Major Finding: The prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH.
Data Source: Prospective, active-control arm Phase III trial involving 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries randomized to enoxaparin (0.5 mg/kg) or 50-70 IU/kg UFH (with a glycoprotein IIb/IIIa inhibitor) or 70-100 IU/kg without.
Disclosures: The study was sponsored by Assistance Publique-Hôpitaux de Paris with the help of a research grant from Sanofi-Aventis. Dr. Montalescot disclosed that he has received consulting and/or lecture fees from Sanofi-Aventis as well as more than a dozen others.
STOCKHOLM — Intravenous enoxaparin outperformed conventional unfractionated heparin for anticoagulation in primary percutaneous coronary intervention for ST-elevation MI in the Phase III randomized ATOLL trial.
“This is the first pure, direct head-to-head comparison between two anticoagulants in primary PCI [percutaneous coronary intervention] with no mixing of drugs at any point. Our data demonstrate that enoxaparin, which is easier to use, reduced all serious ischemic events on top of intense antiplatelet therapy. And there was no price to pay on the safety side for the benefit observed on the ischemic side,” Dr. Gilles Montalescot said in presenting the ATOLL data at the meeting.
The ATOLL (Acute STEMI Treated With Primary Angioplasty and Intravenous Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up) trial included 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries. None of the patients had received any anticoagulant before randomization. Two-thirds of the participants underwent cardiac catheterization using radial artery access.
During randomization, half of the participants received intravenous enoxaparin at 0.5 mg/kg regardless of whether or not they were on a glycoprotein IIb/IIIa inhibitor.
The other half got intravenous unfractionated heparin (UFH) at either 50-70 IU/kg if they received a glycoprotein IIb/IIIa inhibitor, or 70-100 IU/kg if they did not. UFH dosing was adjusted based on activated clotting time (ACT) measurements; enoxaparin dosing was not.
The primary study end point – a 30-day composite of death, procedure failure, complications of myocardial infarction, or non-CABG major bleeding – occurred in 33.7% of the UFH group, compared with 28% on enoxaparin. The resultant 17% relative risk reduction favoring the low-molecular-weight heparin fell just shy of statistical significance, probably because the exceptionally high use of radial artery access.
However, hard ischemic secondary end points were markedly reduced with enoxaparin. For example, the prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH, said Dr. Montalescot, professor of medicine and head of the cardiac care unit at Hôpital Pitié-Salpêtrière, Paris.
Similarly, the classic triple ischemic end point comprised of death, reinfarction, or urgent revascularization was 8.5% in the UFH arm, compared with 5.1% with enoxaparin. The end point of death or complications of MI occurred in 12.4% of the UFH group, compared with 7.8% with enoxaparin, a 37% reduction in risk.
The primary safety end point in ATOLL – in-hospital major bleeding – occurred in 4.5% of patients on UFH and similarly in 4.9% of those on enoxaparin. The combined rate of major bleeding, complications of MI, or death occurred in 15% of the UFH group, compared with 10.2% on enoxaparin, a statistically significant difference.
Many American interventional cardiologists like using UFH because they can monitor ACT and bump up the heparin in the event of a low-flow state after stent deployment. Dr. Montalescot commented that it makes sense to check ACTs in using UFH because the anticoagulation provided by UFH is “totally unpredictable.” But several studies have shown that staying within the ACT targets doesn't have any impact on ischemic event rates.
“Also, enoxaparin's anticoagulant capability is very predictable. It has been measured in many studies, and we get 95% of patients within the target range. So it doesn't make sense, really, to control anticoagulation in the cath lab. We don't have the ability to adjust anticoagulation with enoxaparin, but you'll get almost all your patients to target with the IV injection,” he explained.
American observers were duly impressed.
“Enoxaparin probably merits more attention in the acute care setting than it receives,” hotline session cochair Dr. Clyde Yancy said in an interview.
“[It] hasn't been broadly embraced by the cardiovascular community, but it looks like there are some real clinical advantages. These new data as well as some older data suggest we should pay more attention to enoxaparin than we have,” added Dr. Yancy, immediate past president of the American Heart Association and medical director of the Baylor Heart and Vascular Institute, Dallas.