Key Points
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In the Western world, idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH) are the most common subtypes of PAH; PAH is increasingly diagnosed in an ageing population with comorbidities
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The aetiology of PAH is distinct in the developing world; congenital heart disease-associated PAH is the most common form in China, whereas infectious causes such as schistosomiasis is common in countries such as Brazil
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PAH registries worldwide continue to report improvement in survival with the use of current PAH therapy
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Five classes of drugs are now approved for the treatment of PAH, including endothelin 1 receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin IP receptor agonist
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Combination therapy is currently considered standard of care in PAH, and evidence supports the early and aggressive use of combination therapy at the time of diagnosis
Abstract
In the past 2 decades, major changes have occurred in the epidemiological and treatment landscape of pulmonary arterial hypertension (PAH). Previously regarded as a disease of the young and middle-aged, contemporary registries from the Western world have demonstrated an increase in the age of patients with PAH, many of whom are elderly with multiple comorbidities. Another important observation is the improvement in survival of patients with PAH in the modern treatment era compared with historical cohorts, before the availability of advanced therapy. The management of PAH has also become more complex, and numerous drugs are now approved that target the endothelin 1, nitric oxide, and prostacyclin pathways. Combining drugs from different classes is now considered the standard of care and has been demonstrated to improve outcomes. Furthermore, the current treatment paradigm is the early use of combination therapy, often at the time of diagnosis, particularly in patients with severe disease. This Review provides a comprehensive update on the epidemiology and pharmacotherapy of PAH.
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References
Humbert, M. et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 43, 13S–24S (2004).
Humbert, M. et al. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation 130, 2189–2208 (2014).
Tonelli, A. R. et al. Causes and circumstances of death in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 188, 365–369 (2013).
Vonk-Noordegraaf, A. et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J. Am. Coll. Cardiol. 62, D22–D33 (2013).
Simonneau, G. et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 62, D34–D41 (2013).
Galie, N. 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). Eur. Respir. J. 46, 903–975 (2015).
Hoeper, M. M. et al. Definitions and diagnosis of pulmonary hypertension. J. Am. Coll. Cardiol. 62, D42–50 (2013).
Peacock, A. J. et al. An epidemiological study of pulmonary arterial hypertension. Eur. Respir. J. 30, 104–109 (2007).
Humbert, M. et al. Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. 173, 1023–1030 (2006).
Ling, Y. et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am. J. Respir. Crit. Care Med. 186, 790–796 (2012).
Strange, G. et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart 98, 1805–1811 (2012).
D'Alonzo, G. E. et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann. Intern. Med. 115, 343–349 (1991).
Rich, S. et al. Primary pulmonary hypertension. A national prospective study. Ann. Intern. Med. 107, 216–223 (1987).
Humbert, M. et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 122, 156–163 (2010).
Thenappan, T. et al. A USA-based registry for pulmonary arterial hypertension: 1982–2006. Eur. Respir. J. 30, 1103–1110 (2007).
Thenappan, T. et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur. Respir. J. 35, 1079–1087 (2010).
Badesch, D. B. et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 137, 376–387 (2010).
Benza, R. L. et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest 142, 448–456 (2012).
Escribano-Subias, P. et al. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur. Respir. J. 40, 596–603 (2012).
Jiang, X., Humbert, M. & Jing, Z. C. in Pulmonary Vascular Disorders Vol. 41 (eds Humbert, M., Souza, R. & Simonneau, G.) 85–93 (Karger, 2012).
Jing, Z. C. et al. Registry and survival study in chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest 132, 373–379 (2007).
Hoeper, M. M. et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int. J. Cardiol. 168, 871–880 (2013).
Ogawa, A. et al. Survival of Japanese patients with idiopathic/heritable pulmonary arterial hypertension. Am. J. Cardiol. 119, 1479–1484 (2017).
Chung, W. J. et al. Baseline characteristics of the Korean Registry of Pulmonary Arterial Hypertension. J. Korean Med. Sci. 30, 1429–1438 (2015).
Jansa, P. et al. Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry. BMC Pulm. Med. 14, 45 (2014).
Alves, J. L. Jr et al. Pulmonary arterial hypertension in the southern hemisphere: results from a registry of incident Brazilian cases. Chest 147, 495–501 (2015).
Mueller-Mottet, S. et al. Long-term data from the Swiss pulmonary hypertension registry. Respiration 89, 127–140 (2015).
Zhang, R. et al. Survival of Chinese patients with pulmonary arterial hypertension in the modern treatment era. Chest 140, 301–309 (2011).
Lee, W. T. et al. Predicting survival in pulmonary arterial hypertension in the UK. Eur. Respir. J. 40, 604–611 (2012).
McGoon, M. D. et al. Pulmonary arterial hypertension: epidemiology and registries. J. Am. Coll. Cardiol. 62, D51–D59 (2013).
Hoeper, M. M. & Simon, R. G. J. The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur. Respir. Rev. 23, 450–457 (2014).
