Pharmaceutical Therapies for Chronic Obstructive Pulmonary Disease Complicated by Pulmonary Hypertension
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Published
Aug 28, 2022
Abstract
As a chronic lung condition, chronic obstructive pulmonary disease (COPD) is well-known. As our understanding of COPD’s consequences has grown, pulmonary hypertension (PH) has drawn a growing amount of attention. Patients’ quality of life is significantly impacted by the higher mortality and poor prognosis of COPD patients with PH, and there are still no effective medications available to treat the condition. The development of medication therapy for COPD complicated by PH was examined in order to fully comprehend the state of the disease’s treatment at the moment. The findings suggest that for COPD patients with PH, the underlying disorders should be treated as well as possible. Statin and fasudil may also be advantageous, although the impact of targeted medications is still debatable. The effectiveness of various medications for COPD will eventually need to be further elucidated by larger randomized controlled studies.
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Keywords
Chronic Obstructive Pulmonary Disease, Pulmonary Hypertension, Pharmacology, Treatment, Outcomes
References
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7. Cassady SJ, Reed RM. Pulmonary hypertension in COPD: A case study and review of the literature. Medicina (Kaunas) 2019; 55(8):432. DOI: https://doi.org/10.3390/medicina55080432
8. Kent BD, Mitchell PD, McNicholas WT. Hypoxemia in patients with COPD: Cause, effects, and disease progression. Int J Chron Obstruct Pulmon Dis 2011; 6:199-208. DOI: https://doi.org/10.2147/COPD.S10611
9. Greenwood J, Mason JC. Statins and the vascular endothelial inflammatory response. Trends Immunol 2007; 28(2):88-98. DOI: https://doi.org/10.1016/j.it.2006.12.003
10. Margaritis M, Channon KM, Antoniades C. Statins as regulators of redox state in the vascular endothelium: Beyond lipid lowering. Antioxid Redox Signal 2014; 20(8):1198-1215. DOI: https://doi.org/10.1089/ars.2013.5430
11. Zhou Q, Liao JK. Statins and cardiovascular diseases: From cholesterol lowering to pleiotropy. Curr Pharm Des 2009; 15(5):467-478. DOI: https://doi.org/10.2174/138161209787315684
12. Kazi DS, Penko JM, Bibbins-Domingo K. Statins for primary prevention of cardiovascular disease: Review of evidence and recommendations for clinical practice. Med Clin North Am 2017; 101(4):689-699. DOI: https://doi.org/10.1016/j.mcna.2017.03.001
13. Lu Y, Chang R, Yao J, Xu X, Teng Y, Cheng N. Effectiveness of long-term using statins in COPD - A network meta-analysis. Respir Res 2019; 20(1):17. DOI: https://doi.org/10.1186/s12931-019-0984-3
14. Arif R, Pandey A, Zhao Y, Arsenault-Mehta K, Khoujah D, Mehta S. Treatment of pulmonary hypertension associated with COPD: A systematic review. ERJ Open Res 2022; 8(1):00348-2021. DOI: https://doi.org/10.1183/23120541.00348-2021
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16. Zhang MZ, Qian DH, Xu JC, Yao W, Fan Y, Wang CZ. Statins may be beneficial for patients with pulmonary hypertension secondary to lung diseases. J Thorac Dis 2017; 9(8):2437-2446. DOI: https://doi.org/10.21037/jtd.2017.07.06
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18. Zhang Y, Wu S. Effects of fasudil on pulmonary hypertension in clinical practice. Pulm Pharmacol Ther 2017; 46:54-63. DOI: https://doi.org/10.1016/j.pupt.2017.08.002
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20. Adir Y, Harari S. Pulmonary hypertension associated with chronic obstructive lung disease and idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 2014; 20(5):414-420. DOI: https://doi.org/10.1097/MCP.0000000000000084
21. Weiss A, Boehm M, Egemnazarov B, Grimminger F, Savai Pullamsetti S, Kwapiszewska G, Schermuly RT. Kinases as potential targets for treatment of pulmonary hypertension and right ventricular dysfunction. Br J Pharmacol 2021; 178(1):31-53. DOI: https://doi.org/10.1111/bph.14919
22. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M; ESC Scientific Document Group. 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 Heart J 2016; 37(1):67-119. DOI: https://doi.org/10.1093/eurheartj/ehv317
23. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 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. DOI: https://doi.org/10.1183/13993003.01032-2015. Erratum in: Eur Respir J 2015; 46(6):1855-1856.
