Angioplastia Facilitada Andres Fernandez Cadavid Clinica Cardiovascular Santa Maria

OPCIONES TRATAMIENTO EN INFARTO AGUDO DEL MIOCARDIO CON ELEVACION DEL SEGMENTO ST TROMBOLISIS INTERVENCION CORONARIA PERCUTANEA TERAPIA COMBINADA Tromboliticos + Intervencion coronaria percutánea Inhibidor de glicoproteína IIB IIIA + Intervención percutánea Tromboliticos + Inhibidor de glicoproteína IIB IIIA + Intervención percutánea

GENERALIDADES Infarto Agudo del miocardio es proceso dinámico Pronóstico determinado por tamaño del infarto Restauración de patencia coronaria Recanalización en ventana de tratamiento estrecha TIEMPO

EKG Tiempo de tratamiento ESTUDIOS TROMBOLISIS Vidas salvadas por 1000 pacientes tratados Disminución de mortalidad hasta en un 50% Lancet 343:311,1994 49 37 8 -14 35 25 19 18 BBB Ant ST­ Inf ST­ ST Depr 0-1hr 2-3hr 4-6hr 7-12hr -20 -10 10 20 30 40 50 EKG Tiempo de tratamiento

ESTUDIOS TROMBOLISIS Fallas de terapia Subgrupos de pacientes no obtienen beneficio claro con tratamiento trombolitico 30-40% de pacientes tratados no consiguen recanalización completa y reperfusión MORTALIDAD 2 VECES MAYOR Reoclusión Riesgo de hemorragia cerebral 1 por cada 150-200 pacientes

FLUJO TIMI A LOS 90 MINUTOS DE RECIBIR rT-PA Despite its relationship to clinical outcomes, the assessment of the TIMI flow grades can be quite variable. Shown here is the variability in the assessment of TIMI grade 3 flow for the same drug, front loaded rt-PA. The rate of TIMI grade 3 flow varies from a high of 78% in some trials to a low of 39% in others. The TIMI core lab has consistently reported rates of 60% which approximates the mean value of 60% across all trials.

FLUJO TIMI 3 DEPENDIENDO DE TROMBOLITICO A 90 MINUTOS

ESTUDIOS CON INTERVENCION PERCUTANEA Segura y eficaz Se obtiene recanalización completa y flujo timi 3 en 90% de pacientes Puntos finales combinados de muerte/IM/ECV a 30 días mas bajos que con terapia trombolítica si es centro especializado Tendencia a menor mortalidad cuando se compara con terapia trombolítica

ESTUDIOS CON INTERVENCION PERCUTANEA Fallas de terapia Disponibilidad En menos de 25% de hospitales en USA En menos de 10% de hospitales de Europa Remisión a tercer nivel para intervención coronaria percutánea Tiempo Seguridad PRAGUE - DANAMI II Tiempo Puerta - Balón

N=27,080 P < 0.00001 IMPORTANCIA DE RESTAURACIÓN COMPLETA Y RAPIDA DE PERFUSION MIOCARDICA NRMI-2: Angioplastia primaria. Tiempo puerta-balon Vs Mortalidad N=27,080 P < 0.00001 Lecture Notes Shown here are the raw absolute mortality rates for a variety of door to balloon times. References 1. Cannon CP et al, JAMA 2000 Tiempo puerta-balón (minutos) JAMA 2000; 283:2941-7.

Tiempo para reperfusión (h) Tiempo para reperfusión (h) ACTP primaria para IAM con elevación del ST Tiempo para reperfusión y mortalidad a 30 días CADILLAC Zwolle 6 12 n=2,002 n=1,791 1994-2001 5 10 9.6 4 P=0.04 ( 3h v  3h) 8 P<0.001 Mortalidad (%) 3 6 5.6 2.3 2.2 2 4 3.1 2.5 0.9 1 2 <3 3-6 >6 <2 2-4 4-6 >6 Tiempo para reperfusión (h) Tiempo para reperfusión (h) Brodie BR, et al. J Am Coll Cardiol. 2003;41(suppl A):368A. De Luca G, et al. J Am Coll Cardiol. 2003;41(suppl A):368A.