Poms, A. D. et al. Comorbid conditions and outcomes in patients with pulmonary arterial hypertension: a REVEAL registry analysis. Chest 144, 169–176 (2013).
Halpern, S. D. & Taichman, D. B. Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure. Chest 136, 37–43 (2009).
Larkin, E. K. et al. Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 186, 892–896 (2012).
Benza, R. L. et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 141, 354–362 (2012).
Kawut, S. M. et al. Sex and race differences in right ventricular structure and function: the multi-ethnic study of atherosclerosis-right ventricle study. Circulation 123, 2542–2551 (2011).
Jacobs, W. et al. The right ventricle explains sex differences in survival in idiopathic pulmonary arterial hypertension. Chest 145, 1230–1236 (2014).
Sitbon, O. et al. Initial dual oral combination therapy in pulmonary arterial hypertension. Eur. Respir. J. 47, 1727–1736 (2016).
Gall, H. et al. The Giessen Pulmonary Hypertension Registry: survival in pulmonary hypertension subgroups. J. Heart Lung Transplant. http://dx.doi.org/10.1016/j.healun.2017.02.016 (2017).
Benza, R. L. 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 122, 164–172 (2010).
Evans, J. D. et al. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir. Med. 4, 129–137 (2016).
Montani, D. et al. Clinical phenotypes and outcomes of heritable and sporadic pulmonary veno-occlusive disease: a population-based study. Lancet Respir. Med. 5, 125–134 (2017).
Tamby, M. C. et al. Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax 60, 765–772 (2005).
Humbert, M. et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur. Respir. J. 36, 549–555 (2010).
Sitbon, O. et al. Validation of two predictive models for survival in pulmonary arterial hypertension. Eur. Respir. J. 46, 152–164 (2015).
Giaid, A. et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 328, 1732–1739 (1993).
Giaid, A. & Saleh, D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 333, 214–221 (1995).
Humbert, M., Sitbon, O. & Simonneau, G. Treatment of pulmonary arterial hypertension. N. Engl. J. Med. 351, 1425–1436 (2004).
Guignabert, C. et al. New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension: importance of endothelial communication. Chest 147, 529–537 (2015).
Morrell, N. W. et al. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-β1 and bone morphogenetic proteins. Circulation 104, 790–795 (2001).
Humbert, M. et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am. J. Respir. Crit. Care Med. 151, 1628–1631 (1995).
Price, L. C. et al. Inflammation in pulmonary arterial hypertension. Chest 141, 210–221 (2012).
Perros, F. et al. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 185, 311–321 (2012).
McMurtry, M. S. et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ. Res. 95, 830–840 (2004).
Zhao, L. et al. Heterogeneity in lung 18FDG uptake in pulmonary arterial hypertension: potential of dynamic 18FDG positron emission tomography with kinetic analysis as a bridging biomarker for pulmonary vascular remodeling targeted treatments. Circulation 128, 1214–1224 (2013).
Perros, F. et al. Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 178, 81–88 (2008).
Tu, L. et al. Autocrine fibroblast growth factor-2 signaling contributes to altered endothelial phenotype in pulmonary hypertension. Am. J. Respir. Cell Mol. Biol. 45, 311–322 (2011).
Guignabert, C. et al. Pathogenesis of pulmonary arterial hypertension: lessons from cancer. Eur. Respir. Rev. 22, 543–551 (2013).
Yuan, J. X. et al. Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 98, 1400–1406 (1998).
Antigny, F. et al. Potassium channel subfamily K member 3 (KCNK3) contributes to the development of pulmonary arterial hypertension. Circulation 133, 1371–1385 (2016).
Machado, R. D. et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am. J. Hum. Genet. 68, 92–102 (2001).
Ma, L. et al. A novel channelopathy in pulmonary arterial hypertension. N. Engl. J. Med. 369, 351–361 (2013).
Soubrier, F. et al. Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 62, D13–D21 (2013).
Humbert, M. & Ghofrani, H. A. The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax 71, 73–83 (2016).
Galie, N. et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N. Engl. J. Med. 373, 834–844 (2015).
Davie, N. et al. ETA and ETB receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am. J. Respir. Crit. Care Med. 165, 398–405 (2002).
Hirata, Y. et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J. Clin. Invest. 91, 1367–1373 (1993).
Rubin, L. J. et al. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. 346, 896–903 (2002).
Humbert, M. et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur. Respir. J. 30, 338–344 (2007).
Galie, N. et al. Ambrisentan therapy for pulmonary arterial hypertension. J. Am. Coll. Cardiol. 46, 529–535 (2005).
Galie, N. 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 117, 3010–3019 (2008).
Iglarz, M. et al. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J. Pharmacol. Exp. Ther. 327, 736–745 (2008).
Pulido, T. et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N. Engl. J. Med. 369, 809–818 (2013).
Rybalkin, S. D. et al. Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ. Res. 93, 280–291 (2003).
Galie, N. et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med. 353, 2148–2157 (2005).
Rubin, L. J. et al. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study. Chest 140, 1274–1283 (2011).
Galie, N. et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation 119, 2894–2903 (2009).
