Figures & data
Table 1. Currently available studies assessing disease targeting therapies in pulmonary arterial hypertension associated with congenital heart disease and selected studies of mixed pulmonary arterial hypertension populations.
Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 99(14), 1858–1865 (1999). Olschewski H, Simonneau G, Galiè N et al.; Aerosolized Iloprost Randomized Study Group. Inhaled iloprost for severe pulmonary hypertension. N. Engl. J. Med. 347(5), 322–329 (2002). Rubin LJ, Badesch DB, Barst RJ et al. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. 346(12), 896–903 (2002). 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 doubleblind, randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 165(6), 800–804 (2002). Fernandes SM, Newburger JW, Lang P et al. Usefulness of epoprostenol therapy in the severely ill adolescent/adult with Eisenmenger physiology. Am. J. Cardiol. 91(5), 632–635 (2003). Christensen DD, McConnell ME, Book WM, Mahle WT. Initial experience with bosentan therapy in patients with the Eisenmenger syndrome. Am. J. Cardiol. 94(2), 261–263 (2004). Barst RJ, Langleben D, Frost A et al.; STRIDE-1 Study Group. Sitaxsentan therapy for pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 169(4), 441–447 (2004). Schulze-Neick I, Gilbert N, Ewert R et al. Adult patients with congenital heart disease and pulmonary arterial hypertension: first open prospective multicenter study of bosentan therapy. Am. Heart J. 150(4), 716 (2005). Gatzoulis MA, Rogers P, Li W et al. Safety and tolerability of bosentan in adults with Eisenmenger physiology. Int. J. Cardiol. 98(1), 147–151 (2005). 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. 353(20), 2148–2157 (2005). 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 114(1), 48–54 (2006). Kotlyar E, Sy R, Keogh AM et al. Bosentan for the treatment of pulmonary arterial hypertension associated with congenital cardiac disease. Cardiol. Young 16(3), 268–274 (2006). Benza RL, Rayburn BK, Tallaj JA et al. Efficacy of bosentan in a small cohort of adult patients with pulmonary arterial hypertension related to congenital heart disease. Chest 129(4), 1009–1015 (2006). Sitbon O, Beghetti M, Petit J et al. Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects. Eur. J. Clin. Invest. 36(Suppl. 3), 25–31 (2006). Mukhopadhyay S, Sharma M, Ramakrishnan S et al. Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study. Circulation 114(17), 1807–1810 (2006). Singh TP, Rohit M, Grover A, Malhotra S, Vijayvergiya R. A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension. Am. Heart J. 151(4), 851.e1–851.e5 (2006). Barst RJ, Langleben D, Badesch D et al.; STRIDE-2 Study Group. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J. Am. Coll. Cardiol. 47(10), 2049–2056 (2006). D’Alto M, Vizza CD, Romeo E et al. Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect. Heart 93(5), 621–625 (2007). Apostolopoulou SC, Manginas A, Cokkinos DV, Rammos S. Long-term oral bosentan treatment in patients with pulmonary arterial hypertension related to congenital heart disease: a 2-year study. Heart 93(3), 350–354 (2007). Diller GP, Dimopoulos K, Kaya MG et al. Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease. Heart 93(8), 974–976 (2007). van Loon RL, Hoendermis ES, Duffels MG et al. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: does the beneficial effect persist? Am. Heart J. 154(4), 776–782 (2007). Chau EM, Fan KY, Chow WH. Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension. Int. J. Cardiol. 120(3), 301–305 (2007). Gatzoulis MA, Beghetti M, Galiè N et al.; BREATHE-5 Investigators. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study. Int. J. Cardiol. 127(1), 27–32 (2008). 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 117(23), 3010–3019 (2008). 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 119(22), 2894–2903 (2009). Duffels MG, Vis JC, van Loon RL et al. Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down’s syndrome. Am. J. Cardiol. 103(9), 1309–1315 (2009). Dimopoulos K, Inuzuka R, Goletto S et al. Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Circulation 121(1), 20–25 (2010). Kermeen FD, Franks C, O’Brien K et al. Endothelin receptor antagonists are an effective long term treatment option in pulmonary arterial hypertension associated with congenital heart disease with or without trisomy 21. Heart. Lung Circ. 19(10), 595–600 (2010). Lu XL, Xiong CM, Shan GL et al. Impact of sildenafil therapy on pulmonary arterial hypertension in adults with congenital heart disease. Cardiovasc. Ther. 28(6), 350–355 (2010). Vis JC, Duffels MG, Mulder P et al. Prolonged beneficial effect of bosentan treatment and 4-year survival rates in adult patients with pulmonary arterial hypertension associated with congenital heart disease. Int. J. Cardiol. 164(1), 64–69 (2013). D’Alto M, Romeo E, Argiento P et al. Therapy for pulmonary arterial hypertension due to congenital heart disease and Down’s syndrome. Int. J. Cardiol. 164(3), 323–326 (2013). Zeng WJ, Lu XL, Xiong CM et al.; Sildenafil Therapy on Pulmonary Arterial Hypertension Associated With Different Types of Congenital Heart Disease Study Group. The efficacy and safety of sildenafil in patients with pulmonary arterial hypertension associated with the different types of congenital heart disease. Clin. Cardiol. 34(8), 513–518 (2011). Monfredi O, Griffiths L, Clarke B, Mahadevan VS. Efficacy and safety of bosentan for pulmonary arterial hypertension in adults with congenital heart disease. Am. J. Cardiol. 108(10), 1483–1488 (2011). D’Alto M, Romeo E, Argiento P et al. Bosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology. Int. J. Cardiol. 155(3), 378–382 (2012). Dong MF, Ma ZS, Ma SJ et al. Effect of prostaglandin E1 on pulmonary arterial hypertension following corrective surgery for congenital heart disease. J. Cardiovasc. Pharmacol. Ther. 17(3), 303–307 (2012). Diller GP, Alonso-Gonzalez R, Dimopoulos K et al. Disease targeting therapies in patients with Eisenmenger syndrome: response to treatment and long-term efficiency. Int. J. Cardiol. doi:10.1016/j.ijcard.2012.02.007 (2012) (Epub ahead of print).