Enoxaparin Versus Tinzaparin in Non-ST-Segment Elevation Acute Coronary Syndromes - EVET
The goal of the EVET trial was to compare the efficacy of the low molecular weight heparins (LMWHs) enoxaparin versus tinzaparin in patients with non-ST-segment elevation acute coronary syndromes (NSTACS).
Patients Enrolled: 438
Mean Follow Up: 30 days
Mean Patient Age: mean age 65 years
Clinical suspicion of NSTACS, defined as anginal pain at rest for at least 10 minutes, occurring <24 hours before randomization, and ECG changes compatible with the clinical diagnosis (new ST-segment depression ≥0.1 mV, T wave inversion >0.1 mV in at least two adjacent leads, transient ST-segment elevation ≥0.1 mV not justifying thrombolysis, or previously known left bundle branch block with known coronary artery disease)
Persistent ST-segment elevation ≥0.1 mV in two adjacent leads, angina with an established precipitating cause, body weight outside the range of 40-110 kg, contraindications to antithrombotic therapy, administration of oral anticoagulants, pregnancy, and severe renal failure
Composite of recurrent angina, MI, or death at day seven
Primary endpoint at day 30 and the individual events at days seven and 30
Patients were randomized to enoxaparin (subcutaneous 100 IU/kg twice daily, equivalent to 1 mg/kg twice daily; n=220), or tinzaparin (175 IU/kg once daily; n=218) for up to seven days.
Aspirin, intravenous nitrate infusion, beta-blockers, and calcium antagonists, unless contraindicated. All patients were initially treated conservatively, and percutaneous coronary intervention or coronary artery bypass surgery was not performed until after day three.
The composite seven-day primary endpoint was lower in the enoxaparin arm compared with the tinzaparin arm (12.3% vs. 21.1%, p=0.015). Among the components of the composite at seven days, recurrent angina was lower with enoxaparin than with tinzaparin (11.8% vs. 19.3%, p<0.05), but there was no difference in death (0.5% vs. 0.9%) or myocardial infarction (MI; 0.5% vs. 1.8%).
At day 30, the composite endpoint remained lower in the enoxaparin arm (17.7% vs. 28.0%, p=0.012), as did recurrent angina (17.3% vs. 26.1%) and MI (0.5% vs. 2.8%, respectively). The rate of revascularization was also lower in the enoxaparin arm at day seven (8.6% vs. 17.9%, p=0.010) and day 30 (16.4% vs. 26.1%, p=0.019). Rates of serious hemorrhage by day seven did not differ in the two treatment arms (3.6% vs. 3.2%).
Among patients with NSTACS, treatment with the LMWH enoxaparin was associated with a reduction in the primary endpoint of recurrent angina, MI, or death by day seven compared with the LMWH tinzaparin. The difference in the primary composite endpoint was driven primarily by differences in recurrent angina.
The present trial showed that LMWHs are not equally effective in the treatment of patients with NSTACS. Despite the apparent benefit of enoxaparin over tinzaparin, it should be noted that the present study was open label and conducted at a single center.
Additionally, the dose of tinzaparin was selected based on experience in treatment of deep vein thrombosis and acute pulmonary embolism and may not have been optimal in NSTACS patients, resulting in possible subtherapeutic antiXa levels toward the end of the dosing interval. Despite the limitations, the EVET trial was the first randomized head-to-head comparison of two LMWHs in NSTACS patients.
Michalis LK, Katsouras CS, Papamichael N, et al. Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: the EVET trial. Am Heart J 2003;146:304-10.
Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Anticoagulation Management and ACS, EP Basic Science, Aortic Surgery, Cardiac Surgery and Arrhythmias, Interventions and ACS, Interventions and Vascular Medicine
Keywords: Myocardial Infarction, Acute Coronary Syndrome, Enoxaparin, Heparin, Low-Molecular-Weight, Pulmonary Embolism, Bundle-Branch Block, Venous Thrombosis, Electrocardiography, Coronary Artery Bypass, Percutaneous Coronary Intervention
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