Limitation of Myocardial Infarction Following Thrombolysis in Acute - LIMIT AMI
The LIMIT AMI trial was designed to determine the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the B2 integrin adhesion receptors (rhuMAb CD18), in acute MI patients treated with a thrombolytic agent.
Patients receiving rhuMAb CD18 would have faster CTFCs and a higher proportion of TIMI 3 flow at 90 minutes following thrombolytic administration compared with placebo patients.
Patients Enrolled: 394
NYHA Class: not reported
Mean Follow Up: 90 days
Mean Patient Age: not reported
Mean Ejection Fraction: not reported
Chest pain >30 minutes duration with ST-segment elevation; >=1 mm in >=2 contiguous leads on a 12-lead ECG; Eligible for treatment with front-loaded.
Symptom duration >12 hours; oral temperature >=101.5°F; treatment with any thrombolytic agent within 4 days; previous coronary surgery; cardiogenic shock; inability to undergo cardiac catheterization; major surgery, biopsy of a parenchymal organ, or significant trauma within 3 months; prolonged cardiopulmonary resuscitation within 2 weeks; recent noncompressible vascular puncture; LBBB; systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg; bleeding disorder within the past 6 months; any history of stroke, TIA, or central nervous system structural damage; therapeutic oral anticoagulation; pregnancy; parturition within 30 days; childbearing potential not using adequate birth control methods; active infection or current use of oral antibiotics; other serious illness; other illnesses or therapies known to impair the immune system.
Corrected TIMI frame count (CTFC) at 90 minutes
TIMI grade 3 flow at 90-minute angiography Myocardial infarct size assessed by SPECT at >=120 hours ECG ST-segment elevation resolution at 3 hours TIMI myocardial perfusion grade during angiography ECG ST-segment resolution immediately before angiography
Randomization at a 1:1:1 ratio of 0.5 mg/kg or 2.0 mg/kg rhuMAb CD18 or matching placebo administered before commencing rtPA or as soon as possible thereafter.
rtPA plus aspirin (325 mg) and IV heparin (4000 to 5000 U bolus, followed by 800 to 1000 U/h). The target aPTT was 55-80 seconds. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >=120 hours.
There were no treatment effects on coronary blood flow as assessed using CTFC (median frames 33 vs 38 vs 35 for placebo vs low-dose vs high dose) or TIMI grade 3 flow (66% vs 58% vs 63%, respectively). The incidence of TIMI grade 3 flow in the placebo group was unexpectedly high (66%). The rate of TIMI myocardial perfusion grade 2 or 3 did not differ between the three groups (48% vs 55% vs 49% for placebo vs low-dose vs high dose). Neither infarct size or the rate of ECG ST-segment elevation resolution differed between the placebo and rhuMAb CD18 arms. There was no excess of any specific adverse event in the rhuMAb CD18 groups, including serious or life-threatening bleeding; however, there was a slight trend toward an increase in bacterial infections with rhuMAb CD18 (p=0.33). White cell count increased from a baseline of approx. 11,000 cells/mL in all groups to a peak of 16,000 to 17,000 at 24 hours in both rhuMAb CD18 groups. There were no significant differences between groups in the incidence of recurrent MI, heart failure, or a composite end point (death, recurrent MI, and serious/severe heart failure) at day 30.
Despite positive findings in experimental animal studies, rhuMAb CD18 was well tolerated but lacked any beneficial cardiac effects in patients with ST-segment elevation AMI. Medications with possible activity against leukocyte adhesion, such as unfractionated heparin and abciximab, could have influenced the effects of rhuMAb CD18. There may be other receptors other than the CD18 receptor also involved in adhesion and migration that were not inhibited.
Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Cell Count, Heparin, Bacterial Infections, Immunoglobulin Fab Fragments, Fibrinolytic Agents, Electrocardiography, Integrins, Leukocytes, Chest Pain, Heart Failure
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