{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:40:47Z","timestamp":1792006847623,"version":"4.4.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2019,10]]},"DOI":"10.1007\/s12325-019-01052-y","type":"journal-article","created":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T08:02:32Z","timestamp":1565424152000},"page":"2910-2926","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cardiovascular Risks, Bleeding Risks, and Clinical Events from 3 Phase III Trials of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis"],"prefix":"10.1007","volume":"36","author":[{"given":"Marilyn K.","family":"Glassberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Nathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Morgenthien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Stauffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willis","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Noble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,10]]},"reference":[{"issue":"1","key":"1052_CR1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1378\/chest.09-1002","volume":"137","author":"ER Fernandez Perez","year":"2010","unstructured":"Fernandez Perez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE, Bartholmai BJ, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010;137(1):129\u201337.","journal-title":"Chest"},{"issue":"1","key":"1052_CR2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1378\/chest.10-2572","volume":"140","author":"SD Nathan","year":"2011","unstructured":"Nathan SD, Shlobin OA, Weir N, Ahmad S, Kaldjob JM, Battle E, et al. Long-term course and prognosis of idiopathic pulmonary fibrosis in the new millennium. Chest. 2011;140(1):221\u20139.","journal-title":"Chest"},{"issue":"6","key":"1052_CR3","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1164\/rccm.2009-040GL","volume":"183","author":"G Raghu","year":"2011","unstructured":"Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS\/ERS\/JRS\/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788\u2013824.","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"1052_CR4","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3322\/caac.21349","volume":"66","author":"KD Miller","year":"2016","unstructured":"Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics. CA Cancer J Clin. 2016;66(4):271\u201389.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"1052_CR5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1165\/rcmb.2016-0217OC","volume":"57","author":"L Knuppel","year":"2017","unstructured":"Knuppel L, Ishikawa Y, Aichler M, Heinzelmann K, Hatz R, Behr J, et al. A novel antifibrotic mechanism of nintedanib and pirfenidone. Inhibition of collagen fibril assembly. Am J Respir Cell Mol Biol. 2017;57(1):77\u201390.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"120","key":"1052_CR6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1183\/09059180.00001111","volume":"20","author":"CJ Schaefer","year":"2011","unstructured":"Schaefer CJ, Ruhrmund DW, Pan L, Seiwert SD, Kossen K. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev. 2011;20(120):85\u201397.","journal-title":"Eur Respir Rev"},{"issue":"5","key":"1052_CR7","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1183\/09031936.00174914","volume":"45","author":"L Wollin","year":"2015","unstructured":"Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1434\u201345.","journal-title":"Eur Respir J"},{"issue":"1","key":"1052_CR8","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1378\/chest.14-0041","volume":"147","author":"W Dalleywater","year":"2015","unstructured":"Dalleywater W, Powell HA, Hubbard RB, Navaratnam V. Risk factors for cardiovascular disease in people with idiopathic pulmonary fibrosis: a population-based study. Chest. 2015;147(1):150\u20136.","journal-title":"Chest"},{"issue":"7","key":"1052_CR9","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.rmed.2010.02.008","volume":"104","author":"SD Nathan","year":"2010","unstructured":"Nathan SD, Basavaraj A, Reichner C, Shlobin OA, Ahmad S, Kiernan J, et al. Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis. Respir Med. 2010;104(7):1035\u201341.","journal-title":"Respir Med"},{"issue":"12","key":"1052_CR10","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1164\/rccm.200805-725OC","volume":"178","author":"RB Hubbard","year":"2008","unstructured":"Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008;178(12):1257\u201361.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"1052_CR11","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12931-017-0642-6","volume":"18","author":"M Karkkainen","year":"2017","unstructured":"Karkkainen M, Kettunen HP, Nurmi H, Selander T, Purokivi M, Kaarteenaho R. Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis. Respir Res. 2017;18(1):160.","journal-title":"Respir Res"},{"issue":"4","key":"1052_CR12","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1183\/13993003.02316-2014","volume":"46","author":"G Raghu","year":"2015","unstructured":"Raghu G, Amatto VC, Behr J, Stowasser S. Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review. Eur Respir J. 2015;46(4):1113\u201330.","journal-title":"Eur Respir J"},{"issue":"5","key":"1052_CR13","doi-asserted-by":"publisher","first-page":"829","DOI":"10.3111\/13696998.2012.680553","volume":"15","author":"HR Collard","year":"2012","unstructured":"Collard HR, Ward AJ, Lanes S, Cortney Hayflinger D, Rosenberg DM, Hunsche E. Burden of illness in idiopathic pulmonary fibrosis. J Med Econ. 2012;15(5):829\u201335.","journal-title":"J Med Econ."},{"issue":"3","key":"1052_CR14","doi-asserted-by":"publisher","first-page":"e0151425","DOI":"10.1371\/journal.pone.0151425","volume":"11","author":"M Kreuter","year":"2016","unstructured":"Kreuter M, Ehlers-Tenenbaum S, Palmowski K, Bruhwyler J, Oltmanns U, Muley T, et al. Impact of comorbidities on mortality in patients with idiopathic pulmonary fibrosis. PLoS One. 2016;11(3):e0151425.","journal-title":"PLoS One"},{"issue":"2","key":"1052_CR15","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1136\/thoraxjnl-2016-208819","volume":"72","author":"M Kreuter","year":"2017","unstructured":"Kreuter M, Bonella F, Maher TM, Costabel U, Spagnolo P, Weycker D, et al. Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis. Thorax. 2017;72(2):148\u201353.","journal-title":"Thorax"},{"issue":"1","key":"1052_CR16","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1164\/rccm.201202-0314OC","volume":"186","author":"I Noth","year":"2012","unstructured":"Noth I, Anstrom KJ, Calvert SB, de Andrade J, Flaherty KR, Glazer C, et al. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;186(1):88\u201395.","journal-title":"Am J Respir Crit Care Med"},{"key":"1052_CR17","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1183\/13993003.01482-2016","volume":"48","author":"M Kreuter","year":"2016","unstructured":"Kreuter M, Wijsenbeek MS, Vasakova M, Spagnolo P, Kolb M, Costabel U, et al. Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis: methodological concerns. Eur Respir J. 2016;48:1524\u20138.","journal-title":"Eur Respir J"},{"issue":"2","key":"1052_CR18","first-page":"121","volume":"30","author":"S Tomassetti","year":"2013","unstructured":"Tomassetti S, Ruy JH, Gurioli C, Ravaglia C, Buccioli M, Tantalocco P, et al. The effect of anticoagulant therapy for idiopathic pulmonary fibrosis in real life practice. Sarcoidosis, vasculitis, and diffuse lung dis. 2013;30(2):121\u20137.","journal-title":"Sarcoidosis, vasculitis, and diffuse lung dis"},{"key":"1052_CR19","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1164\/rccm.201511-2267LE","volume":"193","author":"GA Margaritopolous","year":"2016","unstructured":"Margaritopolous GA, Antoniou KM. Can warfarin be used in the treatment of pulmonary embolism in idiopathic pulmonary fibrosis? Am J Respir Crit Care Med. 2016;193:810\u20131.","journal-title":"Am J Respir Crit Care Med"},{"issue":"22","key":"1052_CR20","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1056\/NEJMoa1402582","volume":"370","author":"TE King Jr","year":"2014","unstructured":"King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083\u201392.","journal-title":"N Engl J Med"},{"issue":"9779","key":"1052_CR21","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/S0140-6736(11)60405-4","volume":"377","author":"PW Noble","year":"2011","unstructured":"Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760\u20139.","journal-title":"Lancet"},{"issue":"5","key":"1052_CR22","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1007\/s12350-015-0209-1","volume":"22","author":"KA Hicks","year":"2015","unstructured":"Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, et al. 2014 ACC\/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Nucl Cardiol. 2015;22(5):1041\u2013144.","journal-title":"J Nucl Cardiol."},{"issue":"4","key":"1052_CR23","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.ahj.2015.01.007","volume":"169","author":"PT Sager","year":"2015","unstructured":"Sager PT, Seltzer J, Turner JR, Anderson JL, Hiatt WR, Kowey P, et al. Cardiovascular Safety Outcome Trials: a meeting report from the Cardiac Safety Research Consortium. Am Heart J. 2015;169(4):486\u201395.","journal-title":"Am Heart J"},{"issue":"2","key":"1052_CR24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.ahj.2014.11.003","volume":"169","author":"JH Seltzer","year":"2015","unstructured":"Seltzer JH, Turner JR, Geiger MJ, Rosano G, Mahaffey KW, White WB, et al. Centralized adjudication of cardiovascular end points in cardiovascular and noncardiovascular pharmacologic trials: a report from the Cardiac Safety Research Consortium. Am Heart J. 2015;169(2):197\u2013204.","journal-title":"Am Heart J"},{"key":"1052_CR25","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1378\/chest.14-2817","volume":"148","author":"DJ Lederer","year":"2015","unstructured":"Lederer DJ, Bradford WZ, Fagan EA, Glaspole I, Glassberg MK, Glasscock KF, et al. Sensitivity analyses of the change in forced vital capacity in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis. Chest. 2015;148:196\u2013201.","journal-title":"Chest"},{"issue":"557","key":"1052_CR26","first-page":"572","volume":"80","author":"DY Lin","year":"1993","unstructured":"Lin DY, Wei LJ, Ying Z. Checking the Cox model with cumulative sums of martingale-based residuals. Biometrika. 