{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:08:02Z","timestamp":1791896882116,"version":"4.3.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,3,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study (IMPRES), a randomized, double-blind, placebo-controlled 24-week trial, evaluated imatinib in patients with pulmonary vascular resistance \u2265800 dyne\u00b7s\u00b7cm\n                      <jats:sup>\u22125<\/jats:sup>\n                      symptomatic on \u22652 PAH therapies. The primary outcome was change in 6-minute walk distance. Secondary outcomes included changes in hemodynamics, functional class, serum levels of N-terminal brain natriuretic peptide, and time to clinical worsening. After completion of the core study, patients could enter an open-label long-term extension study. Of 202 patients enrolled, 41% patients received 3 PAH therapies, with the remainder on 2 therapies. After 24 weeks, the mean placebo-corrected treatment effect on 6-minute walk distance was 32 m (95% confidence interval, 12\u201352;\n                      <jats:italic>P<\/jats:italic>\n                      =0.002), an effect maintained in the extension study in patients remaining on imatinib. Pulmonary vascular resistance decreased by 379 dyne\u00b7s\u00b7cm\n                      <jats:sup>\u22125<\/jats:sup>\n                      (95% confidence interval, \u2212502 to \u2212 255;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001, between-group difference). Functional class, time to clinical worsening, and mortality did not differ between treatments. Serious adverse events and discontinuations were more frequent with imatinib than placebo (44% versus 30% and 33% versus 18%, respectively). Subdural hematoma occurred in 8 patients (2 in the core study, 6 in the extension) receiving imatinib and anticoagulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Imatinib improved exercise capacity and hemodynamics in patients with advanced PAH, but serious adverse events and study drug discontinuations were common. Further studies are needed to investigate the long-term safety and efficacy of imatinib in patients with PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT00902174 (core study); NCT01392495 (extension).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.112.000765","type":"journal-article","created":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T00:05:13Z","timestamp":1360713913000},"page":"1128-1138","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":549,"title":["Imatinib Mesylate as Add-on Therapy for Pulmonary Arterial Hypertension"],"prefix":"10.1161","volume":"127","author":[{"given":"Marius M.","family":"Hoeper","sequence":"first","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn J.","family":"Barst","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Bourge","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Feldman","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adaani E.","family":"Frost","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazzareno","family":"Gali\u00e9","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"G\u00f3mez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Grimminger","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Gr\u00fcnig","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); 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Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); Johns..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Peacock","sequence":"additional","affiliation":[{"name":"From Medizinische Hochschule, Hannover, Germany (M.M.H.); Columbia University, New York, NY (R.J.B.); University of Alabama at Birmingham (R.C.B.); Arizona Pulmonary Specialists, Phoenix (J.F.); Baylor College of Medicine, Houston, TX (A.E.F.); Universit\u00e0 di Bologna, Bologna, Italy (N.G.); Hospital Universitario Doce de Octubre, Madrid, Spain (M.A.G.-S.); University Hospital Giessen and Marburg GmbH, Giessen, Germany (F.G., H.G.); University Hospital Heidelberg, Heidelberg, Germany (E.G.); 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