Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction - TRANSFER-AMI

Jun 24, 2009
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Trial Sponsor:
Canadian Institutes of Health Research; Hoffman La Roche, Canada; and Abbott Vascular Canada
Date Presented:
01/01/2008
Date Published:
01/01/2009
Date Updated:
06/24/2009
Original Posted Date:
06/24/2009
References

Description:

The goal of this trial was to evaluate the role of transfer for routine percutaneous coronary intervention (PCI) within 6 hours after fibrinolysis, using contemporary stents and pharmacotherapy, in patients with high-risk ST-elevation myocardial infarction (STEMI) presenting to centers where primary PCI was not feasible in a timely manner.

Hypothesis:

Routine early PCI within 6 hours after fibrinolysis would be safe and superior to the standard treatment of fibrinolysis with rescue PCI or delayed cardiac catheterization in patients with STEMI who did not undergo primary PCI.

Study Design

Study Design:

Patients Enrolled: 1,059
Mean Follow Up: 30 days
Mean Patient Age: Median age: 56.5 years; age >75 years: 9%
Female: 20

Patient Populations:

  • Patients with STEMI within 12 hours of symptom onset to participating non-PCI centers and treated with TNK
  • ≥2 mm ST-segment elevation in two anterior leads or ≥1 mm ST-segment elevation in two inferior leads, along with at least one of the following:
    • Systolic blood pressure <100 mm Hg,
    • Heart rate >100 bpm,
    • Killip class II-III,
    • ≥2 mm of ST-segment depression in the anterior leads,
    • ≥1 mm of ST elevation in right-sided lead V4 (V4R), indicative of right ventricular involvement

Exclusions:

  • Cardiogenic shock
  • PCI within 1 month
  • Prior cardiac bypass surgery
  • Availability of primary PCI with an anticipated door-to-balloon time of <60 minutes
  • Left bundle branch block
  • Use of thrombolytic agent other than TNK for index event
  • Contraindication to use of thrombolytics, such as recent trauma or surgery
  • History of heparin-induced thrombocytopenia
  • Documented allergy to aspirin
  • Other serious illness (e.g., active cancer, significant hepatic disease)
  • Serum creatinine >1.4 mg/dl
  • Use of low molecular weight heparin in the last 12 hours in patients >75 years of age

Primary Endpoints:

  • Thirty-day composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, and cardiogenic shock

Secondary Endpoints:

  • Death or reinfarction at 6 months
  • TIMI/GUSTO severe bleeding

Drug/Procedures Used:

Patients with STEMI were randomized to a pharmacoinvasive strategy (emergent transfer for PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis (which included rescue PCI as required for ongoing chest pain and <50% resolution of ST-elevation at 60-90 minutes, or if patients were hemodynamically unstable).

For standard treatment patients who did not require rescue PCI, elective cardiac catheterization within the first 2 weeks was encouraged, but not mandated. All patients received standard-dose tenecteplase (TNK), heparin, and aspirin 160-325 mg.

Concomitant Medications:

Either unfractionated heparin (UFH) or enoxaparin was used based on institutions' standard practice, using weight-adjusted dosing consistent with published STEMI guidelines. Clopidogrel loading (300 mg for patients ≤75 years of age, and 75 mg if >75 years of age) was strongly encouraged in all study patients. Glycoprotein IIb/IIIa inhibitors were used at the interventional centers (not at the site of fibrinolysis), as per the discretion of the operator.

PCI of the culprit lesion was performed if ≥70% stenosis, or high-risk features were present (i.e., thrombus, ulceration, dissection). Stents were used whenever technically feasible (bare-metal: 79.3%).

Other medications: beta-blockers (87%), statins (90%), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (81.5%)

Principal Findings:

A total of 1,059 patients were randomized, 537 to the pharmacoinvasive arm, and 522 to the standard treatment arm. About 54% of patients had anterior ST elevations on the electrocardiogram. Cardiac catheterization was performed in 98.5% of patients in the pharmacoinvasive arm, and 88.7% of patients in the standard treatment arm. The median time to administration of TNK from onset of symptoms was about 2 hours in both arms, whereas the median time from TNK to catheterization was 2.8 hours in the pharmacoinvasive arm, and 32.5 hours in the standard treatment arm. PCI was performed in 84.9% of the patients in the pharmacoinvasive arm, and 67.4% in the standard therapy arm. An urgent catheterization was necessary in 34.9% of the patients in the standard therapy arm. Radial access was employed in 17% of the patients.

The infarct-related vessel was the left anterior descending artery in about 50% of the patients. Baseline TIMI flow after TNK was grade 2/3 in 70.4% and 69.5%, respectively.

The incidence of the primary endpoint of death, MI, heart failure, severe recurrent ischemia, or shock was significantly lower in the pharmacoinvasive arm (11.0%) compared with the standard management arm (17.2%) (hazard ratio 0.64, 95% confidence interval 0.47-0.87, p = 0.004). The incidence of mortality, reinfarction, recurrent ischemia, heart failure, and cardiogenic shock was 4.5% and 3.4% (p = 0.39), 3.4% and 5.7% (p = 0.06), 0.2% and 2.1% (p = 0.003), 3.0% and 5.6% (p = 0.04), and 4.5% and 3.1% (p = 0.23) in the pharmacoinvasive and conventional treatment arms, respectively. Death or MI was similar between the two arms at 6 months (8.9% vs. 10.6%, p = 0.36).

Any bleeding tended to be higher in the pharmacoinvasive arm (20.5% vs. 16.1%, p = 0.06). The incidence of TIMI or GUSTO major bleeding was 7.4% and 9.0%, respectively (p = 0.36). The rates of transfusion were similar.

Interpretation:

The results of this large randomized clinical trial indicate that in patients presenting with STEMI to centers without timely access to a catheterization lab, a pharmacoinvasive approach consisting of full-dose thrombolytics, followed by emergent transfer for cardiac catheterization within 6 hours, is safe and efficacious compared to treatment with thrombolytics and transfer for rescue PCI only. This suggests that transfer to PCI centers should be initiated immediately after fibrinolysis without waiting to see whether reperfusion is successful or not.

The results of this trial are noteworthy, and reinforce current American College of Cardiology/American Heart Association guidelines on this topic. These results differ from those noted in earlier angioplasty trials (such as TIMI II), but confirm similar results noted in smaller trials on this topic (such as CARESS-in-AMI). A pharmacoinvasive strategy, as described here, consisting of full-dose TNK, followed by urgent PCI, with clopidogrel and liberal use of glycoprotein IIb/IIIa inhibitors, should also be differentiated from facilitated PCI, where PCI is routinely performed immediately after full-dose fibrinolysis. The latter has been shown to be associated with a higher rate of adverse outcomes. The optimal timing of PCI following fibrinolysis, based on this and other studies, thus seems to be about 2-17 hours.

References:

Cantor WJ, Fitchett D, Borgundvaag B, et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med 2009;360:2705-18.

Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI). Presented by Dr. Warren Cantor at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Keywords: Pyridinolcarbamate, Cardiac Catheterization, Heparin, Ticlopidine, Fibrinolytic Agents, Electrocardiography, Angioplasty, Heart Rate, Stents, Percutaneous Coronary Intervention, Shock, Cardiogenic, Chest Pain, Fibrinolysis, Heart Failure, Confidence Intervals, Tissue Plasminogen Activator


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