Reperfusión coronaria ESTRATEGIAS Reperfusión coronaria Completa Rápida (mortalidad tiempo dependiente)

ACORTAMIENTO DE TIEMPO DE APERTURA Y RESTAURACION COMPLETA DEL FLUJO Aprovecha rápida disponibilidad y utilización de trombolítico para restaurar algún tipo de flujo miocárdico acoplado con restauración más completa posterior con intervención coronaria percutánea Intervencion percutánea Diagnostico de Infarto Agudo Terapia farmacológica* Coronariografía Lecture Notes Previous sections of this material have established the following principles: The major determinants of reperfusion’s ability to improve clinical outcome are: The rate of full infarct artery physiological flow restoration (TIMI grade 3 flow) The speed with which such flow is restored following thrombotic occlusion Fibrinolytic therapy can generally be initiated much faster than primary angioplasty (with or without stenting). Primary angioplasty produces significantly higher patency rates. An optimal reperfusion strategy might consist of: Initial administration in the ED of one or more pharmacological promoters of reperfusion Subsequent evaluation of the patient by cardiac catheterization and, if indicated, the use of mechanical coronary intervention for further reperfusion therapy. Agents investigated to promote patency while arrangements are made for urgent catheter laboratory procedures include megadose heparin, the GP IIb/IIIa receptor inhibitorts, and low-dose fibrinolytics Otro tratamiento *Antitrombinicos, antiplaquetarios y fibrinolíticos.

En ACTP primaria y rescate flujo timi PRE asociado a mortalidad ANGIOPLASTIA FACILITADA Hallazgos angiográficos pre intervencionismo y mortalidad 1 2 4 6 94 98 100 90 Log-rank P for trend P=0.009 Supervivencia (%) TIMI 0/1 (1,657) TIMI 3 (n=375) TIMI 2 (n=295) Meses 92 96 4.4% 0.5% 2.8% 3 5 En ACTP primaria y rescate flujo timi PRE asociado a mortalidad Stone GW, et al. Circulation. 2001;104:636-641.

En ACTP primaria y rescate flujo timi PRE asociado a mortalidad ANGIOPLASTIA FACILITADA Hallazgos angiográficos pre intervencionismo y mortalidad 1.0 1.0 0.9 0.9 Supervivencia Supervivencia 0.8 TFG 2 0.8 3- way log-rank P=0.0013 TFG 3 TMPG 2/3 Log-rank P=0.03 TFG 0/1 TMPG 0/1 0.7 0.7 0.5 1.0 1.5 2.0 0.5 1.0 1.5 2.0 En ACTP primaria y rescate flujo timi PRE asociado a mortalidad Gibson CM, et al. Circulation. 2002;105:1909-1913.

9,3 % 9.3% 6,1 % 6.1% %Mortalidad 3,7 % 3.7% TIMI 0 TIMI 1 TIMI 2 Oclusion Penetracion Flujo Lento Flujo normal 9,3 % 9.3% P=0.003 vs TIMI 0/1 6,1 % 6.1% p<0.0001 vs TIMI 0/1 p<0.0001 vs TIMI 2 %Mortalidad 3,7 % 3.7% This pooled analysis of nearly 5,500 patients shows that the achievement of TIMI grade 3 flow is associated with improved outcomes in the setting of acute MI. The outcomes of TIMI grade 2 flow are intermediate between TIMI grade 0/1 flow and TIMI grade 3 flow. 10 16 33 34 44 4 8 27 13 19 9 15 18 29 34 Team 2 German TIM I 1,4 5,10B GUSTO 1 TIM I 1,4 5,10B Team 2 German TIM I 1,4 5,10B Team 2 TAM I 1-7 GUSTO 1 TAM I 1-7 German GUSTO 1 TAM I 1-7

