{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:14:20Z","timestamp":1787318060502,"version":"build-2736575974"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,3,31]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>BCR-ABL (fusion between the Abelson [Abl] tyrosine kinase gene at chromosome 9 and the break point cluster [Bcr] gene at chromosome 22) tyrosine kinase inhibitors (TKIs) have been increasingly linked to pulmonary arterial hypertension (PAH) since 2009, although supporting evidence is limited. Our objective was to evaluate the risk of PAH associated with second- and third-generation BCR-ABL TKIs compared with imatinib in adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We employed a prevalent new-user design that emulates a randomized trial within the French national health care database population between 2008 and 2024. Thus, subjects initiating a second- and third-generation BCR-ABL TKI were matched on time and propensity score with users of the first-generation BCR-ABL TKI, imatinib. Patients were followed to occurrence of the primary outcome (ie, new onset of PAH), switch to another BCR-ABL TKI, death from any cause, end of registration within the database, or end of the study period, whichever came first. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models, and incidence rates and corresponding 95% CIs were calculated using the Poisson distribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Six thousand six hundred twenty-five dasatinib (age 59.7\u00b115.2 years, 44.0% women), 5205 nilotinib (age 55.4\u00b115.0 years, 44.2% women), 2421 bosutinib (age 63.8\u00b114.2 years, 42.1% women),1358 ponatinib (age 57.3\u00b114.9 years, 46.1% women), and 922 asciminib (age 64.3\u00b113.8 years, 43.7% female) new users were each matched with the maximum of available imatinib users on time-conditional propensity score and on duration of prior imatinib use (prevalent users). Dasatinib use was associated with a 9-fold increased risk of PAH compared with imatinib (1829 versus 43 events per million persons per year; HR=8.89 [95% CI, 5.30\u201314.92]). Bosutinib and ponatinib were associated with HRs of 10.76 (95% CI, 4.68\u201324.73) and 7.74 (95% CI, 2.33\u201325.70) respectively, with most cases occurring in patients previously exposed to dasatinib. Nilotinib and asciminib were not associated with an increased risk of PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This study, designed to emulate a randomized trial, suggests that, in French patients with chronic myeloid leukemia treated with BCR-ABL TKIs, dasatinib use is associated with a higher risk of PAH compared with imatinib, while bosutinib and ponatinib exposure may aggravate or trigger a recurrence of PAH in patients with preexisting dasatinib exposure. Whether bosutinib and ponatinib could induce PAH without preexposure to dasatinib remains to be explored.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.077764","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:00:26Z","timestamp":1770890426000},"page":"967-979","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Second- and Third-Generation BCR-ABL Tyrosine Kinase Inhibitors and the Risk of Pulmonary Arterial Hypertension: A Prevalent New-User Design"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6619-4130","authenticated-orcid":true,"given":"Cl\u00e9ment","family":"Jambon-Barbara","sequence":"first","affiliation":[{"name":"Pharmacovigilance Department (C.J.-B., A.H., J.-L.C., C.K.), Grenoble Alpes University Hospital, Grenoble, France."},{"name":"HP2 Laboratory, INSERM U1300, Universit\u00e9 Grenoble Alpes, Grenoble, France (C.J.-B., A.H., J.-L.C., C.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1281-5296","authenticated-orcid":true,"given":"Samy","family":"Suissa","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada (S.S., S.D.)."},{"name":"Departments of Epidemiology, Biostatistics and Occupational Health and Medicine, McGill University, Montreal, QC, Canada (S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-7876","authenticated-orcid":true,"given":"Sophie","family":"Dell\u2019Aniello","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada (S.S., S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8483-5023","authenticated-orcid":true,"given":"Alex","family":"Hlavaty","sequence":"additional","affiliation":[{"name":"Pharmacovigilance Department (C.J.-B., A.H., J.-L.C., C.K.), Grenoble Alpes University Hospital, Grenoble, France."},{"name":"HP2 Laboratory, INSERM U1300, Universit\u00e9 Grenoble Alpes, Grenoble, France (C.J.-B., A.H., J.-L.C., C.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-1469","authenticated-orcid":true,"given":"Jean-Luc","family":"Cracowski","sequence":"additional","affiliation":[{"name":"Pharmacovigilance Department (C.J.-B., A.H., J.-L.C., C.K.), Grenoble Alpes University Hospital, Grenoble, France."},{"name":"HP2 Laboratory, INSERM U1300, Universit\u00e9 Grenoble Alpes, Grenoble, France (C.J.-B., A.H., J.-L.C., C.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-8442","authenticated-orcid":true,"given":"Marie-Camille","family":"Chaumais","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (M.-C.C., M.H., D.M.)."},{"name":"Departments of Pharmacy (M.-C.C.), Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Bic\u00eatre, Le Kremlin-Bic\u00eatre, France."},{"name":"Faculty of Pharmacy, Universit\u00e9 Paris-Saclay, Saclay, France (M.-C.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-2892","authenticated-orcid":true,"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (M.-C.C., M.H., D.M.)."},{"name":"Respiratory and Intensive Care Medicine (M.H., D.M.), Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Bic\u00eatre, Le Kremlin-Bic\u00eatre, France."},{"name":"Faculty of Medicine, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France (M.H., D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-6922","authenticated-orcid":true,"given":"David","family":"Montani","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (M.-C.C., M.H., D.M.)."},{"name":"Respiratory and Intensive Care Medicine (M.H., D.M.), Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Bic\u00eatre, Le Kremlin-Bic\u00eatre, France."},{"name":"Faculty of Medicine, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France (M.H., D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-8573","authenticated-orcid":true,"given":"Charles","family":"Khouri","sequence":"additional","affiliation":[{"name":"Pharmacovigilance Department (C.J.-B., A.H., J.-L.C., C.K.), Grenoble Alpes University Hospital, Grenoble, France."},{"name":"Clinical Pharmacology Department, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Centre d'Investigation Clinique 1406 (C.K.), Grenoble Alpes University Hospital, Grenoble, France."},{"name":"HP2 Laboratory, INSERM U1300, Universit\u00e9 Grenoble Alpes, Grenoble, France (C.J.-B., A.H., J.-L.C., C.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01324-2024"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5492"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1140"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200510-1668OC"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-019-06920-x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01913-2018"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2008.415"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2008.09.026"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01110-2015"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01004-2016"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-012-1103-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02472-2018"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000765"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86249"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0332OC"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2023-0185OC"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01634-2023"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39335.541782.AD"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k3532"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4107"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001628"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4233"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.respe.2017.05.004"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.therap.2023.01.009"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2302134"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2023.2900"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-078078"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00217-2017"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6593"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/03610910902859574"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198806303182605"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0903274"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00109-2024"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.0220"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202411-2339pp"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00279-2020"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000412"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.079921"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2019.08.002"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15436"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/15563650.2018.1447119"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01004-2016"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01410-2016"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1177\/2045893217733444"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lrr.2022.100312"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0000000000001156"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00943-2024"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1177\/2045894020936913"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2022.12.016"},{"key":"e_1_3_3_53_2","unstructured":"Initiation of DARWIN EU\u00ae Coordination Centre advances integration real-world evidence into assessment medicines in the EU. European Medicines Agency. Accessed December 23 2025. https:\/\/www.ema.europa.eu\/en\/news\/initiation-darwin-eur-coordination-centre-advances-integration-real-world-evidence-assessment"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5587"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.30"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5083"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaa164"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.125.077764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:44:06Z","timestamp":1785854646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.125.077764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":56,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,3,31]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.125.077764"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.125.077764","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"2025-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}