Update on pulmonary arterial hypertension pharmacotherapy

References

• Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S55–S66.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Galiè N, Manes A, Negro L, et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394–403.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109:159–165.
   PubMed Web of Science ®Google Scholar
• Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 2012;122(12):4306–4313.
   PubMed Web of Science ®Google Scholar
• Sutendra G, Michelakis ED. The metabolic basis of pulmonary arterial hypertension. Cell Metab. 2014;19(4):558–573.
   PubMed Web of Science ®Google Scholar
• Alves JL Jr, Gavilanes F, Jardim C, et al. Pulmonary arterial hypertension in the southern hemisphere: results from registry of incident Brazilian cases. Chest. 2015;147(2):495–501.
   PubMed Web of Science ®Google Scholar
• Jing ZC, Xu XQ, Han ZY, et al. Registry and survival study in Chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest. 2007;132(2):373–379.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Huscher D, Ghofrani HA, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2013;168(2):871–880.
   PubMed Web of Science ®Google Scholar
• Frost AE, Farber HW, Barst RJ, et al. Demographics and outcomes of patients diagnosed with pulmonary hypertension with pulmonary capillary wedge pressures 16 to 18 mm Hg: insights from the REVEAL registry. Chest. 2013;143(1):185–195.
   PubMed Web of Science ®Google Scholar
• McLaughlin VV, Archer SL, Badesch DB, et al. American college of cardiology foundation task force on expert consensus documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573–1619.
   PubMed Web of Science ®Google Scholar
• Galiè N, Barberà JA, Frost AE, et al. AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373(9):834–844.
   PubMed Web of Science ®Google Scholar
• Provencher S, Granton JT. Current treatment approaches to pulmonary arterial hypertension. Can J Cardiol. 2015;31(4):460–477.
   PubMed Web of Science ®Google Scholar
• Sandoval J, Aguirre JS, Pulido T, et al. Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am J Respir Crit Care Med. 2001;164:1682–1687.
   PubMed Web of Science ®Google Scholar
• Cohn JN. Optimal diuretic therapy for heart failure. Am J Med. 2001;111:577.
   PubMed Web of Science ®Google Scholar
• Rhodes CJ, Howard LS, Busbridge M, et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol. 2011;58:300–309.
   PubMed Web of Science ®Google Scholar
• Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation. 1987;76(1):135–141.
   PubMed Web of Science ®Google Scholar
• Galiè N, Torbicki A, Barst R, et al. Task force. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The taskforce on diagnosis and treatment of pulmonary arterial hypertension of the European society of cardiology. Eur Heart J. 2004;25(24):2243–2278.
   PubMed Web of Science ®Google Scholar
• Sitbon O, Humbert M, Jaïs X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111:3105–3111.
   PubMed Web of Science ®Google Scholar
• Galiè N, Ghofrani HA, Torbicki A, et al. Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) study group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–2157.
   PubMed Web of Science ®Google Scholar
• Rubin LJ, Badesch DB, Fleming TR, et al. SUPER-2 study group. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study. Chest. 2011;140(5):1274–1283.
   PubMed Web of Science ®Google Scholar
• Galiè N, Brundage BH, Ghofrani HA, et al. Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) study group. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894–2903.
   PubMed Web of Science ®Google Scholar
• Oudiz RJ, Brundage BH, Galiè N, et al. PHIRST study group. Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study. J Am Coll Cardiol. 2012;60(8):768–774.
   PubMed Web of Science ®Google Scholar
• Jing ZC, Yu ZX, Shen JY, et al. Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension (EVALUATION) study group vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2011;183(12):1723–1729.
   PubMed Web of Science ®Google Scholar
• Ghofrani HA, Galiè N, Grimminger F, et al. PATENT-1 study group. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–340.
   PubMed Web of Science ®Google Scholar
• Galiè N, Müller K, Scalise AV, et al. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur Respir J. 2015;45(5):1314–1322.
   PubMed Web of Science ®Google Scholar
• Long term extention study in patients with pulmonary arteril hypertension (PATENT-2). [Cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/show/NCT00863681
   Google Scholar
• Vane J, Corin RE. Prostacyclin: a vascular mediator. Eur J Vasc Endovasc Surg. 2003;26(6):571–578.