ESTUDIOS INICIALES CON TRATAMIENTO COMBINADO EUROPEAN CONSERVATIVE SWIFT

A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. TAMI 386 pacientes con IAM tratados con 150 mgr r-TPA 2.95 +/- 1.1 horas de comienzo de síntomas CORONARIOGRAFIA. Patencia del vaso. 288 pacientes (75%) 197 pacientes con lesion por angiografía ACTP inmediata (n=99) ACTP deferida (n=98) Lecture Notes The study design is shown here. High-risk ST elevation MI patients (>4 mm elevation), with Sx < 12 hrs were enrolled in the study if transfer could be accomplished within < 3 hours. Patients were randomized to treatment with either 1) lytic therapy with front-loaded tPA 100 mg. (n=782) or 2) primary PCI with transfer (n=567), or primary PCI without transfer (n=223). Reoclusion/ACTP urgencia/Función ventricular izquierda global Topol EJ, et all. N Engl J Med 1987;317:581-8

TAMI. RESULTADOS REOCLUSION ACTP URGENCIAS FUNCION VENTRICULAR DEPRIMIDA P=0.5 P=0.2 P=0.01 Lecture Notes Shown here are the primary results of the trial. At both sites where patients were transferred as well as in those sites that did not require transfer, there was a reduction in the composite endpoint of 30 day death/recurrent MI and stroke. N=99 N=98 N=99 N=98 N=99 N=98 ACTP inmediata ACTP deferida ACTP inmediata ACTP deferida ACTP inmediata ACTP deferida Topol EJ, et all. N Engl J Med 1987;317:581-8

TRATAMIENTO CONSERVADOR 180 de 183 Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. European Cooperative Study 367 pacientes con IAM tratados con 100 mgr r-TPA 156 minutos de comienzo de síntomas CORONARIOGRAFIA 180 de 183 TRATAMIENTO CONSERVADOR 180 de 183 INTERVENCIONISMO Seguimiento Lecture Notes The study design is shown here. High-risk ST elevation MI patients (>4 mm elevation), with Sx < 12 hrs were enrolled in the study if transfer could be accomplished within < 3 hours. Patients were randomized to treatment with either 1) lytic therapy with front-loaded tPA 100 mg. (n=782) or 2) primary PCI with transfer (n=567), or primary PCI without transfer (n=223). Reoclusion/Isquemia recurrente/Sangrado y complicaciones/mortalidad Simoons ML, Arnold AE, Betriu A, et al, Lancet 1988;1:197-203

European Cooperative Study Resultados REOCLUSION EN GRUPO ACTP ISQUEMIA/SANGRADO HIPOTENSION FUNCION VENTRICULAR DEPRIMIDA P=0.01 P=0.02 Lecture Notes Shown here are the primary results of the trial. At both sites where patients were transferred as well as in those sites that did not require transfer, there was a reduction in the composite endpoint of 30 day death/recurrent MI and stroke. N=99 N=98 N=99 N=98 Transitoria Definitiva ACTP inmediata Tratamiento Médico ACTP inmediata Tratamiento Médico Simoons ML, Arnold AE, Betriu A, et al, Lancet 1988;1:197-203

SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT TRIAL 800 pacientes con IAM tratados con 30 UDS ANISTREPLASE 156 minutos de comienzo de síntomas CORONARIOGRAFIA 169 ACTP y 69 CABG TRATAMIENTO CONSERVADOR 403 169 ACTP 69 CABG Seguimiento Lecture Notes The study design is shown here. High-risk ST elevation MI patients (>4 mm elevation), with Sx < 12 hrs were enrolled in the study if transfer could be accomplished within < 3 hours. Patients were randomized to treatment with either 1) lytic therapy with front-loaded tPA 100 mg. (n=782) or 2) primary PCI with transfer (n=567), or primary PCI without transfer (n=223). Seguimiento Muerte o reinfarto a 12 meses Simoons ML, Arnold AE, Betriu A, et al, Lancet 1988;1:197-203

