Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study

doi:10.1016/S0002-8703(03)00165-0

American Heart Journal

Volume 146, Issue 4, October 2003, Pages 628-634

https://doi.org/10.1016/S0002-8703(03)00165-0 Get rights and content

Abstract

Background

In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI).

Methods

The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST–elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia.

Results

A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively).

Conclusions

The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.

Section snippets

Study design and patient selection

NICE-3 was a prospective, open-label, nonrandomized, observational study conducted at 56 clinical sites in the United States and Canada. Study enrollment took place between January and May 2000. Institutional review boards at each facility approved the protocol; written informed consent was obtained from all patients before enrollment.

Eligible patients had a history of unprovoked chest pain lasting at least 20 minutes within the previous 24 hours, and coronary artery disease (CAD) documented by

Results

A total of 707 patients aged ≥18 years were enrolled in the study; 671 patients received at least 1 dose of enoxaparin and had source-document validation of their clinical outcomes. Of these, 229 (34.1%) received the GP IIb/IIIa antagonist tirofiban, 272 (40.5%) received eptifibatide, and 127 (18.9%) received abciximab. Thus, 628 of 671 patients (93.6%) received combined therapy with enoxaparin and a GP IIb/IIIa antagonist, while 43 patients (6.4%) received enoxaparin alone because planned use

Discussion

LMWHs offer several theoretical advantages over UFH: greater ease of administration, longer half-life, greater bioavailability, less protein binding, and a more predictable degree of anticoagulation without the need for close laboratory monitoring and adjustment.²⁰ LMWHs are also less likely to activate platelets, are less susceptible to inactivation by platelet factor 4, and are associated with a lower risk of heparin-induced thrombocytopenia.20, 21

These advantages, coupled with evidence

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Citation Excerpt :
Twenty-two studies demonstrated improved combined end points (death, MI, revascularization) with an increase in the proportion of patients with bleeding complications when enoxaparin was administered in-hospital rather than UFH in patients with AMI (LOE 1310–320; LOE 2321–326; LOE 5327–329). Four RCTs (LOE 1),330–332,333 three meta-analyses (LOE 1),334–336 six nonrandomised control trials (LOE 2–4),337–344 and five additional studies (LOE 4–5)345–349 did not demonstrate a difference for outcomes among in-hospital patients given enoxaparin compared with UFH. One RCT (LOE 1),350 three nonrandomised control studies (LOE 2),351–353 and two additional studies (LOE 5)354,355 demonstrated improved combined end points (death, MI, revascularization) without increased bleeding when fondaparinux, compared with UFH, was administered in-hospital in patients with AMI.
Antithrombotics in Acute Coronary Syndromes
2009, Journal of the American College of Cardiology
Antithrombotic agents are an integral component of the medical regimens and interventional strategies currently recommended to reduce thrombotic complications in patients with acute coronary syndromes (ACS). Despite great advances with these therapies, associated high risks for thrombosis and hemorrhage remain as the result of complex interactions involving patient comorbidities, drug combinations, multifaceted dosing adjustments, and the intricacies of the care environment. As such, the optimal combinations of antithrombotic therapies, their timing, and appropriate targeted subgroups remain the focus of intense research. During the last several years a number of new antithrombotic treatments have been introduced, and new data regarding established therapies have come to light. Although treatment guidelines include the most current available data, subsequent findings can be challenging to integrate. This challenge is compounded by the complexity associated with different efficacy and safety measures and the variability in study populations, presenting syndromes, physician, and patient preferences. In this work we review recent data regarding clinically available antiplatelet and anticoagulation agents used in the treatment of patients with ACS. We address issues including relative efficacy, safety, and timing of therapies with respect to conservative and invasive treatment strategies. In specific cases we will highlight remaining questions and controversies and ongoing trials, which will hopefully shed light in these areas. In addition to reviewing existing agents, we take a look forward at the most promising new antithrombotics currently in late-stage clinical development and their potential role in the context of ACS management.

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¹: Guest Editor for this manuscript was David A. Vorchheimer, MD, Mount Sinai Medical Center, New York, NY.

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Clinical investigation: acute ischemic heart diseaseCombining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study1

Abstract

Background

Methods

Results

Conclusions

Section snippets

Study design and patient selection

Results

Discussion

J Am Coll Cardiol

Am Heart J

Int J Cardiol

J Am Coll Cardiol

Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarctionTIMI 11B-ESSENCE meta-analysis

Circulation

A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery diseaseEfficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group

N Engl J Med

Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE

Eur Heart J

Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarctionresults of the thrombolysis in myocardial infarction (TIMI) 11B trial

Circulation

Economic evaluation of enoxaparin sodium versus heparin in unstable anginaa French sub-study of the ESSENCE trial

Pharmacoeconomics

Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patientsresults from the ESSENCE randomized trial (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events)

Circulation

Combination enoxaparin and abciximab therapy during percutaneous coronary intervention“NICE guys finish first”

J Invasive Cardiol

Initial experience with the low-molecular-weight heparin, enoxaparin, in combination with the platelet glycoprotein IIb/IIIa blocker, tirofiban, in patients with non-ST segment elevation acute coronary syndromes

J Invasive Cardiol

Clinical investigation: acute ischemic heart disease
Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study¹