase in the ICU are all critically important for a successful perioperative outcome. The results of this network meta-analysis suggest that ambrisentan was similar to bosentan in efficacy, while it exhibited better tolerability with respect to abnormal liver function in comparison with bosentan, in patients with PAH.
- |||||||||| ambrisentan / Generic mfg., tadalafil / Generic mfg.
Cardiac Effort Provides a Reproducible Remote Assessment of 6-Minute Walk Test (Room 303-304 (South Building, Level 3), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_5348;
Remote 6MWT was feasible, appeared safe, and 6MWT distance was shorter than clinic distance. CE calculated by ECG HR and accelerometer-estimated distance provides a reproducible remote assessment of exercise tolerance, comparable to the clinic measured value.
- |||||||||| Nontraumatic Subdural Hematoma: A Cautionary Tale of Anticoagulation with Parenteral Prostacyclin Therapy (Area K, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_4758;
Head imaging should be obtained in the setting of headache when prostacyclin therapy and anticoagulation are being used in combination, especially at low doses. Until further studies support anticoagulation use, caution should be given when using empiric anticoagulation in the management of PAH.
- |||||||||| ambrisentan / Generic mfg., sildenafil / Generic mfg.
Coincidence or Causative: Unique Imaging in a Patient with Pulmonary Arterial Hypertension Due to Congenital Heart Disease (Area K, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_4749;
DiscussionFindings of a congenital branch pulmonary artery can closely resemble CTEPH, and it is important to differentiate the two so that anticoagulation is not inappropriately prescribed. Every CHD-PAH patient is unique and an individualized assessment is necessary when considering vasodilator therapy in this challenging disease state.
- |||||||||| ambrisentan / Generic mfg., furosemide / Generic mfg., lisinopril / Generic mfg.
Permissive Systemic Hypertension in the Management of Eisenmenger Syndrome in a Patient with Patent Ductus Arteriosus (Area K, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_4748;
She was initiated on ambrisentan and treprostinil with significant symptom improvement...On follow-up, lisinopril was started for stage 2 hypertension but stopped for return of dyspnea and worsening hypoxia...Her hypoxia correlated with systolic blood pressures less than 140mmHg and so she has remained off all anti-hypertensives aside from furosemide...If left uncorrected, patients can develop irreversible PH, shunt flow reversal, and cyanosis, a syndrome known as ES. This case illustrates a unique scenario in which permissive systemic hypertension is essential in minimizing right-to-left shunting in a patient with ES who is already on maximum medical therapy.
- |||||||||| ambrisentan / Generic mfg., sildenafil / Generic mfg.
Reverse Bernheim Phenomenon - Always a Conundrum (Area K, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_4742;
Circulation. 1950;1:759-765.
- |||||||||| Adempas (riociguat) / Bayer, Merck (MSD), Uptravi (selexipag) / J&J, Nippon Shinyaku
Pulmonary Hypertension Associated with Systemic Scleroderma in a Pediatric Patient (Area B, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_4679;
This case highlights the importance of maintaining suspicion for CTD in the pediatric PAH population, as PAH may be the presenting symptom for CTD-PAH. This case also demonstrates the possibility of successful pediatric CTD-PAH control with PAH therapy and immune modulation.
- |||||||||| ambrisentan / Generic mfg., sildenafil / Generic mfg.
Atypical Alveolar Capillary Dysplasia in a 13-Year-Old Mistaken for Bronchopulmonary Dysplasia (Area E, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_1326;
He was diagnosed with BPD-associated PH and treated with supplemental oxygen and sildenafil...Ambrisentan was added at 7-years-old for recurrent exercise intolerance and continued evidence of PH...Increased genetic testing in children with PH has revealed notable phenotypic variance in atypical ACD/MPV, which may involve genetic mosaicism, parental imprinting, and heterogenous disease allowing for compensatory growth of normal areas of lung. In children with persistent PH, chronic lung disease, and GI and/or cardiac anomalies, ACD/MPV should be considered.
- |||||||||| ambrisentan / Generic mfg.
Journal, Combination therapy: Positive Predictors for Response to Ambrisentan Combination Therapy in Pulmonary Arterial Hypertension. (Pubmed Central) - Feb 8, 2022
P3
At multivariate analysis, female sex (odds ratio [OR] 2.67; 95% confidence interval [CI] 1.29, 5.52; P = 0.0081), longer 6-minute walk distance (OR 1.01; 95% CI 1.00, 1.01; P = 0.0039), lower baseline log N-terminal-prohormone of brain natriuretic peptide (OR 0.70; 95% CI 0.52, 0.94; P = 0.0190), and aldosterone antagonist use (OR 2.54; 95% CI 1.03, 6.26; P = 0.0436) independently predicted response to initial combination therapy.Besides demographic factors, the absence of comorbidities and less severe disease state, and the use of aldosterone antagonist therapy identified patients with PAH most likely to respond to initial combination therapy with ambrisentan and tadalafil. Further study to evaluate the role of aldosterone antagonist therapy in PAH is warranted.
- |||||||||| ambrisentan / Generic mfg., tadalafil / Generic mfg.
Journal, Combination therapy: Combination Therapy in Pulmonary Arterial Hypertension-Targeting the Nitric Oxide and Prostacyclin Pathways. (Pubmed Central) - Jan 29, 2022
Although there is a paucity of prospective data, preclinical data and results from secondary data analysis of clinical studies targeting these pathways may provide novel insights into this alternative combination as a reasonable, and sometimes preferred, alternative approach to combination therapy in PAH. This review of preclinical and clinical data will discuss the current understanding of combination therapy that simultaneously targets the NO and PGI signaling pathways, highlighting the clinical advantages and theoretical biochemical interplay of these agents.
- |||||||||| ambrisentan / Generic mfg.
Journal: Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK. (Pubmed Central) - Jan 27, 2022
As prognostic factors, high EDNRA/ILK expression correlates with poor SOC clinical outcome. These findings provide a framework for the ET-1R/β-arr1 pathway as an integrator of ILK/Rac3-dependent adhesive and proteolytic signaling to invadopodia, favoring cancer/stroma interactions and metastatic behavior.
- |||||||||| Opsumit (macitentan) / Nippon Shinyaku, J&J
Journal: The Endothelin Receptor Antagonist Macitentan Inhibits Human Cytomegalovirus Infection. (Pubmed Central) - Dec 25, 2021
Ganciclovir and its pro-drug valganciclovir are the preferred drugs in use today for prophylaxis and treatment of viremic patients...We infected these cells with HCMV and treated them with the ETBR specific antagonist BQ788 or ETR antagonists that are approved by the FDA for treatment of pulmonary hypertension; macitentan, its metabolite ACT-132577, bosentan and ambrisentan, and as an anti-viral control, we used ganciclovir or letermovir...Of importance, macitentan also inhibited productive infection of a ganciclovir-resistant HCMV isolate. Our results suggest that binding or signaling through ETBR is crucial for viral replication, and that selected ETBR blockers inhibit HCMV infection.
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