227
Views
2
CrossRef citations to date
0
Altmetric
Review

Recent advances in the management of pulmonary arterial hypertension: lessons from the upfront combination of ambrisentan and tadalafil

, , , , &
Pages 493-504 | Received 29 Jun 2020, Accepted 15 Jan 2021, Published online: 23 Feb 2021

References

  • Galiè N, Humbert M, Vachiery JL, et al. ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016; 37(1): 67–119.
  • Hoeper MM, Humbert M, Souza R, et al. A global view of pulmonary hypertension. Lancet Respir Med. 2016;4(4):306–322.
  • Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1): 1801913.
  • Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2): 376–387.
  • Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9): 1023–1030.
  • Escribano-Subias P, Blanco I, Lopez-Meseguer M, et al. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J. 2012;40(3): 596–603.
  • Hurdman J, Condliffe R, Elliot CA, et al. ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre. Eur Respir J. 2012; 39(4): 945–955.
  • Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019; 53(1): 1801889.
  • Galiè N, Barberá JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015; 373(9): 834–844.
  • Chaisson NF, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. Chest. 2013;144(4):1346–1356.
  • Hassoun PM, Zamanian RT, Damico R, et al. Ambrisentan and tadalafil up-front combination therapy in scleroderma-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2015;192(9):1102–1110.
  • Mercurio V, Mukherjee M, Tedford RJ, et al. Improvement in right ventricular strain with ambrisentan and tadalafil upfront therapy in scleroderma-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2018;197(3):388–391.
  • Coghlan JG, Galiè N, Barberà JA, et al. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann Rheum Dis. 2017;76(7):1219–1227.
  • Klinger JR, Elliott CG, Levine DJ, et al. Therapy for pulmonary arterial hypertension in adults: update of the CHEST guideline and expert panel report. Chest. 2019;155(3):565–586.
  • Sitbon O, Sattler C, Bertoletti L, et al. Initial dual oral combination therapy in pulmonary arterial hypertension. Eur Respir J. 2016;47(6):1727–1736.
  • Chin KM, Sitbon O, Doelberg M, et al. Efficacy and safety of initial triple oral versus initial double oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension (PAH): results of the randomized controlled TRITON Study. Am J Respir Crit Care 2020;201:A2928.
  • Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013; 369(9): 809–818.
  • Ghofrani HA, Galie N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–340.
  • Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015; 373(26): 2522–2533.
  • Torres F, Farber H, Ristic A, et al. Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial. Eur Respir J. 2019;54(4):1901030.
  • D’Alto M, Romeo E, Argiento P, et al. Initial tadalafil and ambrisentan combination therapy in pulmonary arterial hypertension: cLinical and haemodYnamic long-term efficacy (ITALY study). J Cardiovasc Med (Hagerstown). 2018;19(1):12–17.
  • D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343–349.
  • Thenappan T, Shah SJ, Rich S, et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J. 2010;35(5):1079–1087.
  • Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122(2):156–163.
  • Benza RL, Miller DP, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL). Circulation. 2010;122(2):164–172.
  • Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448–456.
  • Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting survival in patients with pulmonary arterial hypertension. Chest. 2019; 156(2): 323–337.
  • Humbert M, Sitbon O, Yaici A, et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010;36(3):549–555.
  • Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. 2012;141(2):354–362.
  • Kylhammar D, Kjellstrom B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018; 39(47): 4175–4181.
  • Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017; 50(2): 1700740.
  • Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Resp J. 2017; 50(2): 1700889.
  • Frost AE, Hoeper MM, Barberá JA, et al. Risk-stratified outcomes with initial combination therapy in pulmonary arterial hypertension: application of the REVEAL risk score. J Heart Lung Transplant. 2018; 37(12): 1410–1417.
  • White RJ, Vonk-Noordegraaf A, Rosenkranz S, et al. Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension. Respir Res. 2019;20(1):208.
  • Kuwana M, Blair C, Takahashi T, et al. Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis. Ann Rheum Dis. 2020;79(5):626–634.
  • Hoeper MM, Apitz C, Grunig E, et al. Targeted therapy of pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol. 2018;272S:37–45.
  • Hoeper MM, Simon RGJ. The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur Respir Rev. 2014;23(134):450–457.
  • McLaughlin VV, Vachiery JL, Oudiz RJ, et al. Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: results from the AMBITION trial. J Heart Lung Transplant. 2019; 38(12): 1286–1295.
  • Rose JA, Cleveland JM, Rao Y, et al. Effect of age on phenotype and outcomes in pulmonary arterial hypertension trials. Chest. 2016;149(5):1234–1244.
  • Hatano S, Strasser T, eds. Primary Pulmonary Hypertension. Report on a WHO Meeting. Geneva: World Health Organization; 1975.
  • Assad TR, Maron BA, Robbins IM, et al. Prognostic effect and longitudinal hemodynamic assessment of borderline pulmonary hypertension. JAMA Cardiol. 2017;2(12):1361–1368.
  • Maron BA, Hess E, Maddox TM, et al. Association of borderline pulmonary hypertension with mortality and hospitalization in a large patient cohort: insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation. 2016; 133(13): 1240–1248.
  • Douschan P, Kovacs G, Avian A, et al. Mild elevation of pulmonary arterial pressure as a predictor of mortality. Am J Respir Crit Care Med. 2018;197(4):509–516.
