Trial Of Routine Angioplasty And Stenting After Fibrinolysis To Enhance Reperfusion In Acute Myocardial Infarction Research Articles

Long-term Follow-up of the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

BackgroundThe Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) demonstrated superiority of routine early coronary angiography (and percutaneous coronary intervention [PCI]) compared with standard therapy in fibrinolytic-treated patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The aim of the current study was to evaluate the long-term (>7 year) effects of an early invasive strategy. MethodsWe linked the study cohort and administrative datasets to assess long-term follow-up status including repeat procedures, hospitalizations, and major adverse cardiovascular events (MACE). Kaplan-Meier and Cox regression analysis were used to evaluate the relationship between randomized treatment and long-term adverse outcomes. ResultsA total of 881 patients had long-term follow-up and were included in our study. After a mean follow-up of 7.8 years, there were no significant differences in death, myocardial infarction (MI), unstable angina, stroke, transient ischemic attack (TIA), or heart failure admissions (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.73–1.13]; P = 0.41) between those randomized to an early invasive vs standard treatment strategy. Following the index hospitalization, there were no significant difference in the rates of coronary revascularization between the early invasive and the standard therapy groups (81 [19.3%] vs 76 [17.9%]; P = 0.61). ConclusionsDespite the short-term benefit and safety of an early invasive strategy in patients with STEMI receiving fibrinolysis, no statistically significant differences in MACE were observed over 7.8 years.

Efficacy of Early Invasive Management After Fibrinolysis for ST-Segment Elevation Myocardial Infarction in Relation to Initial Troponin Status

BackgroundWe examined whether the efficacy of an early invasive strategy after fibrinolysis in ST-segment elevation myocardial infarction (STEMI) differs in relation to the initial troponin status. MethodsIn the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), patients with STEMI presenting to a non-percutaneous coronary intervention (PCI)-capable hospital who received fibrinolysis were randomized to either a pharmacoinvasive or standard strategy for subsequent angiography and PCI. In this post hoc subgroup analysis, we compared the efficacy of these strategies in relation to the initial troponin status at hospital presentation for the primary composite end point of mortality, reinfarction, recurrent ischemia, heart failure, and cardiogenic shock at 30 days. We assessed the heterogeneity of treatment effect with initial troponin status using the Breslow-Day test and tested for interaction after adjustment for baseline Global Registry of Acute Coronary Events (GRACE) risk score. ResultsAmong 1059 patients, those with abnormal initial troponin levels (n = 514 [48.5%]) were older with worse Killip class, had a longer time from symptom onset to fibrinolysis, and had higher GRACE and Thrombolysis In Myocardial Infarction risk scores. Patients with abnormal troponin levels had higher rates of the primary end point (17.5% vs 10.8%; P = 0.002) and cumulative mortality or reinfarction at 1 year (14.0% vs 8.1%; P = 0.003). In stratified analyses, pharmacoinvasive management reduced the primary end point only among patients with normal initial troponin status. However, there was no significant treatment heterogeneity (all P ≥ 0.10) and no interaction between initial troponin status and treatment assignment after adjusting for GRACE risk score. ConclusionsPatients with STEMI and abnormal initial troponin levels had worse short-term and long-term outcomes. Accounting for overall baseline risk with the GRACE risk score, troponin status did not modulate the efficacy of pharmacoinvasive management.

Efficacy and Safety of a Routine Early Invasive Strategy in Relation to Time from Symptom Onset to Fibrinolysis (a Subgroup Analysis of TRANSFER-AMI)

The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis.

EFFICACY AND SAFETY OF A ROUTINE EARLY INVASIVE STRATEGY IN RELATION TO TIME FROM SYMPTOM ONSET TO FIBRINOLYSIS: A SUBGROUP ANALYSIS FROM TRANSFER-AMI

