GP IIb/IIIa Inhibitors and PCI in Clopidogrel Nonresponders - GP IIb/IIIa Inhibitors and PCI in Clopidogrel Nonresponders

Description:

The goal of the trial was to evaluate routine treatment with the glycoprotein (GP) IIb/IIIa inhibitor abciximab in addition to standard therapy during elective percutaneous coronary intervention (PCI) in nonresponders to clopidogrel.

Hypothesis:

Tailored therapy with the routine use of the GP IIb/IIIa inhibitor abciximab would be more effective in improving clinical outcomes.

Study Design

Study Design:

Patients Screened: 643
Patients Enrolled: 149
Mean Follow Up: 1 month
Mean Patient Age: 66 years
Female: 45%
Mean Ejection Fraction: 62%

Patient Populations:

  • Patients at least 18 years of age with stable angina or a positive stress test undergoing elective PCI with stent implantation to a native coronary artery

Exclusions:

  • Left ventricular ejection fraction <30%
  • Acute coronary syndrome within the prior month
  • Prior myocardial infarction in the target vessel
  • Thrombocytopenia (<100 g/L)
  • History of bleeding diathesis

Primary Endpoints:

  • Composite of all-cause mortality, periprocedural myonecrosis, stent thrombosis, or recurrent ischemia requiring rehospitalization and repeat coronary angiography

Drug/Procedures Used:

Nonresponders to clopidogrel who were undergoing elective PCI were randomized to routine abciximab (n = 74) versus conventional therapy where a GP IIb/IIIa inhibitor could be used at operator discretion (n = 75).

All patients received 250 mg of aspirin and 600 mg of clopidogrel before PCI. Nonresponse to clopidogrel was defined as high platelet reactivity (adenosine diphosphate-induced aggregation >70%).

Principal Findings:

Among 643 patients undergoing elective PCI, 23% were determined to be nonresponders to clopidogrel. The mean age was 66 years, 45% of participants were women, and mean ejection fraction was 62%. There were two patients in the conventional therapy group that received a GP IIb/IIIa inhibitor. The mean stent diameter was 3.0 mm and the mean total stent length was 24 mm.

The composite primary outcome occurred in 19% of the abciximab group vs. 40% of the conventional therapy group (p = 0.006). The number of deaths was 0 vs. 1, number of stent thromboses was 0 vs. 1, number of patients with periprocedural myonecrosis was 13 vs. 26, and number of rehospitalizations for ischemia was 1 vs. 2, respectively, for routine GP IIb/IIIa inhibitor vs. conventional therapy. No patient in either group had a major bleed or required a blood transfusion.

Interpretation:

Among clopidogrel nonresponders undergoing elective PCI, the routine use of abciximab in addition to pre-PCI aspirin and clopidogrel reduced composite outcomes at 1 month of follow-up. The composite outcome was driven by a reduction in periprocedural myonecrosis after PCI, which was defined as a troponin I greater than 0.4 ng/ml. There were no major bleeds in either group.

This trial complements several other trials that tested the same concept. In the 3T/2R trial, the use of tirofiban reduced periprocedural myonecrosis compared with placebo among aspirin or clopidogrel nonresponders. Another trial defined clopidogrel nonresponsiveness according to the vasodilator-stimulated phosphoprotein (VASP) phosphorylation index, and found that additional dosing of clopidogrel reduced adverse cardiac events.

There are multiple tests for aspirin and/or clopidogrel nonresponsiveness, and the preferred mechanism to test for this condition is not known. While conceptually attractive, it is also unknown if the reduction in periprocedural myonecrosis will result in improved clinical outcomes.

References:

Cuisset T, Frere C, Quilici J, et al. Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders. A prospective, randomized study. J Am Coll Cardiol Intv 2008;1:649-53.

Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Heart Failure and Cardiac Biomarkers, Chronic Angina

Keywords: Platelet Aggregation Inhibitors, Angina, Stable, Coronary Disease, Ticlopidine, Immunoglobulin Fab Fragments, Platelet Membrane Glycoprotein IIb, Vasodilator Agents, Tyrosine, Stents, Percutaneous Coronary Intervention, Blood Transfusion, Troponin I, Thrombosis, Coronary Vessels, Exercise Test, Platelet Glycoprotein GPIIb-IIIa Complex


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