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

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 off-label with imatinib 400 mg daily. Pulmonary hypertension-specific 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-year survival 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 patient-years is concerning. However, adjusting the INR to around 2.0 might obviate this complication.

• Authors: Rudolf Speich, Silvia Ulrich, Guido Domenighetti, Lars C Huber, Manuel Fischler, Ursula Treder, Alexander Breitenstein
• Journal: Respiration; international review of thoracic diseases (Respiration) Vol. 89 Issue 6 Pg. 515-24 ( 2015) ISSN: 1423-0356 [Electronic] Switzerland
• PMID: 26043786 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Protein Kinase Inhibitors
• Imatinib Mesylate

Topics

• Adult
• Aged
• Echocardiography
• Female
• Hematoma, Subdural (chemically induced)
• Hemodynamics
• Humans
• Hypertension, Pulmonary (diagnostic imaging, drug therapy)
• Imatinib Mesylate (therapeutic use)
• International Normalized Ratio
• Longitudinal Studies
• Male
• Middle Aged
• Protein Kinase Inhibitors (therapeutic use)
• Quality of Life
• Remission Induction
• Severity of Illness Index
• Treatment Outcome
• Young Adult