Elsevier

American Heart Journal

Volume 144, Issue 3, September 2002, Pages 470-477
American Heart Journal

Clinical Investigations: Acute Ischemic Heart Disease
Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: The ACUTE II study,☆☆,

https://doi.org/10.1067/mhj.2002.126115Get rights and content

Abstract

Background In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding. Objective Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with enoxaparin plus ASA. Methods Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days. Results The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively). Conclusions Combination therapy with tirofiban plus enoxaparin appears safe, relative to therapy with tirofiban plus UFH. (Am Heart J 2002;144:470-7.)

Section snippets

Subjects

A total of 525 patients who were at higher risk for ischemic events and had UA/NSTEMI were enrolled. The entry criteria included prolonged (≥20 minutes) or repetitive episodes of angina at rest or with minimal effort within the previous 24 hours and either evidence by means of electrocardiogram (ECG) of myocardial ischemia or abnormal cardiac markers. Electrocardiographic changes included new ST-segment depression, transient elevation ≥1 mm, or T-wave inversions (in ≥3 leads). Abnormal cardiac

Study population

Five hundred twenty-five patients were enrolled at 54 participating study sites (see Appendix); 210 patients were randomized to receive UFH, and 315 patients were randomized to receive enoxaparin. The baseline patient demographic and clinical characteristics are shown in Table I.

. Baseline patient demographic/clinical characteristics of the study population

Empty CellTirofiban + UFH (n = 210)Tirofiban + enoxaparin (n = 315)
Age (y)
 Mean ± SD63.7 ± 12.964.6 ± 11.7
 Range33-9434-92
Sex (%)
 Male141 (67.1)207 (65.7)
 

Discussion

In this prospective, randomized study involving 525 patients, we found that coadministration of tirofiban and enoxaparin was well tolerated, with very few significant bleeding events, as classified by means of the TIMI criteria, relative to tirofiban and UFH. These observations are consistent with the results of a 55-patient pilot study,11 which showed that plasma clearance of tirofiban and the bleeding time were comparable whether coadministered with enoxaparin or UFH. This pilot study,

Acknowledgements

We thank Annemarie Thornton and Denise Manas, medical program coordinators from Merck, for the time and effort provided for this initiative and all the investigators and the worldwide Merck medical monitors and staff from clinical research operations.

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Supported by Merck Research Laboratories, West Point, Pa.

☆☆

Reprint requests: Marc Cohen, MD, Cardiac Cath Lab MS-119, Hahnemann University Hospital, Broad and Vine Streets, Philadelphia, PA 19102-1192.

E-mail: [email protected]

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