BACKGROUND: Primary percutaneous coronary intervention (PCI) is more effective than fibrinolytic therapy for ST-segment elevation acute myocardial infarction (STEMI), but time to intervention can be considerable. Our aim was to investigate whether the administration of full-dose tenecteplase before a delayed PCI could mitigate the negative effect of this delay.
METHODS: We did a randomised study in which we assigned patients with STEMI of less than 6 h duration (scheduled to undergo primary PCI with an anticipated delay of 1-3 h) to standard PCI (n=838) or PCI preceded by administration of full-dose tenecteplase (n=829). All patients received aspirin and a bolus, without an infusion, of unfractionated heparin. Our primary endpoint was death or congestive heart failure or shock within 90 days. Analyses were by intention to treat. This study is registered with , number NCT00168792.
FINDINGS: We planned to enroll 4000 patients, but early cessation of enrollment was recommended by the data and safety monitoring board because of a higher in-hospital mortality in the facilitated than in the standard PCI group (6% [43 of 664] vs 3% [22 of 656], p=0.0105). Of those enrolled, six were lost to follow-up in the facilitated PCI group and seven in the other group. Median time from randomisation to first balloon inflation was similar in both groups. The median time from bolus tenecteplase to first balloon inflation was 104 min. We noted the primary endpoint in 19% (151 of 810) of patients assigned facilitated PCI versus 13% (110 of 819) of those randomised to primary PCI (relative risk 1.39, 95% CI 1.11-1.74; p=0.0045). During hospital stay, significantly more strokes (1.8% [15 of 829] vs 0, p<0.0001), but not major non-cerebral bleeding complications (6% [46 of 829] vs 4% [37 of 838], p=0.3118), were reported in patients assigned facilitated rather than standard PCI. We also noted more ischaemic cardiac complications, such as reinfarction (6% [49 of 805] vs 4% [30 of 820], p=0.0279) or repeat target vessel revascularisation (7% [53 of 805] vs 3% [28 of 818], p=0.0041) within 90 days in this study group.
INTERPRETATION: A strategy of full-dose tenecteplase with antithrombotic co-therapy, as used in this study and preceding PCI by 1-3 h, was associated with more major adverse events than PCI alone in STEMI and cannot be recommended.
OBJETIVOS: Se comparó una estrategia de tenecteplasa (TNK)-angioplastia facilitada con uno de TNK solo en pacientes con alto riesgo de elevación del segmento ST del infarto de miocardio (STEMI). Antecedentes: Estudios previos muestran que la trombolisis seguida de angioplastia inmediata para el tratamiento del IAMEST no mejora los resultados isquémicos en comparación con la trombólisis solo y se asocia con complicaciones de sangrado excesivo. Desde la publicación de estos ensayos, sin embargo, importantes avances farmacológicos y tecnológicos se han producido. MÉTODOS: Se azar 170 pacientes con alto riesgo STEMI al tratamiento con TNK sola (84 pacientes) o TNK-angioplastia facilitada (86 pacientes). El punto final primario fue un compuesto de muerte, reinfarto, isquemia inestable recurrente o ictus a los seis meses. RESULTADOS: A los seis meses, la incidencia del punto final primario fue del 24,4% en el grupo TNK-sola frente a un 11,6% en el grupo TNK-angioplastia facilitada (p = 0,04). Esta diferencia fue impulsado por una reducción en la tasa de isquemia inestable recurrente (20,7% frente a 8,1%, p = 0,03). Hubo una tendencia hacia una tasa de reinfarto inferior con TNK-angioplastia facilitada (14,6% vs 5,8%, p = 0,07). No se observaron diferencias significativas en las tasas de muerte o accidente cerebrovascular. Se observó hemorragia grave en el 7,1% del grupo TNK-solo y en el 8,1% de la TNK-grupo de angioplastia facilitada (p = 1,00). CONCLUSIONES: En pacientes con alto riesgo STEMI, TNK y sometidos a angioplastia inmediata redujo el riesgo de eventos isquémicos recurrentes en comparación con TNK solo y no se asoció con un aumento de complicaciones hemorrágicas graves.
ANTECEDENTES: El tratamiento adecuado para pacientes en los que la reperfusión no se produce después del tratamiento trombolítico para el infarto de miocardio agudo sigue siendo poco clara. Hay pocos datos que comparan una intervención coronaria percutánea (ICP de rescate) de emergencia con el tratamiento conservador en estos pacientes, y ninguno que comparan ICP de rescate con trombólisis repetida.
