Antiplatelet Therapy Alone Versus Lovenox Plus Antiplatelet Therapy in Patients at Increased Risk of Stent Thrombosis - ATLAST


ATLAST was a multicenter, double-blinded, placebo-controlled, randomized clinical trial assessing the efficacy and safety of 14 days of enoxaparin therapy following coronary artery stenting.


Treatment with enoxaparin in addition to aspirin and ticlopidine would be associated with a reduction in 30-day death, myocardial infarction (MI), and urgent coronary artery revascularization (an endpoint designed to detect cases of subacute stent thrombosis).

Study Design

Study Design:

Patients Enrolled: 1,102
Mean Follow Up: 30 days
Mean Patient Age: Mean 60 years
Female: 25
Mean Ejection Fraction: Mean 51%

Patient Populations:

Any of the following: acute MI <48 hours before stenting; abrupt closure with TIMI grade 0 or 1 flow; threatened abrupt closure (TIMI grade 2 flow or angina with significant residual dissection in a target vessel <3.0 mm) before stenting; ejection fraction <35%; total occlusion of target vessel <7 days; stenting of a degenerated saphenous vein graft <4 mm in diameter with diffuse distal vessel disease; placement of a 2.5 mm diameter stent in a vessel ≤2.5 mm; placement of ≥1 stents in a true bifurcation lesion; or any of the following by angiography or ultrasound: intracoronary thrombus, diffuse distal disease, persistent filling defect within the stent, persistent dissection at the stent margin, or suboptimal stent deployment based on residual angiographic stenosis >20% or incomplete stent apposition by ultrasound


Contraindication to anticoagulation; uncontrolled hypertension; hemoglobin <9 mg/dl; platelet count <100,000/mm3; glycoprotein IIb/IIIa inhibitor or dipyridamole therapy within <72 hours; thrombolysis <6 hours; planned coronary artery bypass graft or PCI within 30 days; other indications for anticoagulation; groin hematoma at sheath site >5 cm after stenting; allergy or intolerance to aspirin, ticlopidine, heparin, or any low molecular weight heparin; prior heparin-associated thrombocytopenia; pork allergy; unwillingness or inability to give or receive subcutaneous injections; or serious noncardiac illness

Primary Endpoints:

Composite of all-cause mortality, nonfatal MI, or urgent revascularization at 30 days. Only MIs that were deemed to have occurred after study drug initiation (thus in general excluding periprocedural MIs) were counted in the primary efficacy analysis.

Secondary Endpoints:

Incidence of the composite endpoint at 14 days, death or MI at 14 and 30 days, adverse events, major bleeding, minor bleeding, and thrombocytopenia (platelet count <100,000/mm3)

Drug/Procedures Used:

Stents were implanted in the standard manner according to local practice. Vascular access sheaths were removed ≥4 hours after procedural unfractionated heparin (UFH). At vascular sheath removal, patients were randomized to receive subcutaneous enoxaparin twice daily (40 mg for patients <65 kg, 60 mg for patients >65 kg) or matching placebo for 14 days. The first injection of the study drug was given ≥2 hours after sheath removal and 4-10 hours after the last dose of UFH.

Concomitant Medications:

Aspirin 325 mg/day, starting on or before the day of stenting and continuing for ≥6 months. Ticlopidine 250 mg twice daily for 14 days, beginning ≤72 hours before stenting. “Loading” doses of aspirin (650 mg) and ticlopidine (500 mg) were recommended for patients not already taking either drug.

Principal Findings:

A total of 1,102 patients were randomized. Overall, the two study groups were well-matched, with approximately 45% of patients undergoing percutaneous coronary intervention (PCI) for an MI. The average stent size was 3.2 mm and the average stent length was 18 mm.

The overall incidence of the primary endpoint of death, MI (only MIs occurring after study drug administration were included), or urgent revascularization at 30 days was 2.3%. Although numerically less frequent among enoxaparin-treated patients, the incidence of the primary endpoint was not significantly different between the two study arms (1.8% vs. 2.7%, p=0.30). The 30-day rate of MI was significantly lower among enoxaparin-treated patients (0.4% vs. 1.6%, p=0.04), and the composite of MI or urgent revascularization trended lower among enoxaparin-treated patients (0.9% vs. 2.2%, p=0.08).

Bleeding events were more common among enoxaparin-treated patients (28% vs. 6.7%, p<0.001), particularly driven by a far greater incidence of minor bleeding (25% vs. 5.1%, p<0.001) and a trend toward more major bleeding (3.3% vs. 1.6%, p=0.08). Enoxaparin was more often discontinued early (24% vs. 13%, p<0.001).


In this multicenter, randomized, controlled trial of 14 days of enoxaparin versus placebo given in addition to aspirin and ticlopidine among high-risk patients after coronary stenting, treatment with enoxaparin was associated with favorable outcomes with respect to ischemic endpoints, but at the expense of increased bleeding. The overall rates of death, MI, or urgent target vessel revascularization were quite low in both arms in this relatively high-risk patient cohort. This was partly due to the design of the study, which only included MIs occurring after study drug initiation (excluding periprocedural MIs).

The study was originally designed to enroll 2,000 patients; however, an interim analysis suggested that the overall event rate (for the combined ischemic endpoint) was too low, and that a sample size of >3,500 patients would be needed to maintain the power to detect a difference between the two study arms. Due to the difficulties enrolling patients and other considerations, the study was terminated early.

Due to the reduced sample size, it is difficult to be confident that the reduction in rates of MI seen among the enoxaparin-treated patients is a robust finding, and not due to chance alone. Nonetheless, the study does appear to be adequately powered with respect to the observed differences in bleeding endpoints, which occurred at a significantly greater frequency among enoxaparin-treated patients.


Batchelor WB, Mahaffey KW, Berger PB, et al. A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial. J Am Coll Cardiol 2001;38:1608-13.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Heparin, Ticlopidine, Constriction, Pathologic, Percutaneous Coronary Intervention, Stents, Thrombosis, Enoxaparin, Saphenous Vein

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