SWIFT TRIAL Resultados MORTALIDAD A 12 MESES REINFARTO A 12 MESES ESTANCIA HOSPITALARIA P=0.4 P=0.01 P=0.6 Lecture Notes Shown here are the primary results of the trial. At both sites where patients were transferred as well as in those sites that did not require transfer, there was a reduction in the composite endpoint of 30 day death/recurrent MI and stroke. ACTP inmediata Tratamiento Médico ACTP inmediata Tratamiento Médico ACTP inmediata Tratamiento Médico Simoons ML, Arnold AE, Betriu A, et al, Lancet 1988;1:197-203

ESTUDIOS POSTERIORES INTERVENCIONISMO CORONARIO PERCUTANEO Mejores facilidades técnicas STENTS TRATAMIENTO TROMBOLITICO Mejoría en fibrinolíticos Nuevos Agentes Inhibidores de glicoproteína IIB IIIA Inhibidores directos de trombina

EPIC RAPPORT ADMIRAL CADILLAC ESTUDIOS CON INHIBIDORES DE GLICOPROTEINA IIB-IIIA MAS INTERVENCIONISMO CORONARIO PERCUTANEO EPIC RAPPORT ADMIRAL CADILLAC

A D M I R L Abciximab before Direct Angioplasty and Stenting in ADMIRAL ESTUDIO ADMIRAL A D M I R L Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long term follow-up

ADMIRAL DISEÑO IAM < 12 hours aleatorizaciòn Abciximab (n=150) + 0.25 mg/kg bolo +inf 0.125 mg/kg/min(12h) + Heparina, ASA, Ticlopidina Placebo (n=150) + Heparina, ASA, Ticlopidina Coronariografia PTCA + Stent Coronariografia PTCA + Stent Coronariografia a 24 h y 6 Meses Coronariografia a 24 h y 6 Meses Evaluaciòn clìnica (24 h, 30 Dias y 6 meses

Tiempo de tratamientos Abciximab n = 150 Placebo n = 150 Tiempo de comienzo de dolor a: A tratamiento (hrs) 3.2 + 2.5 3.5 + 2.4 A bolo (hrs) 3.7 + 2.1 4.1 + 2.5 A coronariografia (hrs) 3.9 + 2.1 4.4 + 2.6 A ACTP (hrs) 4.1 + 2.1 4.6 + 2.6

RESULTADOS ANGIOGRAFICO FLUJO TIMI 3 10.3 83.7 84.4 89.9 82.5 21.0 90.4 92.0 20 40 60 80 100 Inicial Luego ACTP Luego STENT 24-horas % pacientes Placebo Abciximab p < 0.02 p < 0.01

FUNCION VENTRICULAR IZQUIERDA Abciximab n = 150 Placebo p < 0.05 51.4 54.6 25 50 75 24-horas Feyeccion (%)

PUNTOS FINALES PRIMARIOS A 30 DÍAS 7.3 15.3 5 10 15 20 % of Pacientes p = 0.02 - 52.3 % Muerte, IM recurrente, Nueva revascularización Placebo n = 150 Abciximab

PUNTOS FINALES PRIMARIOS A 30 DÍAS EN FORMA INDIVIDUAL 7.3 3.3 2.0 6.7 1.3 5 10 Muerte IM recurrente Revasc vaso urgente % of Pacientes Placebo Abciximab p = 0.33 - 54.8% p = 0.65 - 35.0% p = 0.02 - 80.0%

SANGRADO 1.3 6.7 2.6 4.0 2 4 6 8 10 Mayor Menor % of Pacientes Placebo 2 4 6 8 10 Mayor Menor % of Pacientes Placebo Abciximab p = 0.50 p = 0.02

CONCLUSIONES Uso de abxicimab junto con ACTP+STENT en pacientes con IAM mejora Tasa flujo TIMI 3 temprana Función ventricular izquierda Resultados clínicos a 30 dìas

