Academic Journal
Long-term safety and efficacy of imatinib in pulmonary arterial hypertension
| العنوان: | Long-term safety and efficacy of imatinib in pulmonary arterial hypertension |
|---|---|
| المساهمون: | College of Medicine, Dept. of Internal Medicine, Adaani E.Frost, Robyn J.Barst, Marius M.Hoeper, Hyuk-Jae Chang, Robert P.Frantz, Yoshihiro Fukumoto, Nazzareno Gali챕, Paul M.Hassoun, Hans Klose, Hiromi Matsubara, Nicholas W.Morrell, Andrew J.Peacock, Michael Pfeifer, G챕rald Simonneau, Victor F.Tapson, Fernando Torres, Carmine Dario Vizza, David Lawrence, Wei Yang, James M.Felser, Deborah A.Quinn, Hossein-Ardeschir Ghofrani, Chang, Hyuck Jae |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adolescent, Adult, Aged, Dose-Response Relationship, Drug, Double-Blind Method, Exercise Tolerance/physiology, Female, Follow-Up Studies, Hemodynamics/drug effects, Humans, Hypertension, Pulmonary/drug therapy, Pulmonary/physiopathology, Imatinib Mesylate/administration & dosage, Male, Middle Aged, Protein Kinase Inhibitors/administration & dosage, Retrospective Studies, Time Factors, Treatment Outcome, Young Adult, efficacy, imatinib, long-term, pulmonary arterial hypertension, safety |
| الوصف: | BACKGROUND: Imatinib is an oral inhibitor of several protein kinases implicated in the pathophysiology of pulmonary hypertension. Treatment with imatinib resulted in improved hemodynamics and exercise capacity in a controlled trial (Imatinib [QTI571] in Pulmonary Arterial Hypertension, a Randomized Efficacy Study [IMPRES]), among pulmonary arterial hypertension (PAH) patients inadequately responsive to 2 to 3 PAH-specific therapies. METHODS: The long-term (up to 204 weeks) safety and efficacy of imatinib in this open-label extension study were reviewed until early study termination on April 16, 2014. Of 202 IMPRES-enrolled patients, 66 imatinib and 78 placebo recipients entered the extension. RESULTS: Overall, 93.8% (135 of 144) of patients discontinued the extension study; administrative issues (i.e., sponsor termination; 32.6%) and adverse events (31.3%) were the primary reasons for discontinuation. Nine patients completed the extension study before it was terminated. Serious and unexpected adverse events were frequent. These included 6 subdural hematomas in the extension study and 17 deaths during or within 30 days of study end. Although the patients who tolerated imatinib and remained in the extension for a longer duration did experience an improvement in functional class and walk distance, most discontinued the drug and the study. CONCLUSIONS: Severe adverse events, significant side effects, and a high discontinuation rate limit the utility of imatinib in the treatment of PAH. These risks outweigh any possible improvements in hemodynamics and walk distance seen in those patients able to remain on drug. The off-label use of this compound in PAH is discouraged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01392495. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1053-2498 1557-3117 |
| Relation: | JOURNAL OF HEART AND LUNG TRANSPLANTATION; J01436; OAK-2015-07414; https://ir.ymlib.yonsei.ac.kr/handle/22282913/157294; T201506163; JOURNAL OF HEART AND LUNG TRANSPLANTATION, Vol.34(11) : 1366-1375, 2015 |
| DOI: | 10.1016/j.healun.2015.05.025 |
| الاتاحة: | https://ir.ymlib.yonsei.ac.kr/handle/22282913/157294 https://doi.org/10.1016/j.healun.2015.05.025 |
| Rights: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ |
| رقم الانضمام: | edsbas.788931DF |
| قاعدة البيانات: | BASE |
| تدمد: | 10532498 15573117 |
|---|---|
| DOI: | 10.1016/j.healun.2015.05.025 |