Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction - CARESS-in-AMI: 30-Day and 1-Year Results

Description:

The goal of the trial was to evaluate immediate transfer for urgent percutaneous coronary intervention (PCI) or standard therapy and rescue PCI if needed among ST-elevation myocardial infarction (STEMI) patients admitted to centers without PCI facilities who were initially treated with heparin, half-dose reteplase, and abciximab.

Hypothesis:

Among high-risk STEMI patients presenting to a center without PCI facilities who receive heparin, half-dose reteplase, and abciximab, immediate transfer for urgent PCI would reduce major adverse cardiac events compared with standard therapy and rescue PCI if needed.

Study Design

  • Randomized
  • Parallel

Patients Screened: 600
Patients Enrolled: 600
Mean Follow Up: 30 days
Mean Patient Age: 60 years
Female: 22%
Mean Ejection Fraction: 45%

Patient Populations:

STEMI patients presenting within 12 hours from symptom onset with one or more of the following high-risk criteria: summation of ST-segment elevation ≥15 mm in all 12 ECG leads, new left bundle branch block, previous MI, Killip class II or III, and left ventricular ejection fraction <35%>

Exclusions:

  • Previous coronary artery bypass grafting or PCI
  • Cardiogenic shock
  • Need for concomitant major surgery
  • Severe chronic renal or hepatic impairment
  • MI within the previous 2 weeks
  • Contraindications to thrombolytic therapy, abciximab, aspirin, or clopidogrel

Primary Endpoints:

Composite endpoint of death, reinfarction, or refractory ischemia at 30 days

Secondary Endpoints:

  • Individual components of the primary outcome
  • Composite endpoint of death, reinfarction, or refractory ischemia at 1 year

Drug/Procedures Used:

Patients admitted to hospitals without PCI capabilities and who were treated initially with heparin, half-dose reteplase, and abciximab were randomized to immediate transfer for urgent PCI (n = 299) or standard therapy and rescue PCI if needed (n = 301).

Concomitant Medications:

For the two groups at baseline&mdash;immediate transfer versus standard therapy/rescue PCI&mdash;aspirin 17% versus 22%, statins 10% versus 17%, and beta-blocker 13% versus 18%. In the standard therapy and rescue PCI if needed group, heparin was administered for 24 hours. At discharge, the use of aspirin was 99% versus 94% and clopidogrel was 86% versus 57%.

Principal Findings:

The median time from symptom onset to reteplase administration was 165 minutes in the immediate PCI group and 161 minutes in the standard care and rescue PCI group; 86% of the immediate PCI group underwent PCI, whereas 30% of the standard care group received rescue PCI. The median time from thrombolysis until PCI was 135 minutes in the immediate PCI group and 211 minutes in the standard therapy group.

The primary endpoint of death, reinfarction, or refractory ischemia at 30 days occurred less frequently in the immediate PCI group (4.4% vs. 10.7%, p = 0.005), driven by a reduction in refractory ischemia (0.3% vs. 4.0%, p = 0.003). Reinfarction rates were 1.3% versus 2.0% (p = 0.75), death rates were 3.0% versus 4.7% (p = 0.40), and stroke rates were 0.7% versus 1.3% (p = 0.50). Major bleeding occurred in 3.4% versus 2.3% (p = 0.47).

At 1 year, At 1 year, the primary endpoint of death, reinfarction, or refractory ischemia occurred in 11.4% of the immediate PCI group versus 16.4% of the standard therapy group (p = 0.07). Recurrent PCI occurred less frequently in the transfer group (14.4% vs. 42.4%, p < 0.0001), whereas death was 6.4% vs. 5.7% (p = 0.73), respectively.

Interpretation:

Among STEMI patients admitted to centers without PCI facilities initially treated with heparin, half-dose reteplase, and abciximab, immediate transfer for PCI was associated with a reduction in the primary endpoint of death, MI, or refractory ischemia at 30 days compared with continued medical management with revascularization only performed for rescue PCI. Benefit was still seen from lysis and transfer, although less robust at 1 year. There was no apparent increase in major bleeding or stroke from immediate transfer for PCI.

A meta-analysis of trials that compared facilitated PCI with primary PCI revealed that primary PCI is the preferred strategy when PCI facilities are readily available. In fact, facilitated PCI appears harmful, with increased bleeding, stroke, and death. A primary difference in these approaches is that facilitated PCI involves immediate PCI after lysis, whereas in the current study, transportation delayed this time by approximately 2 hours. A limitation of the current study is that there was no primary PCI control arm.

Unfortunately, most patients who experience STEMI do not receive angioplasty within the 90-minute, guideline-recommended time frame. The present study suggests that for high-risk STEMI patients younger than 75 years of age who present to a facility without PCI capabilities, an approach of aspirin, heparin, half-dose reteplase, and abciximab followed by immediate transfer for PCI may be superior to standard care and rescue PCI if needed.

References:

Di Mario C, Dudek D, Piscione F, et al. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial. Lancet 2008;371:559-68.

One-Year Results of the Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI) Trial. Presented by Dr. Krzysztof Zmudka at the European Society of Cardiology Congress, August/September 2008, Munich, Germany.

Presented by Dr. Carlo Di Mario at the European Society of Cardiology Congress, September 2007, Vienna, Austria.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, EP Basic Science, Lipid Metabolism

Keywords: Stroke, Myocardial Infarction, Heparin, Immunoglobulin Fab Fragments, Electrocardiography, Angioplasty, Percutaneous Coronary Intervention, Recombinant Proteins, Bundle-Branch Block, Stroke Volume, Tissue Plasminogen Activator


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