Randomized controlled trials have demonstrated the clinical benefit of a routine early invasive strategy in patients receiving fibrinolysis for ST-elevation myocardial infarction (STEMI). However, the treatment effect of fibrinolysis is highly time sensitive - efficacy decreases as the time interval from symptom onset to fibrinolysis lengthens. Whether the effect of a routine early invasive strategy, as an adjunct to fibrinolysis, also varies in relation to this time interval is not well understood. We therefore sought to evaluate the efficacy and safety of a routine early invasive strategy in relation to time from symptom onset to fibrinolysis. The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1059 STEMI patients to an early invasive strategy - consisting of routine early transfer for coronary angiography and percutaneous coronary intervention (PCI) if needed within 6 hours of fibrinolysis - or standard therapy post-fibrinolysis. The primary endpoint was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post-hoc subgroup analysis of TRANSFER-AMI, we evaluated efficacy and safety outcomes after stratification by the time elapsed from symptom onset to fibrinolysis (<2 vs ≥2 hours). Of 1059 patients (median age 57 years, 80% male), 557 (53%) and 502 (47%) received fibrinolysis <2 hours (median 1.25 hours, IQR 0.97-1.58 hours) and ≥2 hours (median 3.24 hours, IQR 2.43-4.80 hours) after symptom onset, respectively. Patients receiving fibrinolysis <2 hours after symptom onset were younger, and more likely to be male and have had a prior myocardial infarction and PCI. Patients who received fibrinolysis ≥2 hours after symptom onset had higher GRACE risk scores (127 vs 122, p=0.004). Baseline characteristics and treatment variables were well balanced between treatment arms within each symptom-to-fibrinolysis time stratum. The efficacy of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary endpoint, death at 30 days, or the composite of death or reinfarction at 30 days, 6 months, or 1 year (Figure). The effect of an early invasive strategy on TIMI major bleeding was also similar between strata. The efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time from symptom onset to fibrinolysis. A routine early invasive strategy is safe and effective even if fibrinolytic is administered shortly (<2 hours) after symptom onset.

Efficacy of an Early Invasive Strategy After Fibrinolysis in ST-Elevation Myocardial Infarction Relative to the Extent of Coronary Artery Disease

BackgroundA strategy of early transfer for coronary angiography and intervention is superior to a standard approach of delayed coronary angiography after fibrinolysis for ST-elevation myocardial infarction (STEMI). STEMI patients with lesions in noninfarct-related arteries have a worse prognosis compared with patients with single vessel disease. This study aimed to assess whether the benefits of an early invasive strategy differ in patients with single vessel and multivessel disease. MethodsThe Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized STEMI patients receiving fibrinolysis to a strategy of early transfer and coronary angiography vs a standard approach. In this post hoc analysis, we stratified 992 patients into 2 groups according to the presence or absence of multivessel disease. We compared the 2 groups in terms of baseline characteristics, in-hospital management, and patient outcomes, and tested for treatment heterogeneity. ResultsMultivessel disease was present in 369 (37%) patients. Patients with multivessel disease had a greater rate of the primary composite end point of in-hospital death, recurrence of infarction, recurrent ischemia, shock, or heart failure at 30 days (18.2% vs 10.8%; P < 0.001). An early invasive strategy was efficacious in both groups for the primary outcome. In multivariable analysis adjusting for Global Registry of Acute Coronary Events (GRACE) risk score, there was no significant treatment heterogeneity (all P interaction > 0.40) for the primary end point, or death/recurrence of infarction at 6 months and 1 year. ConclusionsMultivessel disease is present in a significant proportion of STEMI patients treated with fibrinolysis and is associated with worse outcomes. A strategy of early transfer and coronary intervention after fibrinolysis was beneficial regardless of the presence or absence of multivessel disease.

Comparison of the Efficacy of Pharmacoinvasive Management for ST-Segment Elevation Myocardial Infarction in Smokers Versus Non-Smokers (from the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction)

Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers (13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST-segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers.

Efficacy and safety of a routine early invasive strategy after fibrinolysis stratified by glycoprotein IIb/IIIa inhibitor use during percutaneous coronary intervention: a pre-specified subgroup analysis of the TRANSFER-AMI randomised controlled trial

ObjectiveWe evaluated the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to glycoprotein (GP) IIb/IIIa inhibitor use.MethodsThe Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance...