   PubMed Web of Science ®Google Scholar
• Wharton J, Davie N, Upton PD, et al. Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells. Circulation. 2000;102(25):3130–3136.
   PubMed Web of Science ®Google Scholar
• Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med. 1990;112(7):485–491.
   PubMed Web of Science ®Google Scholar
• Barst RJ, Rubin LJ, Long WA, et al. Primary pulmonary hypertension study group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296–301.
   PubMed Web of Science ®Google Scholar
• Galiè N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60–D72.
   PubMed Web of Science ®Google Scholar
• Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J. 2008;31(4):891–901.
   PubMed Web of Science ®Google Scholar
• Chin KM, Badesch DB, Robbins IM, et al. Two formulations of epoprostenol sodium in the treatment of pulmonary arterial hypertension: EPITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), a phase IV, open-label, randomized study. Am Heart J. 2014;167(2):218–225.
   PubMed Web of Science ®Google Scholar
• Simonneau G, Barst RJ, Galie N, et al. Treprostinil study group. 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.
   PubMed Web of Science ®Google Scholar
• Benza RL, Seeger W, McLaughlin VV, et al. Long-term effects of inhaled treprostinil in patients with pulmonary arterial hypertension: the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study open-label extension. J Heart Lung Transplant. 2011;30(12):1327–1333.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Olschewski H, Simonneau G, Galiè N, et al. Aerosolized iloprost randomized study group. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347(5):322–329.
   PubMed Web of Science ®Google Scholar
• Opitz CF, Wensel R, Winkler J, et al. Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. Eur Heart J. 2005;26(18):1895–1902.
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Gall H, Seyfarth HJ, et al. Long-term outcome with intravenous iloprost in pulmonary arterial hypertension. Eur Respir J. 2009;34(1):132–137.
   PubMed Web of Science ®Google Scholar
• Galiè N, Humbert M, Vachiéry JL, et al. Arterial Pulmonary Hypertension and Beraprost European (ALPHABET) study group. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2002;39(9):1496–1502.
   PubMed Web of Science ®Google Scholar
• Barst RJ, McGoon M, McLaughlin V, et al. Beraprost study group. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2003;41(12):2119–2125.
   PubMed Web of Science ®Google Scholar
• Sitbon O, Channick R, Chin KM, et al. GRIPHON investigators. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373(26):2522–2533.
   PubMed Web of Science ®Google Scholar
• 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(24):1732–1739.
   PubMed Web of Science ®Google Scholar
• Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903.
   PubMed Web of Science ®Google Scholar
• McLaughlin VV, Sitbon O, Badesch DB, et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J. 2005;25(2):244–249.
   PubMed Web of Science ®Google Scholar
• Galiè N, Rubin L, Hoeper M, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371(9630):2093–2100.
   PubMed Web of Science ®Google Scholar
• Galiè N, Beghetti M, Gatzoulis MA, et al. Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) Investigators. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114(1):48–54.
   PubMed Web of Science ®Google Scholar
• Humbert M, Segal ES, Kiely DG, et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J. 2007;30(2):338–344.
   PubMed Web of Science ®Google Scholar
• Galiè N, Olschewski H, Oudiz RJ, et al. Ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy studies (ARIES) group. 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.
   PubMed Web of Science ®Google Scholar
• Oudiz RJ, Galiè N, Olschewski H. ARIES study group. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(21):1971–1981.
   PubMed Web of Science ®Google Scholar
• Badesch DB, Feldman J, Keogh A, et al. ARIES-3 study group. ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension. Cardiovasc Ther. 2012;30(2):93–99.
   PubMed Web of Science ®Google Scholar
• McGoon MD, Frost AE, Oudiz RJ, et al. Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities. Chest. 2009;135(1):122–129.
   PubMed Web of Science ®Google Scholar
• Pulido T, Adzerikho I, Channick RN, et al. SERAPHIN investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–818.
   PubMed Web of Science ®Google Scholar
• Channick RN, Delcroix M, Ghofrani HA, et al. Effect of macitentan on hospitalizations: results from the SERAPHIN trial. JACC Heart Fail. 2015;3(1):1–8.