MÉTODOS: Se realizó un estudio multicéntrico en el Reino Unido que involucra 427 pacientes con elevación del segmento ST infarto de miocardio en los que la reperfusión no ocurrió (menos del 50 por ciento de resolución del segmento ST) dentro de los 90 minutos después del tratamiento trombolítico. Los pacientes fueron asignados al azar a la trombólisis repetida (142 pacientes), el tratamiento conservador (141 pacientes), o ICP de rescate (144 pacientes). El punto final primario fue un compuesto de muerte, reinfarto, accidente cerebrovascular o insuficiencia cardiaca grave dentro de los seis meses.
RESULTADOS: La tasa de supervivencia libre de eventos entre los pacientes tratados con ICP de rescate fue del 84,6 por ciento, en comparación con el 70,1 por ciento entre los que recibieron tratamiento conservador y el 68,7 por ciento entre los sometidos a trombólisis repetida (P total = 0,004). La razón de riesgo ajustada para la ocurrencia de la variable principal para la trombólisis repetida versus tratamiento conservador fue de 1,09 (intervalo de confianza del 95 por ciento, 0,71 a 1,67; P = 0,69), en comparación con las proporciones de riesgo ajustado de intervalo de confianza de 0,43 (95 por ciento, 0,26 a 0,72; P = 0,001) para la ICP de rescate frente a la trombólisis repetida y 0,47 (intervalo de confianza del 95 por ciento, 0,28-0,79; p = 0,004) para la ICP de rescate versus tratamiento conservador. No hubo diferencias significativas en la mortalidad por todas las causas. El sangrado no fatal, sobre todo en el sitio de la vaina-inserción, fue más frecuente con ICP de rescate. A los seis meses, el 86,2 por ciento del grupo de rescate en PCI libres de la revascularización, en comparación con el 77,6 por ciento del grupo de tratamiento conservador y el 74,4 por ciento del grupo-trombólisis repetida (global P = 0,05).
CONCLUSIONES: La supervivencia sin después del tratamiento trombolítico no fue significativamente mayor con la ICP de rescate que con trombólisis repetida o tratamiento conservador. ICP de rescate debe ser considerada para pacientes en los que la reperfusión no se produce después de la terapia trombolítica.
OBJECTIVE: To report one year results of the MERLIN (Middlesbrough early revascularisation to limit infarction) trial, a prospective randomised trial comparing the strategy of coronary angiography and urgent revascularisation with conservative treatment in patients with failed fibrinolysis complicating ST segment elevation myocardial infarction (STEMI). The 30 day results have recently been published. At the planning stage of the trial, it was determined that follow up of trial patients would continue annually to three years to determine whether late benefit occurred.
SUBJECTS: 307 patients who received a fibrinolytic for STEMI but failed to reperfuse early according to previously described ECG criteria and did not develop cardiogenic shock.
METHODS: Patients were randomly assigned to receive either emergency coronary angiography with a view to proceeding to urgent revascularisation (rescue percutaneous coronary intervention (rPCI) arm) or continued medical treatment (conservative arm). The primary end point was all cause mortality at 30 days. The secondary end points included the composite end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure at 30 days. The same end points were evaluated at one year and these results are presented.
RESULTS: All cause mortality at one year was similar in the conservative arm and the rPCI arm (13.0% v 14.4%, p = 0.7, risk difference (RD) -1.4%, 95% confidence interval (CI) -9.3 to 6.4). The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure was significantly higher in the conservative arm (57.8% v 43.1%, p = 0.01, RD 14.7%, 95% CI 3.5% to 25.5%). This was driven almost exclusively by a significantly higher incidence of subsequent unplanned revascularisation in the conservative arm (29.9% v 12.4%, p < 0.001, RD 17.5%, 95% CI 8.5% to 26.4%). Reinfarction and clinical heart failure were numerically, but not statistically, more common in the conservative arm (14.3% v 10.5%, p = 0.3, RD 3.8%, 95% CI -3.7 to 11.4, and 31.2% v 26.1%, p = 0.3, RD 5.0%, 95% CI -5.1 to 15.1). There was a strong trend towards fewer strokes in the conservative arm (1.3% v 5.2%, p = 0.06, RD -3.9%, 95% CI -8.9 to 0.06).
CONCLUSION: At one year of follow up, there was no survival advantage in the rPCI arm compared with the conservative arm. The incidence of the composite secondary end point was significantly lower in the rPCI arm, but this was driven almost entirely by a highly significant reduction in the incidence of further revascularisation.
OBJECTIVES: We sought to compare emergency coronary angiography with or without rescue percutaneous coronary intervention (PCI) with conservative treatment in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction (STEMI).
BACKGROUND: Most patients with STEMI receive fibrinolytic therapy and aspirin. The management of failed fibrinolysis is unclear.