Clinical outcomes and cost implications of routine early PCI after fibrinolysis: One-year follow-up of the Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) study

In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI). We report prespecified secondary clinical outcomes and cost implications of r-PCI compared with s-PCI from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was calculated based on a microcosting approach. Bootstrap method (5,000 samples) was used to calculate standard errors and 95% CI. At 1 year, rates of death or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%, P = .64) and subsequent revascularization after index hospitalization (6.9% vs 8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to $2,211). Since a greater proportion of patients were transported by air (vs land) in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional post hoc cost scenario analyses. In a scenario where patients are transported by land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the difference in cost per patient between r-PCI and s-PCI was estimated to be CAD $108 (95% CI, -$1,114 to $1,344). At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important.

Evaluation of early percutaneous coronary intervention vs. standard therapy after fibrinolysis for ST-segment elevation myocardial infarction: contribution of weighting the composite endpoint

The selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered. We analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44). This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.

Efficacy of early invasive management post-fibrinolysis in men versus women with ST-elevation myocardial infarction: A subgroup analysis from Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

The TRANSFER-AMI study demonstrated that early routine percutaneous coronary intervention post-fibrinolysis (pharmacoinvasive strategy) is superior to conservative management for ST-elevation myocardial infarction. However, it is not clear whether treatment efficacy differs between men and women. In this pre-specified subgroup analysis, we compared the efficacy of a pharmacoinvasive strategy in men versus women with acute ST-elevation myocardial infarction who were randomized to a pharmacoinvasive versus standard management following fibrinolysis. The primary end point was a composite of death, recurrent myocardial infarction, recurrent ischemia, heart failure and shock at 30 days. We tested for treatment heterogeneity between men and women using the Breslow-Day test. We also performed multivariable analysis adjusting for GRACE risk score and its interaction with treatment assignment, and evaluated for death/recurrent myocardial reinfarction as a secondary outcome. Of the 1059 patients, 843 were men and 216 were women. Compared to men, women were older, had worse Killip class, higher GRACE risk score, and higher rates of death and death/myocardial reinfarction at 30 days. The primary end point did not differ significantly between men and women (13.4% vs 16.7%, P = .22). Compared to standard treatment, a pharmacoinvasive strategy was associated with a lower rate of the primary end point in men (17.5% vs 9.4%, respectively, P < .001), but not in women (16.2% vs 17.1%, P = .86). There was a trend toward an interaction between treatment assignment and sex for the composite primary end point (P = .06). After adjustment for the significant interaction between GRACE risk score and treatment (P < .001), there was no significant interaction between sex and treatment for all the end points (all P > .40). The borderline heterogeneity in treatment efficacy of a pharmacoinvasive strategy in men versus women was no longer evident after adjustment for the difference in baseline risk. This suggests that sex per se was not an important determinant of the efficacy of a pharmacoinvasive strategy. Owing to the small number of women in this trial, further study in this area is needed.

248 Efficacy of early invasive management post-fibrinolysis in men versus women with ST-elevation myocardial infarction: A subgroup analysis from TRANSFER-AMI

The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) demonstrated that early routine percutaneous coronary intervention post-fibrinolysis (pharmacoinvasive strategy) is superior to conservative management for ST-elevation myocardial infarction (STEMI), although a post-hoc exploratory subgroup analysis suggests that higher risk patients may not benefit. In this pre-specified subgroup analysis, we compared the efficacy of this pharmacoinvasive strategy in men versus women.

Who should have a routine early invasive approach after fibrinolytic therapy?

This editorial refers to ‘Relationship between risk stratification at admission and treatment effects of early invasive management following fibrinolysis: insights from the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)’, by A.T. Yan et al. doi:10.1093/eurheartj/ehr008 Reperfusion therapy for patients with ST-segment elevation myocardial infarction (STEMI), especially with primary percutaneous coronary intervention (PCI), can reduce mortality by >25%. Earlier reperfusion provides greater benefit, particularly in the early hours of infarction.1 Of the large number of remaining questions about how best to apply reperfusion therapy for patients with acute STEMI, few are more important than how to manage the patient who presents to the hospital without PCI capability. When it can be done quickly, transfer for primary PCI is generally the best strategy.2 Yet all too often—70% of the time in the USA from 2005 to 20073—this patient is transferred for primary PCI with long delays (of >120 min first door to device) that rob the patient of the benefits of prompt reperfusion therapy with fibrinolysis. Even with fibrinolysis, whether and when to transfer to a PCI-capable centre, to perform angiography, and to perform PCI has been a topic of intense investigation. There have been at least three published meta-analyses4–6 in the past year of the modest-sized clinical trials that have randomly assigned patients following fibrinolysis to routine early vs. selective (or delayed) coronary angiography and …