24. Wang L, Jin YZ, Zhao QH, Jiang R, Wu WH, Gong SG, He J, Liu JM, Jing ZC. Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension. Int J Chron Obstruct Pulmon Dis 2017; 12:3353-3360. DOI: https://doi.org/10.2147/COPD.S141798
25. Boeck L, Tamm M, Grendelmeier P, Stolz D. Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - A randomized controlled crossover trial. PLoS One 2012; 7(12):e52248. DOI: https://doi.org/10.1371/journal.pone.0052248
26. Bajwa AA, Shujaat A, Patel M, Thomas C, Rahaghi F, Burger CD. The safety and tolerability of inhaled treprostinil in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Pulm Circ 2017; 7(1):82-88. DOI: https://doi.org/10.1086/689291
27. Richter MJ, Ghofrani HA, Voswinckel R, Seeger W, Schulz R, Reichenberger F, Gall H. Acute hemodynamic effects of nebulized iloprost via the I-neb Adaptive Aerosol Delivery system in pulmonary hypertension. Pulm Circ 2015; 5(1):162-170. DOI: https://doi.org/10.1086/679722
28. Enevoldsen FC, Sahana J, Wehland M, Grimm D, Infanger M, Krüger M. Endothelin receptor antagonists: Status quo and future perspectives for targeted therapy. J Clin Med 2020; 9(3):824. DOI: https://doi.org/10.3390/jcm9030824
29. Karami H, Darvishi-Khezri H, Kosaryan M, Akbarzadeh R, Dabirian M. The improvement of pulmonary artery pressure after bosentan therapy in patients with β-thalassemia and Doppler-defined pulmonary arterial hypertension. Int Med Case Rep J 2018; 12:1-7. DOI: https://doi.org/10.2147/IMCRJ.S180602
30. Badesch DB, Feldman J, Keogh A, Mathier MA, Oudiz RJ, Shapiro S, Farber HW, McGoon M, Frost A, Allard M, Despain D, Dufton C, Rubin LJ; ARIES-3 Study Group. ARIES-3: Ambrisentan therapy in a diverse population of patients with pulmonary hypertension. Cardiovasc Ther 2012; 30(2):93-99. DOI: https://doi.org/10.1111/j.1755-5922.2011.00279.x
31. Stolz D, Rasch H, Linka A, Di Valentino M, Meyer A, Brutsche M, Tamm M. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J 2008; 32(3):619-628. DOI: https://doi.org/10.1183/09031936.00011308
32. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H, Olsson KM, Peacock AJ, Pepke-Zaba J, Provencher S, Weissmann N, Seeger W. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019; 53(1):1801914. DOI: https://doi.org/10.1183/13993003.01914-2018
33. Ghofrani HA, Staehler G, Grünig E, Halank M, Mitrovic V, Unger S, Mueck W, Frey R, Grimminger F, Schermuly RT, Behr J. Acute effects of riociguat in borderline or manifest pulmonary hypertension associated with chronic obstructive pulmonary disease. Pulm Circ 2015; 5(2):296-304. DOI: https://doi.org/10.1086/680214
34. Ghofrani HA, Humbert M, Langleben D, Schermuly R, Stasch JP, Wilkins MR, Klinger JR. Riociguat: Mode of action and clinical development in pulmonary hypertension. Chest 2017;151(2):468-480. DOI: https://doi.org/10.1016/j.chest.2016.05.024
35. Pichl A, Sommer N, Bednorz M, Seimetz M, Hadzic S, Kuhnert S, Kraut S, Roxlau ET, Kojonazarov B, Wilhelm J, Gredic M, Gall H, Tello K, Richter MJ, Pak O, Petrovic A, Hecker M, Schermuly RT, Grimminger F, Seeger W, Ghofrani HA, Weissmann N. Riociguat for treatment of pulmonary hypertension in COPD: a translational study. Eur Respir J 2019; 53(6):1802445. DOI: https://doi.org/10.1183/13993003.02445-2018
36. Blanco I, Gimeno E, Munoz PA, Pizarro S, Gistau C, Rodriguez-Roisin R, Roca J, Barberà JA. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am J Respir Crit Care Med 2010; 181(3):270-278. DOI: https://doi.org/10.1164/rccm.200907-0988OC
37. Alp S, Skrygan M, Schmidt WE, Bastian A. Sildenafil improves hemodynamic parameters in COPD--an investigation of six patients. Pulm Pharmacol Ther 2006; 19(6):386-390. DOI: https://doi.org/10.1016/j.pupt.2005.09.006
