ATOLL seen as supporting enoxaparin over standard heparin in primary PCI

More than two decades into the era of primary PCI, alternatives to unfractionated heparin (UFH) as the procedure's antithrombin adjuvant have been explored far less thoroughly than, say, what form of antiplatelet therapy might be best during the procedure. Now a prospective, randomized trial appears to strengthen observational evidence that the low-molecular-weight heparin (LMWH) enoxaparin (Lovenox, Sanofi-Aventis) may be superior to the heparin "classic" in PCI for STEMI.

The STEMI Treated With Primary Angioplasty and Intravenous Lovenox or Unfractionated Heparin (ATOLL) study, presented here today at the European Society of Cardiology 2010 Congress, randomized about 900 patients undergoing PCI for acute STEMI to receive either IV enoxaparin or UFH with the procedure. The two groups' subsequent 30-day rates of a complex composite primary end point that included death and major bleeding were not significantly different, although the enoxaparin group showed a favorable trend. Also, the LMWH roundly outperformed UFH for most of the trial's prospectively defined secondary end points, which generally were composites of serious clinical events.

That was a big reason the trial's investigators as well experts who spoke, see ATOLL as supporting IV enoxaparin over the traditional primary-PCI mainstay UFH, despite the "missed" primary end point. But even if the drugs were equal clinically and in terms of safety, inherent advantages of enoxaparin over UFH include bolus dosing and no need for measuring coagulation times.

ATOLL was also a reliable test of enoxaparin because the trial entered an especially high-risk primary PCI population, one that closely reflected the kind of patients treated in the "real world," Dr Gilles Montalescot (Hôpital Pitié-Salpêtrière, Paris, France) said. "We included patients in shock, in cardiac arrest. We had no age limit."

When formally presenting ATOLL at the meeting, Montalescot observed that PCI was performed with radial-artery access in two-thirds of cases. Radial access, which has yet to catch on in the US but is common in Europe, poses a much smaller risk of access-site bleeding compared with femoral-artery access. "That's probably why the [difference in the] primary end point wasn't significant," he said.

As the featured discussant following the ATOLL presentation, Dr Harvey White(Green Lane Hospital, Auckland, New Zealand) lauded ATOLL as "a contemporary trial—in fact, a supercontemporary trial—in terms of the use of radial access and the high rate of use of evidence-based therapies. They've shown that enoxaparin is safe and may have an important clinically relevant effect on ischemic end points in patients undergoing primary PCI." Still, he cautioned, "it missed its primary end point."

The trial randomized 910 patients undergoing PCI for STEMI at 43 centers in Austria, France, Germany, and the US, who did not receive any previous anticoagulation, to also receive either:

• IV enoxaparin at 0.5 mg/kg, whether or not GP IIb/IIIa inhibitors are used (at physicians' discretion) without coagulation monitoring.
• UFH at 50 to 70 IU/kg with or 70 to 100 IU without GP IIb/IIIa inhibitors, with dosage titrated to coagulation monitoring.

ATOLL: 30-day outcomes, IV enoxaparin vs unfractionated heparin in primary PCI 

End point	UFH(n=460), %	Enoxaparin (n=450), %	RR reduction,%	p
Death/MI complications*/procedural failure/major bleeding (primary clinical end point)	33.7	28.0	17	0.07
Death/recurrent MI or ACS/urgent revascularization	11.3	6.7	41	0.01
Death/MI complications*	12.4	7.8	37	0.02
Death/recurrent MI/urgent revascularization	8.5	5.1	40	0.04
Non-CABG major bleeding (primary safety end point)	4.9	4.5		NS
Death/MI complications*/major bleeding (net clinical benefit)	15	10.2	32	0.03

*MI complications=Death, resuscitated cardiac arrest, recurrent MI or ACS, urgent revascularization, stroke, peripheral/pulmonary embolism

The relative risk of death from any cause was 40% lower (p=0.08) and the composite rate of death or resuscitated cardiac arrest fell 42% (p<0.05) in the enoxaparin group compared with those who received UFH.