ArticlesIntravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial
Introduction
Anticoagulation during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) has traditionally been supported by unfractionated heparin, largely on the basis of evidence extrapolated from studies of elective angioplasty. The Joint STEMI/PCI Guidelines Update1 produced by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions as well as guidelines from the Task Force on Myocardial Revascularization of the European Society of Cardiology2 continue to afford unfractionated heparin a class 1 recommendation for this indication while recognising that evidence is limited (level of evidence C).
In recent studies with new anticoagulants in primary PCI, such as OASIS-6 (Organization for the Assessment of Strategies for Ischemic Syndromes),3 the subgroup undergoing primary PCI had no clinical benefit with the indirect factor Xa inhibitor fondaparinux and had an excess of catheter thrombosis. In the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial,4 the direct thrombin inhibitor bivalirudin alone, as compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors, significantly reduced 30-day rates of major bleeding and mortality, but there was increased stent thrombosis within the first 24 h (not at 30 days; class I-B recommendation). Most noteworthy is that in both studies a large proportion of patients received a full dose of unfractionated heparin before randomisation, precluding a real comparison between two anticoagulant drugs. Therefore, there has thus far been no comparison between two anticoagulants in primary PCI that is not confounded by prerandomisation anticoagulation therapy or differing antiplatelet strategy, which can both affect clinical outcomes.2, 3, 5, 6, 7, 8, 9
Subcutaneous enoxaparin provides more predictable anticoagulation than does unfractionated heparin10 and has an established role in the management of non-ST-elevation acute coronary syndromes and in STEMI treated with thrombolysis.6, 11, 12 The excess bleeding reported in these studies might have been due to the prolonged treatment with therapeutic doses of subcutaneous enoxaparin or the concomitant administration of unfractionated heparin, or both. The clinical usefulness of intravenous enoxaparin has been shown recently in elective PCI at a dose of 0·5 mg/kg, which provides immediately an adequate level of anticoagulation with the short half-life of the drug, adapted to interventional procedures.13, 14, 15, 16, 17 Enoxaparin was also compared with unfractionated heparin in several non-randomised studies that reported significantly better results with enoxaparin in PCI of STEMI,18, 19, 20, 21, 22 but there has been no randomised evaluation of intravenous enoxaparin in primary PCI.
The ATOLL (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) study is a randomised comparison of intravenous enoxaparin and unfractionated heparin in primary PCI, excluding patients who received any anticoagulation before randomisation and requiring no crossover from one drug to the other during or after the procedure.
Section snippets
Participants
ATOLL was an international, randomised, open-label trial evaluating intravenous enoxaparin versus intravenous unfractionated heparin in patients undergoing primary PCI for STEMI. Patients were enrolled at 64 sites in four countries (Austria, France, Germany, USA). Wherever possible, medical teams travelling in mobile intensive care units (ambulances) were regarded as study sites and were allowed to select, randomly assign, and treat patients. STEMI was defined as continuous ischaemic chest pain
Results
Between July, 2008, and January, 2010, 910 patients were randomly assigned to receive enoxaparin (450 patients) or unfractionated heparin (460 patients) before primary PCI. Diagnosis of STEMI, randomisation, and initial treatment were done in the field by the mobile emergency medical service in 643 (71%) cases. Baseline characteristics were well balanced between treatment groups (table 1). Patients were mainly male (n=712, 78%), 165 (18%) were older than 75 years, 86 (9%) had signs of heart
Discussion
The ATOLL trial evaluated the efficacy and safety of intravenous enoxaparin versus unfractionated heparin in the contemporary interventional management of STEMI, which in most patients included prehospital diagnosis and treatment, intense antiplatelet therapy, and radial artery access for thrombus aspiration and primary stenting (panel). In this trial, data suggested fewer primary endpoint events with intravenous enoxaparin 0·5 mg/kg than with heparin, but the difference was not significant
References (30)
- et al.
Adding intravenous unfractionated heparin to standard enoxaparin causes excessive anticoagulation not detected by activated clotting time: results of the STACK-on to ENOXaparin (STACKENOX) study
Am Heart J
(2009) - et al.
A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes
J Am Coll Cardiol
(2006) - et al.
Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial
Lancet
(2009) - et al.
A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention
J Am Coll Cardiol
(2002) - et al.
Enoxaparin anticoagulation monitoring in the catheterization laboratory using a new bedside test
J Am Coll Cardiol
(2010) - et al.
Enoxaparin in primary and facilitated percutaneous coronary intervention: a formal prospective nonrandomized substudy of the FINESSE trial (Facilitated INtervention with Enhanced Reperfusion Speed to Stop Events)
JACC Cardiovasc Interv
(2010) - et al.
The use of intravenous enoxaparin in elective percutaneous coronary intervention in patients with renal impairment: results from the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial
Am Heart J
(2009) - et al.
Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial
J Am Coll Cardiol
(2007) - et al.
Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction (the ARMADA study)
Am J Cardiol
(2003) - et al.
Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial
Lancet
(2011)
ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention)
Circulation
Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)
Eur Heart J
Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial
JAMA
Bivalirudin during primary PCI in acute myocardial infarction
N Engl J Med
Comparison of fondaparinux and enoxaparin in acute coronary syndromes
N Engl J Med
Cited by (247)
Safety and Efficacy of Enoxaparin During Low-Risk Elective Percutaneous Coronary Intervention
2024, American Journal of CardiologyDirect Oral Anticoagulants Affect Activated Clotting Time During and Bleeding Events After Percutaneous Coronary Intervention
2023, American Journal of CardiologyThe Evolution of Anticoagulation for Percutaneous Coronary Intervention: A 40-Year Journey
2022, Canadian Journal of CardiologyReply: Should Postprocedure Anticoagulation Be Routinely Needed in Acute STEMI Patients Undergoing Primary PCI?
2022, JACC: Cardiovascular InterventionsAnticoagulation After Primary PCI: The Land of Promises and Uncertainty
2022, JACC: Cardiovascular Interventions2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
2022, Journal of the American College of Cardiology