Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study.
Circulation
; 127(10): 1128-38, 2013 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-23403476
ABSTRACT
BACKGROUND:
By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH). METHODS ANDRESULTS:
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 ≥ 800 dyne·s·cm(-5) symptomatic on ≥ 2 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, 12-52; P=0.002), an effect maintained in the extension study in patients remaining on imatinib. Pulmonary vascular resistance decreased by 379 dyne·s·cm(-5) (95% confidence interval, -502 to - 255; P<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.CONCLUSIONS:
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. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT00902174 (core study); NCT01392495 (extension).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Pirimidinas
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Hipertensão Pulmonar
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Circulation
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha