RESUMO
BACKGROUND: In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS: Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS: In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166997.
Assuntos
Heparina/uso terapêutico , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Ultrassonografia de Intervenção , Dispositivos de Acesso Vascular , Doença Aguda , Idoso , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Hemorragia/epidemiologia , Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: The ETHOS I trial was the first in-human experience evaluating the safety and efficacy of two different release formulations of the 17-beta estradiol-eluting R-Stent versus uncoated control stents for the treatment of patients with single de novo native coronary lesions. BACKGROUND: Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in-stent restenosis. METHODS: Ninety-five patients were randomized to receive a slow-release (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6-month percent in-stent volume obstruction by intravascular ultrasound (IVUS). RESULTS: Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% +/- 14%, 33% +/- 11%, and 31% +/- 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 +/- 0.49 mm, 0.86 +/- 0.53 mm, and 0.84 +/- 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31). CONCLUSIONS: In this first-in-man randomized trial, the 17-beta estradiol-eluting R-Stent, in either slow- or moderate-release formulations, was well-tolerated, but showed no benefit for treatment of coronary lesions when compared to controls.
Assuntos
Estenose Coronária/terapia , Estradiol/administração & dosagem , Stents , Análise de Variância , Brasil , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/patologia , Reestenose Coronária/prevenção & controle , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/patologia , Método Duplo-Cego , Sistemas de Liberação de Medicamentos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Polímeros , Estudos Prospectivos , Resultado do TratamentoRESUMO
Objectives: The ETHOS I trial was the first in-human experience evaluating the safety and efficacy of two different release formulations of the 17-b estradiol-eluting RStent TM versus uncoated control stents for the treatment of patients with single de novo native coronary lesions. Background: Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in-stent restenosis. Methods: Ninety-five patients were randomized to receive a slowrelease (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6-month percent in-stent volume obstruction by intravascular ultrasound (IVUS). Results: Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% 6 14%, 33% 6 11%, and 31% 6 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 6 0.49 mm, 0.86 6 0.53 mm, and 0.84 6 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31). Conclusions: In this first-in-man randomized trial, the 17-b estradiol-eluting R-StentTM, in either slowor moderate-release formulations, was well-tolerated, but showed no benefit for treatment of coronary lesions when compared to controls.
Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , StentsRESUMO
Objectives: The ETHOS I trial was the first in-human experience evaluating the safety
and efficacy of two different release formulations of the 17-b estradiol-eluting RStent
TM versus uncoated control stents for the treatment of patients with single de
novo native coronary lesions. Background: Estrogens were reported to inhibit neointimal
proliferation and to accelerate endothelial regeneration after coronary angioplasty
and thus could be an ideal compound to deliver on a stent for the purpose of reducing
in-stent restenosis. Methods: Ninety-five patients were randomized to receive a slowrelease
(n = 32) or the moderate release (n = 31) formulations or the bare metal stent
(n = 32). The primary end point was the 6-month percent in-stent volume obstruction
by intravascular ultrasound (IVUS). Results: Diabetes was present in 29.5% of patients;
the mean reference vessel diameter was 2.90 mm; and the mean lesion length was
13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did
not differ significantly between the 3 groups (31% 6 14%, 33% 6 11%, and 31% 6
14%, P = 0.83). Secondary endpoints also did not differ significantly between the
groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%,
14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 6 0.49 mm, 0.86 6 0.53 mm, and
0.84 6 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P =
0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31). Conclusions:
In this first-in-man randomized trial, the 17-b estradiol-eluting R-StentTM, in either slowor
moderate-release formulations, was well-tolerated, but showed no benefit for treatment
of coronary lesions when compared to controls.