Analysis Strengthens Support for Enoxaparin Over Heparin in PCI for STEMI

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A per-protocol analysis from the ATOLL trial suggests that enoxaparin is superior to unfractionated heparin in reducing ischemic endpoints and mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The study was published online September 9, 2013, ahead of print in the American Journal of Cardiology.

For the ATOLL trial, Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière (Paris, France), and colleagues randomly assigned 910 STEMI patients undergoing primary PCI to receive either intravenous enoxaparin (0.5 mg/kg) or unfractionated heparin (50-70 IU with GPIs and 70-100 IU without; dose adjusted to activated clotting time). After PCI, patients continued on their medication.

The primary analysis showed a nonsignificant 17% reduction in the likelihood of the study's primary endpoint (composite of 30-day all-cause mortality, 30-day MI complications, procedural failure, and non-CABG major bleeding requiring hospitalization) with enoxaparin compared with heparin. But the rate of the main secondary endpoint (all-cause mortality, recurrent ACS, or urgent revascularization within 30 days) was 41% lower with enoxaparin.

Enoxaparin Proves Superior

For the prespecified per-protocol analysis, researchers excluded 115 patients who did not receive the treatment allocated by randomization, or who were switched to another anticoagulant after PCI.

Among these 795 patients (87.4%), rates of the primary endpoint and the main secondary endpoint both were lower with enoxaparin. Patients treated with enoxaparin also had less major bleeding and lower mortality than those in the heparin group. Importantly, death or MI, as well as the net clinical benefit, also were reduced in the enoxaparin group compared with heparin (table 1).

Table 1. Clinical Outcomes


(n = 400)

Unfractionated Heparin
(n = 395)

RR (95% CI)

P Value

Primary Endpoint



0.76 (0.62-0.94)


Main Secondary Endpoint



0.37 (0.22-0.63)

< 0.0001

Major Bleeding



0.46 (0.21-1.01)


Major or Minor Bleeding



0.65 (0.43-1.00)





0.36 (0.18-0.74)


Death or MI



0.44 (0.27-0.7)


Net Clinical Benefit



0.46 (0.3-0.7)


Support for Anticoagulant Options

According to the study authors, the per-protocol findings “globally confirm the results of the main publication that showed significant reductions of ischemic events, a significant reduction of death or resuscitated cardiac death, and favorable trends on safety endpoints despite a 70% radial access rate that dampened the incidence of bleeding complications.”

Furthermore, Dr. Montalescot and colleagues say the findings also provide support for recently published European Society of Cardiology STEMI guidelines recognizing 2 anticoagulant options as preferable to heparin in primary PCI. While bivalirudin is the preferred strategy over the combination of heparin and GPIs, enoxaparin is also recommended based on the ATOLL trial and other studies showing benefit with enoxaparin on both ischemic and bleeding events, they add.

“The present per-protocol analysis of the ATOLL trial confirms further these data when the drug is properly used without switching with [unfractionated heparin],” they note.


Collet J-P, Huber K, Cohen M, et al. A direct comparison of intravenous enoxaparin with unfractionated heparin in primary percutaneous coronary intervention (from the ATOLL trial). Am J Cardiol. 2013;Epub ahead of print.



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  • Dr. Montalescot reports receiving research grants and consulting fees from numerous pharmaceutical companies.

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