DISEÑO CADILLAC Controlled Abciximab and Device Investigation to Lower Late Angioplasty Combinations Angioplastia con Balon (+ abciximab) vs Angioplastia con STENT (+ abciximab) Criterios Inclusión Lecture Notes The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Combinations (CADILLAC) trial is a multicenter trial comparison of PTCA  abciximab versus stenting  abciximab in the setting of AMI. Of 2,625 consecutive patients with AMI, 2,081 patients met the clinical and angiographic eligibility criteria. Edad >18 años Dolor correspondiente a IAM (duraciòn > 30 min < 12 horas) Arteria coronaria nativa > 2.5 mm, < 4.0 mm Longitud de lesiòn < 70 mm

Barragan et al Circ 2000; 102: II-662 CADILLAC Flujo TIMI 3 Barragan et al Circ 2000; 102: II-662 p = NS p = NS CADILLAC

Barragan et al Circ 2000; 102: II-662 DISMINUCION RIESGO RELATIVO 14% CADILLAC Mortalidad 6 meses Barragan et al Circ 2000; 102: II-662 p=NS DISMINUCION RIESGO RELATIVO 14% There was no subacute thrombosis in the stent/abciximab group.

ACTP+STENT+ abciximab (n=525) RESULTADOS CADILLAC ACTP1,3 (n=517 ) ACTP + Abciximab (n=528 ) ACTP+ STENT3 (n=511 ) ACTP+STENT+ abciximab (n=525) Flujo TIMI 3 94% 92% 92% 96.7% Isquemia Recurrente 4.5% 1.5% 3.9% 1.2% Necesidad de Nueva revascularización Lecture Notes As in the PAMI-STENT trial, the CADILLAC trial demonstrated that primary stenting produced a marked increase in minimal lumen diameter as compared to PTCA (2.7 mm vs 2.15 mm, respectively). (Stone et al, 1999) Additionally, primary stenting was associated with a lower rate of TIMI grade 3 flow. This lower rate of TIMI grade 3 flow did not translate into early mortality. The addition of abciximab reversed the effect of stenting on TIMI grade 3 flow, resulting in the highest rate of TIMI grade 3 flow in any of the 4 treatment arms. The rates of in-hospital mortality, stroke, and reinfarction were similar among the 4 cohorts as was the incidence of bleeding. 2.3% 0.2% 0.8% 0.2%

METANALISIS CON IIB IIIA MUERTE, REINFARTO, REVASCULARIZACION URGENTE (30 días) Lecture Notes As in the PAMI-STENT trial, the CADILLAC trial demonstrated that primary stenting produced a marked increase in minimal lumen diameter as compared to PTCA (2.7 mm vs 2.15 mm, respectively). (Stone et al, 1999) Additionally, primary stenting was associated with a lower rate of TIMI grade 3 flow. This lower rate of TIMI grade 3 flow did not translate into early mortality. The addition of abciximab reversed the effect of stenting on TIMI grade 3 flow, resulting in the highest rate of TIMI grade 3 flow in any of the 4 treatment arms. The rates of in-hospital mortality, stroke, and reinfarction were similar among the 4 cohorts as was the incidence of bleeding. Kandsari,D et all. Am Heart J 2004;147:457–62

METANALISIS CON IIB IIIA MUERTE, REINFARTO, REVASCULARIZACION URGENTE (6 meses) Lecture Notes As in the PAMI-STENT trial, the CADILLAC trial demonstrated that primary stenting produced a marked increase in minimal lumen diameter as compared to PTCA (2.7 mm vs 2.15 mm, respectively). (Stone et al, 1999) Additionally, primary stenting was associated with a lower rate of TIMI grade 3 flow. This lower rate of TIMI grade 3 flow did not translate into early mortality. The addition of abciximab reversed the effect of stenting on TIMI grade 3 flow, resulting in the highest rate of TIMI grade 3 flow in any of the 4 treatment arms. The rates of in-hospital mortality, stroke, and reinfarction were similar among the 4 cohorts as was the incidence of bleeding. Kandsari,D et all. Am Heart J 2004;147:457–62

