Coronary artery diseaseA Direct Comparison of Intravenous Enoxaparin With Unfractionated Heparin in Primary Percutaneous Coronary Intervention (from the ATOLL Trial)
Section snippets
Methods
ATOLL was an international, randomized, open-label trial led by the Academic ACTION study group (www.action-coeur.org) evaluating IV enoxaparin versus IV UFH in patients undergoing primary PCI for ST elevation myocardial infarction. The study protocol has been described in detail elsewhere.1 All patients assigned to enoxaparin by randomization received an IV bolus of 0.5 mg/kg enoxaparin without anticoagulation monitoring as previously described.2 After the procedure, prolongation of
Results
In the ATOLL trial, none of the 910 patients received an anticoagulant before randomization. Compliance with interactive voice response system-indicated study drug before and during catheterization was 96% (n = 433) and 97% (n = 444) for IV enoxaparin and IV UFH, respectively. Patients who were administered both heparins numbered 8 (1.8%) and 6 (1.3%) before and during catheterization, respectively, and 42 (9.3%) and 58 (12.6%) during the whole study period in the enoxaparin and UFH groups.
Discussion
In the ATOLL trial, most patients were treated according to the study protocol.1 Only 1 of 10 patients was crossed to the other study drug during or after revascularization. Crossover to another heparin and simultaneous administration of both anticoagulants were protocol violations and were shown in the past to be associated with worse outcomes.4, 5, 6, 7, 8 Nine of 10 patients were treated consistently with the same anticoagulant, which is a major difference compared with recent trials in
Acknowledgment
The authors are indebted to the patients who agreed to participate in this trial, the study contributors, and the investigators who recruited patients. Prof. Gilles Montalescot had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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Cited by (51)
The Evolution of Anticoagulation for Percutaneous Coronary Intervention: A 40-Year Journey
2022, Canadian Journal of CardiologyCitation Excerpt :At 30 days, a trend toward reduction in the primary net composite (death, complication of MI, procedure failure, or major bleeding) was observed with enoxaparin (HR, 0.83; 95% CI, 0.68-1.01) with no difference in major bleeding among groups.26 In a per-protocol analysis of ATOLL, enoxaparin was superior to UFH in reducing ischemic end points and mortality.27 A subsequent meta-analysis confirmed the lower rates of mortality and bleeding with enoxaparin in STEMI patients undergoing primary PCI.28
Reply: Should Postprocedure Anticoagulation Be Routinely Needed in Acute STEMI Patients Undergoing Primary PCI?
2022, JACC: Cardiovascular Interventions2019 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Guidelines on the Acute Management of ST-Elevation Myocardial Infarction: Focused Update on Regionalization and Reperfusion
2019, Canadian Journal of CardiologyCitation Excerpt :A meta-analysis of 10 studies that compared enoxaparin and UFH in the setting of PPCI for STEMI showed a reduction in mortality (RR,0.51; 95% CI, 0.41-0.61) and major bleeding (RR, 0.68; 95% CI, 0.49-0.94) with enoxaparin; this benefit was more pronounced in STEMI patients with higher risk.194 The 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) trial randomized STEMI patients to a 0.5 mg/kg I.V. dose of enoxaparin or UFH in the setting of primary PCI.195,196 Although the study failed to meet its combined primary end point (death, MI, procedural failure, and major bleeding at 30 days; 28% with enoxaparin vs 34% with UFH P = 0.06), enoxaparin was superior to UFH in reducing the main secondary end point of death, MI, or major bleeding (7% vs 11%; P = 0.015 and other clinically significant ischemic end points).195,196
Reperfusion therapies for acute ST elevation myocardial infarction
2018, Cardiac Intensive CarePre-hospital ticagrelor in ST-segment elevation myocardial infarction in the French ATLANTIC population
2017, International Journal of CardiologyCitation Excerpt :Lastly, in the French population, radial access and younger age were independently associated with a reduced rate of ischaemic complications, major bleeding complications and mortality. The high rate of use of enoxaparin in the present ATLANTIC substudy is supported by the results of the randomized ATOLL trial [3], together with the ATOLL per-protocol analysis [8] and a meta-analysis of 23 trials [4], both of which favour IV enoxaparin vs IV unfractionated heparin in terms of a reduction in ischaemic and bleeding events. In line with our observations, the recent European guidelines consider that enoxaparin is an alternative to unfractionated heparin in primary PCI [9].
Anticoagulation in Acute Coronary Syndrome-State of the Art
2018, Progress in Cardiovascular DiseasesCitation Excerpt :Enoxaparin also provided a 40% reduction on the secondary composite endpoints of death, recurrence and complication of MI (RR = 0.59, 95% [0.38–0.91], p = .015). Head to head per-protocol analysis found that the primary endpoint, the mortality rate and the bleeding events were reduced in the enoxaparin group18 (RR = 0.76 95%CI [0.62–0.94], p = .012). These findings were confirmed by other randomized controlled trials, where enoxaparin administration was associated with a reduced rate of death and re-infarction without an increased rate of bleeding events19–20 (Fig. 1a and b).
This study was conducted by the ACTION study group (www.action-coeur.org) and AP-HP with a grant from Sanofi-Aventis.
The ATOLL trial is registered at clinicaltrials.gov (NCT00718471).
See page 1371 for disclosure information.