Is Abciximab a Superior Way to Eliminate Elevated Thrombotic Risk in Diabetics - ISAR-SWEET

Description:

The goal of the study was to evaluate treatment with the glycoprotein IIb/IIIa inhibitor abciximab compared with placebo in diabetic patients undergoing elective percutaneous coronary intervention (PCI) and pretreated with clopidogrel.

Hypothesis:

Treatment with abciximab will be associated with a 50% reduction in death or myocardial infarction (MI) at 12 months compared with placebo.

Study Design

Study Design:

Patients Enrolled: 701
Mean Follow Up: 12 months
Mean Patient Age: Mean age 67 years
Female: 25

Patient Populations:

Diabetic patients scheduled to undergo elective PCI in a native coronary vessel and pretreated with clopidogrel 600 mg for >2 hours prior to the procedure

Exclusions:

MI within prior 14 days, unstable angina with ST changes or troponin elevation, target lesion in venous bypass graft, chronic occlusion >3 months, angiographically visible thrombus in target lesion, left ventricular ejection fraction <30%, hemodynamic instability, pericarditis, malignancy, stroke in prior three months, active bleeding, trauma or surgery in prior month, oral anticoagulation therapy, or known allergy to study medication

Primary Endpoints:

Composite of all-cause mortality or MI at 12 months

Secondary Endpoints:

Binary angiographic restenosis at angiographic follow-up, defined as stenosis ≥50%

Drug/Procedures Used:

Patients in both study groups were pretreated with 600 mg clopidogrel for at least two hours prior to the PCI, and 500 mg aspirin. Patients were randomized to abciximab (0.25 mg/kg bolus, 0.125 µg/kg/min infusion for 12 hours) (n=351) or placebo (n=350).

Principal Findings:

Baseline characteristics were well balanced in the treatment groups. Diabetes treatment at baseline was insulin dependent in 29% of patients in the abciximab group and 28% in the placebo group, oral hypoglycemic drugs in 51% in both groups, and no drugs in 20% and 21%, respectively. Multivessel disease was present in 85% and 82% of patients, respectively. Median duration of clopidogrel pretreatment was 6.6 hours in the abciximab group and 6.2 hours in the placebo group.

There was no difference in the primary endpoint of death or MI at 12 months (8.3% for abciximab vs. 8.6% for placebo, p=0.91). There was also no significant difference in death or MI at 12 months in the subgroup of patients presenting with insulin-dependent diabetes (12.0% vs. 14.3%, p=0.66). The secondary endpoint of binary restenosis at angiographic follow-up was lower in the abciximab group (28.9% vs. 37.8%, p=0.01). Additionally, target lesion revascularization was lower in the abciximab group (23.2% vs. 30.4%, p=0.03). There was no difference in major bleeding between the treatment groups (1.1% vs. 0.9%, p=NS), but both minor bleeding (3.4% vs. 1.4%, p=0.09) and transfusions (2.3% vs. 0.5%, p=0.11) trended higher in the abciximab group.

Interpretation:

Among diabetic patients undergoing elective PCI and pretreated with high-dose clopidogrel, treatment with abciximab was not associated with a difference in the primary endpoint of death or MI at 12 months compared with placebo, but was associated with a lower rate of binary restenosis and target lesion revascularization.

These data are similar to the ISAR REACT trial, which showed no difference in 30-day major cardiac events with abciximab compared with placebo in low-risk patients undergoing PCI who were pretreated with 600 mg clopidogrel. While there was no difference in the primary endpoint of death or MI in the present trial, it should be noted that the trial was powered to detect a 50% reduction with abciximab, a relatively large improvement in clinical events that may have been overestimated. Only 10% of patients in the trial were treated with a drug-eluting stent.

References:

Mehilli J, Kastrati A, Schuhlen H, et al. Randomized Clinical Trial of Abciximab in Diabetic Patients Undergoing Elective Percutaneous Coronary Interventions After Treatment With a High Loading Dose of Clopidogrel. Circulation 2004;110:[Epub ahead of print].

Presented by Julinda Mehilli at the American Heart Association Scientific Sessions, November 2004, New Orleans, LA.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Ticlopidine, Immunoglobulin Fab Fragments, Insulins, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Hypoglycemic Agents, Diabetes Mellitus


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