METANALISIS CON IIB IIIA MUERTE, REINFARTO, REVASCULARIZACION URGENTE Lecture Notes As in the PAMI-STENT trial, the CADILLAC trial demonstrated that primary stenting produced a marked increase in minimal lumen diameter as compared to PTCA (2.7 mm vs 2.15 mm, respectively). (Stone et al, 1999) Additionally, primary stenting was associated with a lower rate of TIMI grade 3 flow. This lower rate of TIMI grade 3 flow did not translate into early mortality. The addition of abciximab reversed the effect of stenting on TIMI grade 3 flow, resulting in the highest rate of TIMI grade 3 flow in any of the 4 treatment arms. The rates of in-hospital mortality, stroke, and reinfarction were similar among the 4 cohorts as was the incidence of bleeding. Kandsari,D et all. Am Heart J2004;147:457–62

RECONOCIMIENTO DE POTENCIAL EFECTO SINERGICO BENEFICO CON TERAPIA COMBINADA PACT SPEED TIMI 10B /14B

Plasminogen-Activator Angioplasty Compatibility Trial (PACT) Paciente con infarto agudo miocardio n=606 ASA, heparina IV Aleatorización t-PA 50 mg bolo Placebo bolo Coronariografía inmediata Lecture Notes The major advantages of fibrinolytic therapyincluding ease and speed of administration and universal availabilityand PTCAincluding good reperfusion ratescould be utilized if these interventions were combined effectively. The Plasminogen Activator Angioplasty Compatibility Trial (PACT) was designed with 2 primary goals: (1) to determine whether reperfusion could be achieved earlier if a fibrinolytic agent were used enroute to the catheterization laboratory, and (2) to determine if the administration of a fibrinolytic agent would be detrimental to the results of PTCA. (Ross et al, 1999) Inclusion criteria included the following: AMI symptom onset within 6 hours of presentation, age less than 75 years, no history of cerebrovascular disease or prior CABG surgery. All 606 patients received a standard regimen of aspirin and heparin prior to randomization to one of two treatment arms: (1) 50-mg bolus of t-PA, or (2) matched placebo bolus. All patients then underwent urgent angiography. If TIMI grade 3 flow was observed, the patient received a second 50-mg bolus of drug. If TIMI grade flow 0/1/2 was observed, PTCA was performed immediately. Outcomes were assessed at 5 to 7 days via angiography and ventriculography and by exercise testing at 6 weeks. TIMI 3 TIMI 0, 1, 2 Segundo bolo de trombolitico Angioplastia inmediata Seguimiento con Coronariografía a los 5-7 días Prueba de esfuerzo 6 semana Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

Patencia de la arteria a tratar al llegar a hemodinámica FLUJO TIMI 61 34.3 Lecture Notes As expected, prior to PTCA, a significantly greater percentage of patients treated with t-PA (almost twice as many) had achieved TIMI grade 2 or 3 flow compared with placebo-treated patients (61% versus 34%, respectively; P=0.001) (Ross et al, 1999) *P<0.001. Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

RESULTADO TECNICO DE LA ANGIOPLASTIA P=NS % of Pacientes Lecture Notes There were no significant differences in the technical success of PTCA between the t-PA and placebo groups. Upon leaving the catheterization laboratory, 76% of patients in the t-PA group and 79% of patients in the placebo group had achieved TIMI grade 3 flow (P=0.62). Conversion of closed vessels (TIMI grade 2 or 3 flow) was 92.8% in the t-PA group versus 94.6% in the placebo group (P=0.52). (Ross et al 1999) However, among patients who achieved TIMI grade 3 flow, the medical time to reperfusion was significantly shorter for t-PA (without PTCA) than for PTCA alone—51 minutes versus 93 minutes, respectively (P<0.0001). TIMI 2, 3 TIMI 3 TIMI 2 TIMI 3 Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

