Acute Myocardial Infarction Treated With Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up - ATOLL


The goal of the trial was to evaluate treatment with enoxaparin compared with unfractionated heparin (UFH) among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).


Enoxaparin will be more effective in reducing ischemic and bleeding events.

Study Design

  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • STEMI patients

    Number of enrollees: 910
    Duration of follow-up: 30 days
    Mean patient age: median 59 years
    Percentage female: 22%


  • Use of antithrombin or lytic therapy prior to randomization
  • Limited life expectancy
  • Childbearing potential
  • Contraindication to aspirin, thienopyridine, or heparin

Primary Endpoints:

  • All-cause death, complications of MI, procedural failure, or non-CABG major bleeding
  • Complications of MI defined as resuscitated cardiac arrest, recurrent MI, urgent revascularization, stroke, peripheral or pulmonary embolism
  • Procedural failure defined as stent thrombosis, bailout use of glycoprotein IIb/IIIa inhibitor, non-TIMI 3 flow post-PCI, ST-resolution <50% post-PCI
  • Major bleeding according to STEEPLE definition

Secondary Endpoints:

  • All-cause death, recurrent MI, or urgent revascularization
  • Non-CABG major bleeding
  • Death or complications of MI
  • Death or resuscitated cardiac arrest
  • Major or minor bleeding
  • Death, complications of MI, or major bleeding

Drug/Procedures Used:

Prior to primary PCI (coronary angiography), STEMI patients were randomized to open-label enoxaparin 0.5 mg/kg intravenous (n = 450) versus UFH 70-100 U/kg (n = 460). The use of a glycoprotein inhibitor was left to operator discretion, and when used, the recommended dose of UFH was lowered to 50-70 U/kg. There was no dose adjustment of enoxaparin with renal dysfunction.

Concomitant Medications:

In the enoxaparin group, during hospitalization, the use of aspirin was 96%, clopidogrel 94%, beta-blocker 88%, angiotensin-converting enzyme inhibitor 75%, and statin 87%.

Principal Findings:

Overall, 910 patients were randomized. In the enoxaparin group, the median age was 59 years, 22% were women, diabetics were 14%, shock and/or cardiac arrest prior to procedure was 5%, median time from symptom onset to randomization was 2.6 hours, radial access was used in 69%, stenting was performed in 96%, thrombus aspiration was performed in 46%, and glycoprotein inhibitor was used in 77%.

The primary outcome, all-cause death, complications of MI, procedural failure, or noncoronary artery bypass graft (CABG) major bleeding occurred in 28% of the enoxaparin group versus 34% of the UFH group (p = 0.063).

For secondary outcomes: death, MI, or revascularization occurred in 5.1% versus 8.5% (p = 0.044); death, complications of MI, or major bleeding occurred in 10.2% versus 15.0% (p = 0.030); death or complications of myocardial infarction occurred in 7.8% versus 12.4% (p = 0.021); all-cause mortality occurred in 3.8% versus 6.3% (p = 0.082); and death or recurrent MI occurred in 4% versus 7% (p = 0.10).

Non-CABG major bleeding occurred in 4.5% versus 4.9% (p = 0.79), and major or minor bleeding occurred in 11% versus 12% (p = 0.65).


Among patients with STEMI, the use of enoxaparin compared with UFH during primary PCI is feasible. Currently, there are relatively limited data to support the use of low molecular weight heparin during primary PCI. Enoxaparin did not reduce the primary outcome, although secondary ischemic outcomes were reduced, and bleeding was similar between the groups.

The elimination half-life of intravenous enoxaparin is 1 to 2 hours, which is significantly shorter than the subcutaneous route. Strength of the trial is that no patients received anticoagulation prior to randomization, thus enabling a clear comparison between study drugs. This trial studied an unusual primary outcome, which consisted of 12 individual components. The benefit seen in secondary outcomes will need to be explored in future larger studies with more standardized definitions of composite ischemic and bleeding events.


Montalescot G, Zeymer U, Silvain J, et al. Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial. Lancet 2011;378:693-703.

Presented by Dr. Gilles Montalescot at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Follow-Up Studies, Heparin, Low-Molecular-Weight, Heart Arrest, Percutaneous Coronary Intervention, Coronary Angiography, Half-Life, Thrombosis, Enoxaparin, Diabetes Mellitus, Hemorrhage

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