38. Vitulo P, Stanziola A, Confalonieri M, Libertucci D, Oggionni T, Rottoli P, Paciocco G, Tuzzolino F, Martino L, Beretta M, Callari A, Amaducci A, Badagliacca R, Poscia R, Meloni F, Refini RM, Geri P, Baldi S, Ghio S, D'Alto M, Argiento P, Sofia M, Guardamagna M, Pezzuto B, Vizza CD. Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial. J Heart Lung Transplant 2017; 36(2):166-174. DOI: https://doi.org/10.1016/j.healun.2016.04.010
39. Barnes H, Brown Z, Burns A, Williams T. Phosphodiesterase 5 inhibitors for pulmonary hypertension. Cochrane Database Syst Rev 2019; 1(1):CD012621. DOI: https://doi.org/10.1002/14651858.CD012621.pub2
40. Vonbank K, Ziesche R, Higenbottam TW, Stiebellehner L, Petkov V, Schenk P, Germann P, Block LH. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax 2003; 58(4):289-293. DOI: https://doi.org/10.1136/thorax.58.4.289
41. Hajian B, De Backer J, Vos W, Van Holsbeke C, Ferreira F, Quinn DA, Hufkens A, Claes R, De Backer W. Pulmonary vascular effects of pulsed inhaled nitric oxide in COPD patients with pulmonary hypertension. Int J Chron Obstruct Pulmon Dis 2016; 11:1533-1541. DOI: https://doi.org/10.2147/COPD.S106480
2. Quaderi SA, Hurst JR. The unmet global burden of COPD. Glob Health Epidemiol Genom 2018; 3:e4. DOI: https://doi.org/10.1017/gheg.2018.1
3. Mandras SA, Mehta HS, Vaidya A. Pulmonary hypertension: A brief guide for clinicians. Mayo Clin Proc 2020; 95(9):1978-1988. DOI: https://doi.org/10.1016/j.mayocp.2020.04.039
4. Poch D, Mandel J. Pulmonary hypertension. Ann Intern Med 2021; 174(4):ITC49-ITC64. DOI: https://doi.org/10.7326/AITC202104200
5. Blanco I, Tura-Ceide O, Peinado VI, Barberà JA. Updated perspectives on pulmonary hypertension in COPD. Int J Chron Obstruct Pulmon Dis 2020; 15:1315-1324. DOI: https://doi.org/10.2147/COPD.S211841
6. Hurdman J, Condliffe R, Elliot CA, Davies C, Hill C, Wild JM, Capener D, Sephton P, Hamilton N, Armstrong IJ, Billings C, Lawrie A, Sabroe I, Akil M, O'Toole L, Kiely DG. ASPIRE registry: Assessing the spectrum of pulmonary hypertension identified at a REferral centre. Eur Respir J. 2012 Apr; 39(4):945-955. DOI: https://doi.org/10.1183/09031936.00078411s
7. Cassady SJ, Reed RM. Pulmonary hypertension in COPD: A case study and review of the literature. Medicina (Kaunas) 2019; 55(8):432. DOI: https://doi.org/10.3390/medicina55080432
8. Kent BD, Mitchell PD, McNicholas WT. Hypoxemia in patients with COPD: Cause, effects, and disease progression. Int J Chron Obstruct Pulmon Dis 2011; 6:199-208. DOI: https://doi.org/10.2147/COPD.S10611
9. Greenwood J, Mason JC. Statins and the vascular endothelial inflammatory response. Trends Immunol 2007; 28(2):88-98. DOI: https://doi.org/10.1016/j.it.2006.12.003
10. Margaritis M, Channon KM, Antoniades C. Statins as regulators of redox state in the vascular endothelium: Beyond lipid lowering. Antioxid Redox Signal 2014; 20(8):1198-1215. DOI: https://doi.org/10.1089/ars.2013.5430
11. Zhou Q, Liao JK. Statins and cardiovascular diseases: From cholesterol lowering to pleiotropy. Curr Pharm Des 2009; 15(5):467-478. DOI: https://doi.org/10.2174/138161209787315684
12. Kazi DS, Penko JM, Bibbins-Domingo K. Statins for primary prevention of cardiovascular disease: Review of evidence and recommendations for clinical practice. Med Clin North Am 2017; 101(4):689-699. DOI: https://doi.org/10.1016/j.mcna.2017.03.001
13. Lu Y, Chang R, Yao J, Xu X, Teng Y, Cheng N. Effectiveness of long-term using statins in COPD - A network meta-analysis. Respir Res 2019; 20(1):17. DOI: https://doi.org/10.1186/s12931-019-0984-3