Fracción de expulsión % FUNCION VENTRICULAR A LOS 7 DIAS DEPENDIENDO DE FLUJO TIMI PRE Y POST PROCEDIMIENTO FRACCION DE EXPULSION P=0.004 Fracción de expulsión % Lecture Notes Patients in the t-PA-treated group experienced a significant improvement in left ventricular ejection fraction (LVEF) at 1 week following AMI (convalescent LVEF). This beneficial effect resulted from the t-PA group’s having a higher number of patients with TIMI grade 3 flow earlier, ie, on arrival to the catheterization laboratory (33% versus 15%; P<0.001). (Ross et al, 1999) Patients arriving at the catheterization laboratory with TIMI grade 3 flow already established had a convalescent LVEF of 62.4%, compared with 57.9% for those who achieved TIMI grade 3 flow only after PTCA (P=0.004). Never achieving TIMI grade 2 flow was associated with the lowest initial LVEF (55.8%) and convalescent LVEF (54.7%). In addition, LVEF was predicted by the timing of the PTCA. For the 12% of patients who had PTCA within 1 hour following study drug, the mean convalescent LVEF was 62.5% compared with 57.3% for patients delayed more than 1 hour (P<0.005). Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

PACT: Eventos adversos t-PA Placebo Valor p Sangrado Mayor 12.9% 13.5% 0.84 ECV 0.7% 0.7% 0.99 Sangrado Intracraneal 0.3% 0.3% 0.99 Lecture Notes There were no differences between t-PA and placebo groups with respect to adverse events, including major bleeding and stroke. The study showed that treatment with t-PA significantly improved early patency rate, even prior to patient arrival at the catheterization laboratory. The technical success of PTCA was not diminished by pretreatment with t-PA and there was not increase in complications when the procedures were combined. The potential applicability of this regimen is widespread, as epidemiologic studies have demonstrated that the time to PTCA is significantly longer in the community hospital setting. 7.3% 7.2% 0.98 Revascularización urgente Muerte Hospitalaria 3.6% 3.0% 0.64 Muerte a 30 días 3.6% 3.3% 0.81 Ross AM, et al. J Am Coll Cardiol. 1999;34:1954-1962.

CONCLUSION PACT Terapia combinada segura: no aumenta riesgo de Sangrado cerebral CABG Reoclusión Necesidad de nuevo intervencionismo percutáneo Valor especial para contrarestar el retraso en tiempo que conlleva realizar intervencion coronaria percutánea Pronósticos mejores si arteria esta abierta antes de intervencionismo percutáneo Lecture Notes Immediate pharmacological therapies aimed at promoting infarct artery patency during common delays preceding primary angioplasty are feasible. By promoting earlier patency, these precatheterization treatments enhance preservation of left ventricular function without adversely influencing the course, conduct, or outcome of mechanical interventional procedures. Currently, the strongest evidence for this approach comes from studies in which bolus t-PA was part of the “prejunctive” regimen, but other fibrinolytics are being investigated for this role.

Estudio piloto GUSTO IV

Aumento de incidencia y velocidad de reperfusiòn SPEED HIPOTESIS PLANTEADA Aumento de incidencia y velocidad de reperfusiòn Reducción de mortalidad Terapia segura facilitando intervención percutánea temprana Exito de intervenciòn percutánea es menor en vasos con flujo TIMI 0-1 Vs TIMI 2-3 ACC 1999: Oral Presentation

Abciximab standard dose PROTOCOLO SPEED SPEED IM AGUDO ELEVACION ST MENOS DE 6 horas DE SINTOMAS 530 PACIENTES 1:1 Aleatorización r-PA 10 + 10 U Heparina 70 U/kg Abciximab standard dose r-PA 5 + 5 U Heparina 40 – 60 U/kg Angiografìa a los 60 –90 minutos 464 PACIENTES ACTP +STENT si indicado 323 PACIENTES Administrado en Urgencias r-PA control Abxicimab control ACC 1999: Oral Presentation

FLUJO TIMI 3 A LOS 60 –90 MINUTOS SPEED FLUJO TIMI 3 A LOS 60 –90 MINUTOS Resultado angiográfico p = 0.06 p = 0.2 n = 107 n = 103 n = 75 n = 66 r-PA solo 60 U Hep Abciximab + r-PA 5 + 5 40 U Hep Abciximab + r-PA 5 + 5 Abciximab solo