Relationship between risk stratification at admission and treatment effects of early invasive management following fibrinolysis: insights from the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

We sought to determine the effectiveness of early routine percutaneous coronary intervention (PCI) post-fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to baseline risk status. In this post hoc subgroup analysis of Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), we stratified 1059 STEMI patients receiving tenecteplase into low-intermediate [Global Registry of Acute Coronary Events (GRACE) risk score<155; n=889] vs. high-risk (GRACE risk score ≥155; n=170) groups, based on the GRACE risk score for in-hospital mortality. There was a significant interaction between treatment assignment and risk status for the composite endpoint of death/re-MI at 30 days (P for interaction<0.001). Compared with the standard treatment, pharmacoinvasive therapy (early routine PCI) was associated with a lower rate of death/re-MI at 30 days in the low-intermediate risk stratum (8.1 vs. 2.9%, P<0.001), but a higher rate of death/re-MI in the high-risk group (13.8 vs. 27.8%, P=0.025). We found similar heterogeneity in the treatment effects on 30-day mortality and death/re-MI at 1 year (P for interaction=0.008 and 0.001, respectively), when the GRACE risk score was analysed as a continuous variable (P for interaction<0.001) and when patients were stratified by the Thrombolysis In Myocardial Infarction (TIMI) risk score (P for interaction=0.001). We observed a strong heterogeneity in the treatment effects of a pharmacoinvasive strategy after fibrinolysis for STEMI, which is associated with improved outcomes only among patients with a low-intermediate GRACE risk score. Conversely, the early invasive strategy is associated with worse outcomes in high-risk patients. These novel findings should be considered exploratory only and require confirmation in other trials and meta-analyses. http://www.clinicaltrials.gov/ct2/show/NCT00164190 ClinicalTrials.gov number, NCT00164190.

Drip‑and‑ship for acute ST‑segment myocardial infarction. The pharmacoinvasive strategy for patients treated with fibrinolytic therapy

Primary percutaneous coronary intervention (PCI) has been demonstrated to be superior to fibrinolytic therapy in reducing mortality in ST-segment elevation myocardial infarction (STEMI) when it can be performed rapidly. However, many STEMI patients present to hospitals without PCI capability and often cannot undergo PCI within the guideline-recommended timelines; instead, they receive fibrinolysis as the initial reperfusion therapy. Several studies have explored the potential of combining the best of both therapies by performing PCI soon after fibrinolysis, including TRANSFER-AMI (Trial of Routine Angioplasty and stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction). Patients (n = 1059) with anterior or high-risk inferior STEMI presenting to non-PCI centers within 12 h of symptom onset treated with tenecteplase and other standard antithrombotic therapies were randomized to either a pharmacoinvasive strategy (urgent transfer, angiography and PCI when appropriate within 6 h) or standard treatment (including rescue PCI, or angiography and PCI when appropriate beyond 24 h). The composite primary endpoint of 30-day death, reinfarction, recurrent ischemia, new or worsening heart failure, and cardiogenic shock occurred less frequently in the routine early PCI patients compared to the standard treatment patients (11.0% vs. 17.2%, P = 0.004). Based upon these findings, consistent with other studies, we believe that STEMI patients who cannot undergo timely primary PCI should receive prompt fibrinolysis followed by initiation of an immediate transfer to a PCI-capable hospital without waiting to see whether reperfusion is successful.