   PubMed Web of Science ®Google Scholar
• Sidharta PN, Treiber A, Dingemanse J. Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonistmacitentan. Clin Pharmacokinet. 2015;54(5):457–471.
   PubMed Web of Science ®Google Scholar
• Hurst N, Pellek M, Dingemanse J, et al. Lack of pharmacokinetic interactions between macitentan and a combined oral contraceptive in healthy female subjects. J Clin Pharmacol. 2015. Epub Sep 18. doi:10.1002/jcph.639.
   PubMedGoogle Scholar
• McLaughlin V, Channick RN, Ghofrani HA, et al. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. 2015;46(2):405–413.
   PubMed Web of Science ®Google Scholar
• Galiè N, Palazzini M, Manes A. Pulmonary arterial hypertension: from the kingdom of the near-dead to multipleclinical trial meta-analyses. Eur Heart J. 2010;31(17):2080–2086.
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Markevych I, Spiekerkoetter E, et al. Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J. 2005;26(5):858–863.
   PubMed Web of Science ®Google Scholar
• Fox BD, Shimony A, Langleben D. Meta-analysis of monotherapy versus combination therapy for pulmonary arterial hypertension. Am J Cardiol. 2011;108(8):1177–1182.
   PubMed Web of Science ®Google Scholar
• Johnson SR, Brode SK, Mielniczuk LM, et al. Dual therapy in IPAH and SSc-PAH. A qualitative systematic review. Respir Med. 2012;106(5):730–739.
   PubMed Web of Science ®Google Scholar
• Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46(4):903–975.
   PubMed Web of Science ®Google Scholar
• Simonneau G, Rubin LJ, Galiè N, et al. PACES study group. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. 2008;149(8):521–530.
   PubMed Web of Science ®Google Scholar
• Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004;24(3):353–359.
   PubMed Web of Science ®Google Scholar
• McLaughlin VV, Oudiz RJ, 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(11):1257–1263.
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Leuchte H, Halank M, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2006;28(4):691–694.
   PubMed Web of Science ®Google Scholar
• Paulin R, Michelakis ED. The metabolic theory of pulmonary arterial hypertension. Circ Res. 2014;115(1):148–164.
   PubMed Web of Science ®Google Scholar
• McMurtry MS, Bonnet S, Wu X, et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res. 2004;95(8):830–840.
   PubMed Web of Science ®Google Scholar
• Sutendra G, Michelakis ED. The metabolic basis of pulmonary arterial hypertension. Cell Metab. 2014;19(4):558–573.
   PubMed Web of Science ®Google Scholar
• Dromparis P, Michelakis ED. Mitochondria in vascular health and disease. Annu Rev Physiol. 2013;75:95–126.
   PubMed Web of Science ®Google Scholar
• Dromparis P, Sutendra G, Michelakis ED. The role of mitochondria in pulmonary vascular remodeling. J Mol Med (Berl). 2010;88(10):1003–1010.
   PubMed Web of Science ®Google Scholar
• Bonnet S, Michelakis ED, Porter CJ, et al. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation. 2006;113(22):2630–2641.
   PubMed Web of Science ®Google Scholar
• Piao L, Sidhu VK, Fang YH, et al. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate. J Mol Med (Berl). 2013;91(3):333–346.
   PubMed Web of Science ®Google Scholar
• Dichloroacetate (DCA) for the treatment of pulmonary arterial hypertension. [Cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT01083524?term=Dichloroacetate+pulmonary+hypertension&rank=1.
   Google Scholar
• Sutendra G, Bonnet S, Rochefort G, et al. Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension. Sci Transl Med. 2010;2(44):44–58.
   Google Scholar
• Hawwa N, Menon V. Ranolazine: clinical applications and therapeutic basis. Am J Cardiovasc Drugs. 2013;13(1):5–16.
   PubMed Web of Science ®Google Scholar
• A study of ranolazine acute aministration and short term administration in pulmonar hypertwnsion. [Cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show?term=ranolazine+PAH&rank=1
   Google Scholar
• Khan SS, Cuttica MJ, Beussink-Nelson L, et al. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study. Pulm Circ. 2015;5(3):547–556.