Stasch, J. P. et al. NO-independent regulatory site on soluble guanylate cyclase. Nature 410, 212–215 (2001).
Stasch, J. P., Pacher, P. & Evgenov, O. V. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation 123, 2263–2273 (2011).
Ghofrani, H. A. et al. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 369, 330–340 (2013).
Humbert, M. et al. Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann. Rheum. Dis. 76, 422–426 (2017).
Ghofrani, H. A. et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N. Engl. J. Med. 369, 319–329 (2013).
Olschewski, H. et al. Cellular pathophysiology and therapy of pulmonary hypertension. J. Lab. Clin. Med. 138, 367–377 (2001).
Coleman, R. A., Smith, W. L. & Narumiya, S. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol. Rev. 46, 205–229 (1994).
Barst, R. J. et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N. Engl. J. Med. 334, 296–301 (1996).
Sitbon, O. et al. EPITOME-2: an open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension. Am. Heart J. 167, 210–217 (2014).
Jing, Z. C. et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation 127, 624–633 (2013).
McLaughlin, V. V. et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J. Am. Coll. Cardiol. 55, 1915–1922 (2010).
Asaki, T. et al. Selexipag: an oral and selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. J. Med. Chem. 58, 7128–7137 (2015).
Sitbon, O. et al. Selexipag for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 373, 2522–2533 (2015).
European Medicines Agency. EMA concludes safety review of Uptravi. EMA http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2017/04/news_detail_002726.jsp&mid=WC0b01ac058004d5c1 (2017).
Barst, R. J. et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54, S78–S84 (2009).
McLaughlin, V. V. et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 174, 1257–1263 (2006).
Hoeper, M. M. et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 28, 691–694 (2006).
Simonneau, G. et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann. Intern. Med. 149, 521–530 (2008).
Tapson, V. 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 142, 1383–1390 (2012).
Tapson, V. F. 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 144, 952–958 (2013).
McLaughlin, V. et al. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur. Respir. J. 46, 405–413 (2015).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00323297 (2014).
Lajoie, A. C. et al. Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis. Lancet Respir. Med. 4, 291–305 (2016).
Galie, N. et al. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur. Respir. J. 45, 1314–1322 (2015).
Humbert, M. et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur. Respir. J. 24, 353–359 (2004).
Coghlan, J. G. 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. http://dx.doi.org/10.1136/annrheumdis-2016-210236 (2016).
Galie, N. et al. AMBITION: a randomised, multicentre study of first line ambrisentan and tadalafil combination therapy in subjects with pulmonary arterial hypertension (PAH). Eur. Respir. J. 44, A2916 (2014).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02558231 (2016).
Hassoun, P. M. et al. Ambrisentan and tadalafil up-front combination therapy in scleroderma-associated pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 192, 1102–1110 (2015).
Sitbon, O. et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur. Respir. J. 43, 1691–1697 (2014).
Rosenkranz, S. et al. Left ventricular heart failure and pulmonary hypertension. Eur. Heart J. 37, 942–954 (2016).
Opitz, C. F. et al. Pre-capillary, combined, and post-capillary pulmonary hypertension: a pathophysiological continuum. J. Am. Coll. Cardiol. 68, 368–378 (2016).
Charalampopoulos, A. et al. Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors. Pulm. Circ. 4, 669–678 (2014).
van Campen, J. S. et al. Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study. Eur. Respir. J. 48, 787–796 (2016).
Gomez-Arroyo, J. et al. Treatment for pulmonary arterial hypertension-associated right ventricular dysfunction. Ann. Am. Thorac Soc. 11, 1101–1115 (2014).
Mathai, S. C. et al. Tricuspid annular plane systolic excursion is a robust outcome measure in systemic sclerosis-associated pulmonary arterial hypertension. J. Rheumatol. 38, 2410–2418 (2011).
Forfia, P. R. et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 174, 1034–1041 (2006).
van Wolferen, S. A. et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur. Heart J. 28, 1250–1257 (2007).
van de Veerdonk, M. C. et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J. Am. Coll. Cardiol. 58, 2511–2519 (2011).
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E.M.T.L. and M.H. researched the data for the article, and E.M.T.L. wrote the manuscript. All the authors made substantial contributions to discussion of content, and edited/reviewed the manuscript before submission.
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E.M.T.L. has relationships with Actelion, AstraZeneca, GSK, and Menarini. Relationships include serving on speaker bureaus, consultancy on advisory boards, and research funding support. D.S.C. received support from Actelion, including serving on the speaker bureau and funding for research. M.H. has relationships with drug companies including Actelion, Bayer, GSK, Merck, Novartis, Pfizer, and United Therapeutics. In addition to being an investigator in trials involving these companies, relationships include consultancy service and membership of scientific advisory boards. E.G. declares no competing interests.
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Lau, E., Giannoulatou, E., Celermajer, D. et al. Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol 14, 603–614 (2017). https://doi.org/10.1038/nrcardio.2017.84
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DOI: https://doi.org/10.1038/nrcardio.2017.84
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