1993;80(557):572.","journal-title":"Biometrika"},{"issue":"1","key":"1052_CR27","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1183\/09031936.00217614","volume":"46","author":"J Behr","year":"2015","unstructured":"Behr J, Kreuter M, Hoeper MM, Wirtz H, Klotsche J, Koschel D, et al. Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry. Eur Respir J. 2015;46(1):186\u201396.","journal-title":"Eur Respir J."},{"issue":"1","key":"1052_CR28","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1183\/09031936.00036815","volume":"46","author":"V Cottin","year":"2015","unstructured":"Cottin V, Wuyts W. Insights into idiopathic pulmonary fibrosis in the real world. Eur Respir J. 2015;46(1):16\u20138.","journal-title":"Eur Respir J."},{"issue":"1","key":"1052_CR29","doi-asserted-by":"publisher","first-page":"e000108","DOI":"10.1136\/bmjresp-2015-000108","volume":"3","author":"EC O\u2019Brien","year":"2016","unstructured":"O\u2019Brien EC, Durheim MT, Gamerman V, Garfinkel S, Anstrom KJ, Palmer SM, et al. Rationale for and design of the idiopathic pulmonary fibrosis-PRospective outcomes (IPF-PRO) registry. BMJ Open Respir Res. 2016;3(1):e000108.","journal-title":"BMJ Open Respir Res"},{"issue":"10","key":"1052_CR30","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1001\/archinte.159.10.1104","volume":"159","author":"PW Wilson","year":"1999","unstructured":"Wilson PW, Kannel WB, Silbershatz H, D\u2019Agostino RB. Clustering of metabolic factors and coronary heart disease. Arch Intern Med. 1999;159(10):1104\u20139.","journal-title":"Arch Intern Med"},{"issue":"4","key":"1052_CR31","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1056\/NEJMoa1012848","volume":"366","author":"JD Berry","year":"2012","unstructured":"Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366(4):321\u20139.","journal-title":"N Engl J Med"},{"key":"1052_CR32","first-page":"e13","volume":"71","author":"PK Whelton","year":"2017","unstructured":"Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;71:e13\u2013115.","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"1052_CR33","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1164\/rccm.201506-1063ST","volume":"192","author":"G Raghu","year":"2015","unstructured":"Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, et al. An official ATS\/ERS\/JRS\/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3\u201319.","journal-title":"Am J Respir Crit Care Med"},{"key":"1052_CR34","first-page":"A2695","volume":"193","author":"L Lancaster","year":"2016","unstructured":"Lancaster L, Morrison L, Auais A, Ding B, Iqbal A, Flaherty K. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis in a US expanded access program. Am J Respir Crit Care Med. 2016;193:A2695.","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"1052_CR35","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1111\/resp.12297","volume":"19","author":"D Valeyre","year":"2014","unstructured":"Valeyre D, Albera C, Bradford WZ, Costabel U, King TE Jr, Leff JA, et al. Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Respirology (Carlton, Vic). 2014;19(5):740\u20137.","journal-title":"Respirology (Carlton, Vic)."},{"key":"1052_CR36","doi-asserted-by":"publisher","first-page":"40523","DOI":"10.1038\/srep40523","volume":"7","author":"C Li","year":"2017","unstructured":"Li C, Han R, Kang L, Wang J, Gao Y, Li Y, et al. Pirfenidone controls the feedback loop of the AT1R\/p38 MAPK\/renin-angiotensin system axis by regulating liver X receptor-alpha in myocardial infarction-induced cardiac fibrosis. Sci Rep. 2017;7:40523.","journal-title":"Sci Rep."},{"key":"1052_CR37","unstructured":"Ofev (nintedanib) capsules, for oral use [package insert]. Ridgefield, CT: Boehringer Ingelheim 2018."},{"key":"1052_CR38","unstructured":"WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. Geneva: World Health Organization. 2000."}],"updated-by":[{"DOI":"10.1007\/s12325-019-01082-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000}}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-019-01052-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12325-019-01052-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-019-01052-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T23:08:17Z","timestamp":1596928097000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12325-019-01052-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,10]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["1052"],"URL":"https:\/\/doi.org\/10.1007\/s12325-019-01052-y","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s12325-019-01082-6","asserted-by":"object"}]},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,10]]},"assertion":[{"value":"25 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2019","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2019","order":3,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":4,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the Original Publication the colors of Figure\u00a02 have been switched. The correct figures are given below.","order":5,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}}]}}