14. Arif R, Pandey A, Zhao Y, Arsenault-Mehta K, Khoujah D, Mehta S. Treatment of pulmonary hypertension associated with COPD: A systematic review. ERJ Open Res 2022; 8(1):00348-2021. DOI: https://doi.org/10.1183/23120541.00348-2021
15. Arian A, Moghadam SG, Kazemi T, Hajihosseini M. The effects of statins on pulmonary artery pressure in patients with chronic obstructive pulmonary disease: A randomized controlled trial. J Res Pharm Pract 2017; 6(1):27-30. DOI: https://doi.org/10.4103/2279-042X.200985
16. Zhang MZ, Qian DH, Xu JC, Yao W, Fan Y, Wang CZ. Statins may be beneficial for patients with pulmonary hypertension secondary to lung diseases. J Thorac Dis 2017; 9(8):2437-2446. DOI: https://doi.org/10.21037/jtd.2017.07.06
17. Wu WT, Chen CY. Protective effect of statins on pulmonary hypertension in chronic obstructive pulmonary disease patients: A nationwide retrospective, matched cohort study. Sci Rep 2020; 10(1):3104. DOI: https://doi.org/10.1038/s41598-020-59828-0
18. Zhang Y, Wu S. Effects of fasudil on pulmonary hypertension in clinical practice. Pulm Pharmacol Ther 2017; 46:54-63. DOI: https://doi.org/10.1016/j.pupt.2017.08.002
19. Liu P, Zhang HM, Tang YJ, Sheng CF, Liu JX, Zeng YJ. Influence of Rho kinase inhibitor fasudil on late endothelial progenitor cells in peripheral blood of COPD patients with pulmonary artery hypertension. Bratisl Lek Listy 2015; 116(3):150-153. DOI: https://doi.org/10.4149/bll_2015_030
20. Adir Y, Harari S. Pulmonary hypertension associated with chronic obstructive lung disease and idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 2014; 20(5):414-420. DOI: https://doi.org/10.1097/MCP.0000000000000084
21. Weiss A, Boehm M, Egemnazarov B, Grimminger F, Savai Pullamsetti S, Kwapiszewska G, Schermuly RT. Kinases as potential targets for treatment of pulmonary hypertension and right ventricular dysfunction. Br J Pharmacol 2021; 178(1):31-53. DOI: https://doi.org/10.1111/bph.14919
22. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M; ESC Scientific Document Group. 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 Heart J 2016; 37(1):67-119. DOI: https://doi.org/10.1093/eurheartj/ehv317
23. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 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. DOI: https://doi.org/10.1183/13993003.01032-2015. Erratum in: Eur Respir J 2015; 46(6):1855-1856.
24. Wang L, Jin YZ, Zhao QH, Jiang R, Wu WH, Gong SG, He J, Liu JM, Jing ZC. Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension. Int J Chron Obstruct Pulmon Dis 2017; 12:3353-3360. DOI: https://doi.org/10.2147/COPD.S141798
25. Boeck L, Tamm M, Grendelmeier P, Stolz D. Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - A randomized controlled crossover trial. PLoS One 2012; 7(12):e52248. DOI: https://doi.org/10.1371/journal.pone.0052248
26. Bajwa AA, Shujaat A, Patel M, Thomas C, Rahaghi F, Burger CD. The safety and tolerability of inhaled treprostinil in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Pulm Circ 2017; 7(1):82-88. DOI: https://doi.org/10.1086/689291
27. Richter MJ, Ghofrani HA, Voswinckel R, Seeger W, Schulz R, Reichenberger F, Gall H. Acute hemodynamic effects of nebulized iloprost via the I-neb Adaptive Aerosol Delivery system in pulmonary hypertension. Pulm Circ 2015; 5(1):162-170. DOI: https://doi.org/10.1086/679722
28. Enevoldsen FC, Sahana J, Wehland M, Grimm D, Infanger M, Krüger M. Endothelin receptor antagonists: Status quo and future perspectives for targeted therapy. J Clin Med 2020; 9(3):824. DOI: https://doi.org/10.3390/jcm9030824
29. Karami H, Darvishi-Khezri H, Kosaryan M, Akbarzadeh R, Dabirian M. The improvement of pulmonary artery pressure after bosentan therapy in patients with β-thalassemia and Doppler-defined pulmonary arterial hypertension. Int Med Case Rep J 2018; 12:1-7. DOI: https://doi.org/10.2147/IMCRJ.S180602