PRONOSTICOS CLINICOS A 30 DIAS SPEED PRONOSTICOS CLINICOS A 30 DIAS Abciximab r-PA 5 + 5 60 U Hep Abciximab r-PA 5 + 5 40 U Hep r-PA solo Abciximab solo Muerte 5.6% 4.4% 2.6% 3.2% Reinfarto 2.8% 1.7% 1.3% 0% Isquemia severa 2.8% 4.3% 2.6% 6.4% Requriendo urgente Revascularizacion COMBINADO 11.2% 9.6% 5.3% 9.5%

Intervenciòn coronaria percutànea facilitada SPEED Intervenciòn coronaria percutànea facilitada PRONOSTICO FLUJO TIMI PRE PROCEDIMIENTO 0-1 (n = 123) 2-3 (n = 198) Post Procedimiento p Estenosis final 10 (0, 25) 0 (0, 20) 0.0001 FLUJO TIMI 3 83% 95% 0.001 STENTS 73% 81% 0.09 Exito procedimiento* 81% 93% 0.001 * Estenosis de < de 50% con flujo TIMI 3 ACC 1999: Oral Presentation

FLUJO TIMI 3 EN EL TIEMPO DEPENDIENDO DE TERAPIA SPEED FLUJO TIMI 3 EN EL TIEMPO DEPENDIENDO DE TERAPIA

Early Coronary Intervention Following Pharmacologic Therapy for Acute Myocardial Infarction (The Combined TIMI 10B–TIMI 14 Experience) Trombolitico Tenecteplase R-TPA Brauwald. Am J Cardiol 2001;88:831–836)

The CombinedTIMI 10B–TIMI 14 Experience Comparación pacientes con flujo TIMI 0-1 a 90 minutos tratados médicamente Vs con intervención coronaria percutánea P=0,011 P=0,010 Brauwald. Am J Cardiol 2001;88:831–836)

The Combined TIMI 10B–TIMI 14 Experience Odds ratio a 30 días en pacientes con flujo TIMI 3 a los 90 minuto tratados luego con PCI vs Medicamente Brauwald. Am J Cardiol 2001;88:831–836)

PUNTOS FINALES A 30 DIAS COMPARANDO DIFERENTES TIPOS DE TERAPIAS PUNTOS FINALES A 30 DIAS COMPARANDO DIFERENTES TIPOS DE TERAPIAS. MUERTE x x x x x x 0 0,5 1 2 4 10

PUNTOS FINALES A 30 DIAS COMPARANDO DIFERENTES TIPOS DE TERAPIAS PUNTOS FINALES A 30 DIAS COMPARANDO DIFERENTES TIPOS DE TERAPIAS. MUERTE O REINFARTO x x x x x x 0 0,5 1 2 4 10

ESTUDIOS EN CURSO ASSENT 4 TNK Heparina/ASA ADVANCE TNK + Integrilin TITAN Integrilin en Urgencias Integrilin en hemodinamica FINESSE r-PA r-PA + abciximab en urgencias vs hemodinamica Shown here are the preliminary designs of upcoming primary PCI trials which should address issues surrounding the efficacy of “facilitated PCI”.

DISCUSION Cual es la mejor estrategia farmacológica para maximizar la posibilidad de obtener flujo TIMI 3 previa a intervencion coronaria percutánea en infarto agudo de miocardio con elevación del ST TROMBOLITICOS Dosis máxima. intermedia INHIBIDORES DE GP IIB IIIA CADILLAC (-). ADMIRAL (+) TRATAMIENTO COMBINADO Seguridad TIMI 14 (+). ASSENT-III GUSTO IV (+/-)

DISCUSION Puede ampliarse ventana terapeutica inicial de intervencion percutánea con medidas farmacológicas para obtener resultados post intervencion òptimos Cual es la mejor estrategia de tratamiento para el paciente mayor de 75 años .