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Efficacy and Safety of Long-Term Imatinib Therapy for Pulmonary Arterial Hypertension


Speich, Rudolf; Ulrich, Silvia; Domenighetti, Guido; Huber, Lars C; Fischler, Manuel; Treder, Ursula; Breitenstein, Alexander (2015). Efficacy and Safety of Long-Term Imatinib Therapy for Pulmonary Arterial Hypertension. Respiration, 89(6):515-524.

Abstract

Background: Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH). Objective: To evaluate the long-term efficacy and safety of imatinib. Methods: This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated offlabel with imatinib 400 mg daily. Pulmonary hypertensionspecific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients). Results: After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of ‘hemodynamic remission’. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-yearsurvival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years. Conclusions: Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patientyears is concerning. However, adjusting the INR to around 2.0 might obviate this complication.

Abstract

Background: Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH). Objective: To evaluate the long-term efficacy and safety of imatinib. Methods: This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated offlabel with imatinib 400 mg daily. Pulmonary hypertensionspecific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients). Results: After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of ‘hemodynamic remission’. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-yearsurvival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years. Conclusions: Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patientyears is concerning. However, adjusting the INR to around 2.0 might obviate this complication.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:26 Nov 2015 12:56
Last Modified:01 Aug 2016 00:00
Publisher:Karger
ISSN:0025-7931
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000381923
PubMed ID:26043786

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