30. Badesch DB, Feldman J, Keogh A, Mathier MA, Oudiz RJ, Shapiro S, Farber HW, McGoon M, Frost A, Allard M, Despain D, Dufton C, Rubin LJ; ARIES-3 Study Group. ARIES-3: Ambrisentan therapy in a diverse population of patients with pulmonary hypertension. Cardiovasc Ther 2012; 30(2):93-99. DOI: https://doi.org/10.1111/j.1755-5922.2011.00279.x
31. Stolz D, Rasch H, Linka A, Di Valentino M, Meyer A, Brutsche M, Tamm M. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J 2008; 32(3):619-628. DOI: https://doi.org/10.1183/09031936.00011308
32. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H, Olsson KM, Peacock AJ, Pepke-Zaba J, Provencher S, Weissmann N, Seeger W. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019; 53(1):1801914. DOI: https://doi.org/10.1183/13993003.01914-2018
33. Ghofrani HA, Staehler G, Grünig E, Halank M, Mitrovic V, Unger S, Mueck W, Frey R, Grimminger F, Schermuly RT, Behr J. Acute effects of riociguat in borderline or manifest pulmonary hypertension associated with chronic obstructive pulmonary disease. Pulm Circ 2015; 5(2):296-304. DOI: https://doi.org/10.1086/680214
34. Ghofrani HA, Humbert M, Langleben D, Schermuly R, Stasch JP, Wilkins MR, Klinger JR. Riociguat: Mode of action and clinical development in pulmonary hypertension. Chest 2017;151(2):468-480. DOI: https://doi.org/10.1016/j.chest.2016.05.024
35. Pichl A, Sommer N, Bednorz M, Seimetz M, Hadzic S, Kuhnert S, Kraut S, Roxlau ET, Kojonazarov B, Wilhelm J, Gredic M, Gall H, Tello K, Richter MJ, Pak O, Petrovic A, Hecker M, Schermuly RT, Grimminger F, Seeger W, Ghofrani HA, Weissmann N. Riociguat for treatment of pulmonary hypertension in COPD: a translational study. Eur Respir J 2019; 53(6):1802445. DOI: https://doi.org/10.1183/13993003.02445-2018
36. Blanco I, Gimeno E, Munoz PA, Pizarro S, Gistau C, Rodriguez-Roisin R, Roca J, Barberà JA. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am J Respir Crit Care Med 2010; 181(3):270-278. DOI: https://doi.org/10.1164/rccm.200907-0988OC
37. Alp S, Skrygan M, Schmidt WE, Bastian A. Sildenafil improves hemodynamic parameters in COPD--an investigation of six patients. Pulm Pharmacol Ther 2006; 19(6):386-390. DOI: https://doi.org/10.1016/j.pupt.2005.09.006
38. Vitulo P, Stanziola A, Confalonieri M, Libertucci D, Oggionni T, Rottoli P, Paciocco G, Tuzzolino F, Martino L, Beretta M, Callari A, Amaducci A, Badagliacca R, Poscia R, Meloni F, Refini RM, Geri P, Baldi S, Ghio S, D'Alto M, Argiento P, Sofia M, Guardamagna M, Pezzuto B, Vizza CD. Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial. J Heart Lung Transplant 2017; 36(2):166-174. DOI: https://doi.org/10.1016/j.healun.2016.04.010
39. Barnes H, Brown Z, Burns A, Williams T. Phosphodiesterase 5 inhibitors for pulmonary hypertension. Cochrane Database Syst Rev 2019; 1(1):CD012621. DOI: https://doi.org/10.1002/14651858.CD012621.pub2
40. Vonbank K, Ziesche R, Higenbottam TW, Stiebellehner L, Petkov V, Schenk P, Germann P, Block LH. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax 2003; 58(4):289-293. DOI: https://doi.org/10.1136/thorax.58.4.289
41. Hajian B, De Backer J, Vos W, Van Holsbeke C, Ferreira F, Quinn DA, Hufkens A, Claes R, De Backer W. Pulmonary vascular effects of pulsed inhaled nitric oxide in COPD patients with pulmonary hypertension. Int J Chron Obstruct Pulmon Dis 2016; 11:1533-1541. DOI: https://doi.org/10.2147/COPD.S106480
How to Cite
Karyana, L. (2022). Pharmaceutical Therapies for Chronic Obstructive Pulmonary Disease Complicated by Pulmonary Hypertension. Science Insights, 41(3), 639–644. https://doi.org/10.15354/si.22.re078
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