METHODS: A total of 307 patients with STEMI and failed fibrinolysis were randomized to emergency coronary angiography with or without rescue PCI or conservative treatment.
RESULTS: Thirty-day all-cause mortality was similar in the rescue and conservative groups (9.8% vs. 11%, p = 0.7, risk difference [RD] 1.2%, 95% confidence interval [CI] -5.8 to 8.3). The composite secondary end point of death/re-infarction/stroke/subsequent revascularization/heart failure occurred less frequently in the rescue group (37.3% vs. 50%, p = 0.02, RD 12.7%, 95% CI 1.6 to 23.5), driven by less subsequent revascularization (6.5% vs. 20.1%, p < 0.01, RD 13.6%, 95% CI 6.2 to 21.4). Re-infarction and clinical heart failure were less common in the rescue group (7.2% vs. 10.4%, p = 0.3, RD 3.2%, 95% CI -3.3 to 9.9; and 24.2% vs. 29.2%, p = 0.3, RD 5.7%, 95% CI -4.3 to 15.6, respectively). Strokes and transfusions were more common in the rescue group (4.6% vs. 0.6%, p = 0.03, RD 3.9%, 95% CI 0.5 to 8.6; and 11.1% vs. 1.3%, p < 0.001, RD 9.8%, 95% CI 4.9 to 19.9, respectively). Left ventricular function at 30 days was the same in the two groups.
CONCLUSIONS: Rescue angioplasty did not improve survival by 30 days, but improved event-free survival, almost completely due to a reduction in subsequent revascularization. Rescue angioplasty was associated with more strokes and more transfusions and did not result in preservation of left ventricular systolic function at 30 days.
BACKGROUND: Percutaneous coronary intervention (PCI) has emerged as the strategy of choice in reestablishing effective flow in occluded infarct-related arteries in patients with acute myocardial infarction (MI) if it can be administered in a timely fashion. Patients who enter the catheterization laboratory with Thrombolysis In Myocardial Infarction (TIMI) grade 3 blood flow in the infarct-related vessel have better clinical outcomes than patients presenting with impaired flow. We hypothesize that a strategy of early pharmacologic reperfusion therapy with abciximab alone or in conjunction with reduced-dose reteplase, followed by PCI will improve the outcome of patients eligible for primary PCI.
STUDY DESIGN: The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) study is a 3000-patient, prospective, multicenter, randomized, double-blind, placebo-controlled trial. The study is designed to compare the efficacy and safety of early administration of reduced-dose reteplase and abciximab combination therapy or abciximab alone followed by PCI with abciximab alone administered just before PCI for acute MI. Patients will be randomized to one of these 2 facilitated PCI treatments or primary PCI in a 1:1:1 fashion. The primary efficacy end point of FINESSE is the composite of all-cause mortality or post-MI complications within 90 days of randomization. The primary safety outcome assessment will be Thrombolysis In Myocardial Infarction (TIMI) major bleeding.
CONCLUSIONS: The FINESSE study will answer important questions regarding the efficacy and safety of "upstream" medical therapy followed by planned intervention for patients with ST-elevation MI, potentially expanding the population eligible for a primary PCI approach. This study will also provide insight as to which facilitated regimen (reteplase/abciximab combination therapy or abciximab monotherapy) provides the best balance of efficacy and safety.
ANTECEDENTES: En los pacientes con elevación del segmento ST del infarto de miocardio (STEMI), inmediatamente posterior a la trombolisis rutina de la angioplastia ha sido desalentado por su asociación con la alta incidencia de eventos. El estudio GRACIA-1 ensayo fue diseñado para evaluar de nuevo los beneficios de uno de los primeros post-trombolisis enfoque de intervención en la era de los stents y los nuevos agentes antiplaquetarios. Métodos: 500 pacientes con STEMI thrombolysed (con activador tisular del plasminógeno recombinante) fueron asignados al azar a la angiografía y la intervención si así se indica en las 24 horas de la trombolisis, o un enfoque guiado por isquemia conservador. El objetivo primario fue la tasa combinada de muerte, reinfarto o revascularización a los 12 meses. El análisis fue por intención de tratar. RESULTADOS: El tratamiento invasivo incluyó implante de stent en la arteria responsable en el 80% (199 de 248) de los pacientes, la cirugía de bypass en seis (2%), no culpable de la arteria con stent en tres, y ninguna intervención en el 40 (16%). Revascularización previa al que se necesitaba en 51 de 252 pacientes en el grupo conservador. En comparación con los pacientes que recibieron tratamiento conservador, por un año, los pacientes en el grupo invasivo tuvieron menor frecuencia de la variable principal de valoración (23 [9%] frente a 51 [21%], cociente de riesgo 0,44 [IC 95% 0,28-0,70], p = 0,0008), y que tendían a tener una tasa de reducción de muerte o reinfarto (7% vs 12%, 0,59 [0,33-1,05], p = 0,07). Índice de tiempo en el hospital fue más corta en el grupo invasivo, sin diferencias en el sangrado mayor o complicaciones vasculares. A los 30 días ambos grupos tuvieron una incidencia similar de eventos cardíacos. En el hospital la incidencia de revascularización inducida por la recurrencia espontánea de isquemia fue mayor en los pacientes en el grupo conservador que en los del grupo invasor. En conclusión, en pacientes con STEMI, el cateterismo precoz post-trombolisis y la intervención apropiada es seguro y puede ser preferible a una estrategia conservadora, ya que reduce la necesidad de no planificado en el hospital de revascularización, y la mejora de 1 año el resultado clínico.