   PubMed Web of Science ®Google Scholar
• Targeting the right ventricle in pulmonary hypertension. [Cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT01839110?term=NCT01839110&rank=1
   Google Scholar
• Trimetazidine in pulmonary artery hypertension. [Cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT02102672?term=Trimetazidine+PAH&rank=1
   Google Scholar
• Duong-Quy S, Bei Y, Liu Z, et al. Role of Rho-kinase and its inhibitors in pulmonary hypertension. Pharmacol Ther. 2013;137(3):352–364.
   PubMed Web of Science ®Google Scholar
• Guilluy C, Eddahibi S, Agard C, et al. RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling. Am J Respir Crit Care Med. 2009;179(12):1151–1158.
   PubMed Web of Science ®Google Scholar
• Abe K, Shimokawa H, Morikawa K, et al. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res. 2004;94(3):385–393.
   PubMed Web of Science ®Google Scholar
• Li F, Xia W, Li A, et al. Long-term inhibition of Rho kinase with fasudil attenuates high flow induced pulmonary artery remodeling in rats. Pharmacol Res. 2007;55(1):64–71.
   PubMed Web of Science ®Google Scholar
• Liu AJ, Ling F, Wang D, et al. Fasudil inhibits platelet-derived growth factor-induced human pulmonary arterysmooth muscle cell proliferation by up-regulation of p27kip via the ERK signalpathway. Chin Med J (Engl). 2011;124(19):3098–3104.
   PubMed Web of Science ®Google Scholar
• Fukumoto Y, Matoba T, Ito A, et al. Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart. 2005;91(3):391–392.
   PubMed Web of Science ®Google Scholar
• Fujita H, Fukumoto Y, Saji K, et al. Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension. Heart Vessels. 2010;25(2):144–149.
   PubMed Web of Science ®Google Scholar
• Fukumoto Y, Yamada N, Matsubara H, et al. Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor inpulmonary arterial hypertension. Circ J. 2013;77(10):2619–2625.
   PubMed Web of Science ®Google Scholar
• Pankey EA, Byun RJ, Smith WB, et al. The Rho kinase inhibitor azaindole-1 has long-acting vasodilator activity in the pulmonary vascular bed of the intact chest rat. Can J Physiol Pharmacol. 2012;90(7):825–835.
   PubMed Web of Science ®Google Scholar
• Bonnet S, Rochefort G, Sutendra G, et al. The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci USA. 2007;104(27):11418–11423.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Li M, Zhang Y, et al. The effects and mechanisms of mycophenolate mofetil on pulmonary arterial hypertension in rats. Rheumatol Int. 2010;30(3):341–348.
   PubMed Web of Science ®Google Scholar
• Campos M, Schiopu E. Pulmonary arterial hypertension in adult-onset still’s disease: Rapid response to anakinra. Case Rep Rheumatol. 2012;2012:537–613.
   Google Scholar
• Jones JE, Walker JL, Song Y, et al. Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol. 2004;286(5):H1775–H1784.
   Google Scholar
• Tian W, Jiang X, Tamosiuniene R. locking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Sci Transl Med. 2013;5(200):200ra117.
   PubMed Web of Science ®Google Scholar
• Schermuly RT, Dony E, Ghofrani HA, et al. Reversal of experimental pulmonary hypertension by PDGFinhibition. J Clin Invest. 2005;115(10):2811–2821.
   PubMed Web of Science ®Google Scholar
• Ghofrani HA, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med. 2005;353(13):1412–1413.
   PubMed Web of Science ®Google Scholar
• Souza R, Sitbon O, Parent F, et al. long term imatinib treatment in pulmonary arterial hypertension. Thorax. 2006;61(8):736.
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Barst RJ, Bourge RC, et al. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013;127(10):1128–1138.
   PubMed Web of Science ®Google Scholar
• Shah AM, Campbell P, Rocha GQ, et al. IMPRES investigators. Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension. Eur Heart J. 2015;36(10):623–632.
   PubMed Web of Science ®Google Scholar
• Extension to QTI571A2301 to evaluate the long-term safety, tolerability and efficacy of imatinib in severe pulmonary hypertension. [Cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show?term=imatinib+PAH&rank=3
   Google Scholar