Reperfusion Strategies in ST-Elevation Myocardial Infarction

Reperfusion Strategies in ST-Elevation Myocardial Infarction

Abstract 6178: Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) - Six Month Outcomes

Patients who present with ST-elevation myocardial infarction to hospitals without percutaneous coronary intervention (PCI) often cannot undergo primary PCI in a timely manner and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis, using contemporary stents and pharmacotherapy, has not been studied in a large adequately powered randomized trial. To compare a pharmacoinvasive strategy of transfer for routine PCI within 6 hrs after fibrinolysis with standard treatment after fibrinolysis (including predefined criteria for rescue PCI). Pts presenting to non-PCI centres with STEMI within 12 hrs of symptom onset and with high-risk features were randomized to a pharmacoinvasive strategy (transfer for PCI within 6 hrs of fibrinolysis) or to standard treatment after fibrinolysis (which included rescue PCI as required for ongoing chest pain and &lt; 50% resolution of ST-elevation at 60 –90 minutes). For standard treatment pts who did not require rescue PCI, cardiac catheterization was encouraged beyond 24 hrs. All pts received ASA and antithrombin therapy (unfractionated heparin or enoxaparin for age &lt;75 yrs); use of upfront clopidogrel was strongly encouraged; all other therapies were left to the discretion of the treating physician. The primary endpoint was the 30-day composite of death, reinfarction, recurrent ischemia, heart failure or shock. All patients were contacted at 6-months and 1-year for death and reinfarction, and all events were independently adjudicated. 1,059 pts were enrolled as of December 31, 2007. The preliminary 30-day results were recently presented, showing a 45% reduction in the primary endpoint with the pharmacoinvasive strategy (10.6% vs. 16.6%, p=0.01), with no difference in major bleeding complications. This study is the largest randomized trial to date comparing a pharmacoinvasive strategy with standard care after fibrinolysis. The 6-month outcomes will demonstrate whether the significantly lower rates of ischemic complications seen with the pharmacoinvasive strategy at 30-days are sustained and translate into lower rates of death or reinfarction at 6 months.

Rationale and design of the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

Most patients with ST-elevation myocardial infarction present to hospitals without percutaneous coronary intervention (PCI) facilities and receive fibrinolysis. The role of routine early PCI after fibrinolysis, using stents and contemporary pharmacotherapy, has not been studied in a large adequately powered randomized trial. To compare a pharmacoinvasive strategy of transfer for routine PCI within 6 hours after fibrinolysis with standard treatment after fibrinolysis (including predefined criteria for rescue PCI and delayed cardiac catheterization for patients who do not require rescue PCI). A total of 1200 patients with high-risk ST-elevation myocardial infarction presenting to non-PCI centers will be randomized to a pharmacoinvasive strategy (transfer for routine PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis. The primary end point is the 30-day composite of death, reinfarction, recurrent ischemia, heart failure, or shock. More than 900 patients have been enrolled as of April 2007. An interim safety analysis of the first 536 patients demonstrated no safety concerns. Enrolment is expected to be completed in late 2007. This study will provide important data on whether routine early PCI within 6 hours after fibrinolysis is safe and superior to the standard treatment of fibrinolysis with rescue PCI or delayed cardiac catheterization.

Transfer for urgent percutaneous coronary intervention early after thrombolysis for ST-elevation myocardial infarction: The TRANSFER-AMI pilot feasibility study

Most hospitals in Canada do not have percutaneous coronary intervention (PCI) facilities and use thrombolysis as reperfusion therapy for ST-elevation myocardial infarction (STEMI). Urgent PCI after thrombolysis may optimize reperfusion and prevent reinfarction and recurrent ischemia. To determine the feasibility of transferring high-risk STEMI patients from community hospitals in Ontario to PCI centres for urgent PCI within 6 h of thrombolysis. Patients with anterior or high-risk inferior STEMI received tenecteplase and were urgently transferred to PCI centres. PCI was performed if at least 70% stenosis was present in the infarct-related artery, regardless of flow, using coronary stents. Transfer of stable patients back to community hospitals was encouraged 24 h to 48 h after PCI. Eighteen patients were transferred and underwent PCI a median of 3.9 h (range 2.7 h to 6.4 h) after thrombolysis. No complications occurred during transfer. One death occurred that was related to failed reperfusion and cardiogenic shock. Minor access-site bleeding occurred in five patients. Fifteen patients were transferred back to their community hospitals within 24 h of PCI. There were no further deaths or reinfarctions at one-year follow-up. Transfer of high-risk STEMI patients for urgent PCI within 6 h after thrombolysis appears feasible. The randomized trial phase of the Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) will compare this strategy with standard treatment after thrombolysis.