OBJECTIVE: We investigated the acute-phrase and chronic-phase outcomes of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with or without antecedent mutant tissue-type plasminogen (t-PA) administration.
METHODS: Thirty-nine patients with a first AMI within 6 hours of onset were randomly assigned to the treatment group (1,600,000 IU IV monteplase, n = 19) or the nontreatment group (n = 20), followed by PCI. Clinical outcomes were then evaluated.
RESULTS: Patient characteristics did not differ between the 2 groups. A significantly higher number of patients in the monteplase group achieved Thrombolysis In Myocardial Infarction trial (TIMI) grade 2 flow or more at the first angiography (84.2% vs 40.0%; P <.005), reduced number of devices (1.44 vs 1.80 devices, P <.05), and reduced procedure times (59.7 vs 86.7 minutes; P <.01), with no differences in peak creatine kinase and rates of major complications and no reflow or distal embolization. Observation over an average of 5.5 months revealed a tendency toward lower target lesion revascularization rates in the monteplase group (17.6% vs 31.6%) but no intergroup difference in rates of major complications. Pretreatment quantitative coronary angioplasty only showed a significant difference in minimal lumen diameter and percent diameter stenosis in the acute phase (1.13 mm in the monteplase group vs 0.66 mm in the nontreatment group, 57.0% vs 73.0%; P <.05). (99m)Tc-QGS (quantitative electrocardiographically gated single-photon emission computed tomographic scintigraphy) showed no intergroup differences in left ventricular end-diastolic volume index, end- systolic volume index, and ejection fraction in the acute and chronic phases.
CONCLUSIONS: Our results suggest that PCI with antecedent mutant t-PA for AMI not only accelerates reperfusion, thereby facilitating PCI, but also attenuates restenosis in the chronic phase.
CONTEXT: The optimal pharmacological strategy for bridging the delay between admission and performance of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) is not known.
OBJECTIVE: To assess whether early administration of reteplase plus abciximab produces better results compared with abciximab alone in patients with acute MI referred for PCI.
DESIGN, SETTING, AND PATIENTS: Open-label, randomized controlled study conducted from May 3, 2001, through June 2, 2003, of 253 patients who were admitted to 13 community hospitals without catheterization facilities (n = 186) and to 5 hospitals with catheterization facilities (n = 67), with the diagnosis of an ST-segment elevation acute MI within 12 hours from onset of symptoms.
INTERVENTIONS: Patients received intravenously either the combination of a half-dose reteplase (two 5-U boluses, 30 minutes apart) with a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 microg/min for 12 hours]) or the standard dose of abciximab alone; all patients were then transferred for PCI.
MAIN OUTCOME MEASURE: Final infarct size according to a single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 228 patients (90.1% of entire sample).
RESULTS: Of the 253 patients enrolled, 125 were assigned to reteplase plus abciximab and 128 to abciximab alone. The median (interquartile range) of the final infarct size of the left ventricle was 13.0% (3.0%-28.0%) in the reteplase plus abciximab group and 11.5% (3.0%-26.3%) in the abciximab-alone group (P =.81). The mean difference in final infarct size of left ventricle between the reteplase plus abciximab group and the abciximab group was 1.3% (95% confidence interval [CI], -3.1% to 5.7%). Within 6 months after randomization, the composite secondary end point of death, recurrent MI, or stroke occurred in 8 patients (6.4%) in the reteplase plus abciximab group and 6 patients (4.7%) in the abciximab group (relative risk, 1.4; 95% CI, 0.5-3.9; log-rank P =.56). Major bleeding complications were observed in 7 patients (5.6%) in the reteplase plus abciximab group and 2 patients (1.6%) in the abciximab group (P =.16).
CONCLUSION: Early administration of reteplase plus abciximab does not lead to a reduction of infarct size compared with abciximab alone in patients with acute MI referred for PCI.