  • Coghlan JG, Wolf M, Distler O, et al. Incidence of pulmonary hypertension and determining factors in patients with systemic sclerosis. Eur Respir J. 2018;51(4):1701197.
  • Valerio CJ, Schreiber BE, Handler CE, et al. Borderline mean pulmonary artery pressure in patients with systemic sclerosis: transpulmonary gradient predicts risk of developing pulmonary hypertension. Arthritis Rheum. 2013;65(4):1074–1084.
  • Pan Z, Marra AM, Benjamin N, et al. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study). Arthritis Res Ther. 2019;21(1):217.
  • Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347(5):322–329.
  • Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903.
  • Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–2157.
  • Galie N, Olschewski H, Oudiz RJ, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008;117(23):3010–3019.
  • Galie N, Brundage BH, Ghofrani HA, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894–2903.
  • McLaughlin VV, Benza RL, Rubin LJ, et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol. 2010;55(18):1915–1922.
  • Tapson VF, Torres F, Kermeen F, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012;142(6):1383–1390.
  • Tapson VF, Jing ZC, Xu KF, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2013;144(3):952–958.
  • Jing ZC, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013;127(5):624–633.
  • Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296–301.
  • Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165(6):800–804.
  • Gabler NB, French B, Strom BL, et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation. 2012;126(3):349–356.
  • Sitbon O, Gomberg-Maitland M, Granton J, et al., Clinical trial design and new therapies for pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801908. .
  • Avouac J, Kowal-Bielecka O, Pittrow D, et al. Validation of the 6 min walk test according to the OMERACT filter: a systematic literature review by the EPOSS-OMERACT group. Ann Rheum Dis. 2010;69(7):1360–1363.
  • Mercurio V, Bianco A, Campi G, et al. New drugs, therapeutic strategies, and future direction for the treatment of pulmonary arterial hypertension.. Curr Med Chem. 2019;26(16):2844–2864.
  • Committee for Medical Products for Human Use. Guidelines of the clinical investigations of medicinal products for the treatment of pulmonary hypertension 2009. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigations-medicinal-products-treatment-pulmonary-arterial-hypertension_en.pdf [ Last accessed 2nd Apr 2020]
  • ClinicalTrials.gov. Beraprost-314d Added-on to Tyvaso® (BEAT). Available from: https://clinicaltrials.gov/ct2/show/NCT01908699 [ Last accessed 2nd April 2020]
  • ClinicalTrials.gov. Phase III Clinical Worsening Study of UT-15C in subjects with PAH receiving background oral monotherapy (FREEDOM-EV). Available from: https://clinicaltrials.gov/ct2/show/study/NCT01560624 [ Last accessed 2nd April 2020]
  • ClinicalTrials.gov. A study to assess whether macitentan delays disease progression in children with pulmonary arterial hypertension. (PAH) (TOMORROW). Available from: https://clinicaltrials.gov/ct2/show/NCT02932410 [ Last accessed 6th May 2020]
  • McLaughlin VV, Hoeper MM, Channick RN, et al. Pulmonary arterial hypertension-related morbidity is prognostic for mortality. J Am Coll Cardiol. 2018;71(7):752–763.
  • Jimenez D, Quezada CA, Escribano P. Surrogate endpoints for pulmonary hypertension management and trial design: moving in the right direction. J Am Coll Cardiol. 2018;71(7):764–765.
  • Vachiery JL, Galie N, Barbera JA, et al. Initial combination therapy with ambrisentan+tadalafil on pulmonary arterial hypertension related hospitalization in the AMBITION trial. J Heart Lung Transplant. 2019;38(2):194–202.
  • Hoeper MM, McLaughlin VV, Barberá JA, et al. Initial combination therapy with ambrisentan and tadalafil and mortality in patients with pulmonary arterial hypertension: a secondary analysis of the results from the randomised, controlled AMBITION study. Lancet Respir Med. 2016;4(11):894–901.
  • Huber LC, Bye H, Brock M, et al. The pathogenesis of pulmonary hypertension–an update. Swiss Med Wkly. 2015;145:w14202.
  • Guignabert C, Tu L, Le Hiress M, et al. Pathogenesis of pulmonary arterial hypertension: lessons from cancer. Eur Respir Rev. 2013;22(130):543–551.
  • Sitbon O, Canuet M, Picard F, et al. Initial treatment combination with macitentan and tadalafil and tadalafil in patients with pulmonary arterial hypertension: results from the OPTIMA study [Abstract]. Chest. 2019;156(4):A870–A871.
  • Badagliacca R, Papa S, Matsubara H, et al. The importance of right ventricular evaluation in risk assessment and therapeutic strategies: raising the bar in pulmonary arterial hypertension. Int J Cardiol. 2020;301:183–189.
  • Bachetti C, Manes A, Dardi F, et al. Comparison between initial combination therapy and initial monotherapy in pulmonary arterial hypertension: a single centre blinded evaluation of patients enrolled in the AMBITION Study. Am J Respir Crit Care Med. 2015;191:A4779.
  • Kemp K, Savale L, O’Callaghan DS, et al. Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study. J Heart Lung Transplant. 2012;31(2):150–158.
  • Sitbon O, Jais X, Savale L, et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J. 2014;43(6):1691–1697.
  • Galie N, Jansa P, Pulido T, et al. SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension. Eur Heart J. 2017;38(15):1147–1155.
  • Akagi S, Matsubara H, Nakamura K, et al. Modern treatment to reduce pulmonary arterial pressure in pulmonary arterial hypertension. J Cardiol. 2018;72(6):466–472.
  • Badagliacca R, Poscia R, Pezzuto B, et al. Prognostic relevance of right heart reverse remodeling in idiopathic pulmonary arterial hypertension. J Heart Lung Transplant. 2018. 37(2):195–205.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.