Enoxaparin vs Unfractionated Heparin in High-Risk Patients With Non–ST-Segment Elevation Acute Coronary Syndromes Managed With an Intended Early Invasive Strategy
Topic: Anticoagulation in acute coronary syndrome (unfractionated heparin and low molecular weight heparin)
Aim:
- Compare enoxaparin to unfractionated heparin in low- to moderate-risk patients with non–ST-segment elevation acute coronary syndromes (ACS) treated with a early invasive strategy
Design:
- Prospective international, multi-centered, open labeled, randomized clinical trial
Treatment:
- Enoxaparin 1mg/kg every 12 hours
Control:
- Unfractionated heparin 60 U/kg, max 5000 U bolus, then 12 mg/kg/hr infusion
Cohort:
- 10,027 participants
Inclusion criteria:
- Ischemic symptoms lasting at least 10 minutes occurring within 24 hours before enrollment
- At least 2 of the following: (i) ≥ 60 years of age, (ii) troponin or creatinine kinase elevation above upper limit of normal, (iii) ST-segment changes on ECG
- Managed with an intended early invasive treatment strategy
Exclusion criteria:
- Known or suspected pregnancy
- Contraindications to unfractionated heparin or enoxaparin
- Recent or planned spinal or epidural anesthesia or puncture
- PCI or thrombolytics within preceding 24 hours
- Increased risk for bleeding complications due to recent stroke or surgery
- Elevated INR of > 1.5
- Past or present bleeding disorder
- Creatinine clearance less than 30 mL/min
- Streptokinase therapy during the last year
- Heparin therapy within 2 h before study medications
- Known renal insufficiency (serum creatinine 2.0 mg/dl or 1.77 mmol/liter)
Follow up:
- 30 days
Primary endpoint:
- Composite all cause death or nonfatal MI during the first 30 days after randomization
Secondary endpoint:
- Composite of death, nonfatal MI, stroke or recurrent ischemia requiring revascularization, and individual components of this composite at 14 and 30 days
Main results:
- The primary intention-to-treat analyses included 4993 patients assigned to receive enoxaparin and 4985 patients assigned to receive unfractionated heparin.
- Median time from randomization to angiography was 22 hours.
- At 30 days, there was no significant difference in the primary composite end point of all-cause death or nonfatal MI in patients treated with enoxaparin or UFH (14% vs. 14.5%; CI 0.86-1.06). Enoxaparin was not superior, but fulfilled the non-inferiority criteria.
- Bleeding was modestly increased in patients assigned to enoxaparin, with a nonsignificant excess in GUSTO severe events (p =0.08), although TIMI major bleeding was significantly higher in patients treated with enoxaparin (p=0.008). The majority of the absolute bleeding excess resulted from CABG-related events and no significant differences in transfusion, intracranial hemorrhage, or thrombocytopenia were observed.
- The reinfarction rate during the five days of study treatment was lower in the lepirudin group (1% vs. 2.5%, p=0.048) but similar at 30 days.
- The combined incidences of death or nonfatal reinfarction at 30 days were similar between groups (10.4% vs 11% in lepirudin- and heparin-treated patients, respectively).
- The incidences of major and minor bleedings were similar in both treatment groups.
TAKE AWAY: Enoxaparin is non-inferior to unfractionated heparin in reducing a primary composite endpoint of all-cause death or non-fatal MI, at expense of a modest increase risk of bleeding, in high risk patients with non-STEMI treated with early invasive strategy.
