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- Three platelet glycoprotein (GP) IIb/IIIa receptor
antagonists have been approved as adjunctive therapy to decrease the
ischemic complications of percutaneous coronary interventions (PCI)
and/or unstable angina. They include the chimeric murine/human monoclonal
antibody 7E3 Fab fragment (abciximab; ReoPro®; Lilly), a cyclic
heptapeptide based on the KGD amino acid sequence (eptifibatide; INTEGRILIN®;
Cor/Schering), and a nonpeptide mimetic of the RGD sequence (tirofiban;
AGGRASTAT®; Merck).
- The agents are very effective in providing both
short-term benefit after PCI. Present PCI strategies are limited by
high rates of distal embolization, non-Q-wave acute myocardial infarction
(AMI), and restenosis. Because these complications may be mediated by
platelets, inhibition of platelet glycoprotein IIb/IIIa receptor, the
final common pathway for aggregation, may improve clinical outcomes.
- Several patient subgroups appear to benefit
preferentially from inhibition of platelet glycoprotein (GP) IIb/IIIa
receptors. In clinical trials the GP IIb/IIIa blocker abciximab proved
both safe and effective in improving outcomes after coronary interventions.
- In a study reported by Mak KH and associates
(Am J Cardiol. 1997 Oct 15;80(8):985-8), a total of 101 patients
were treated for saphenous vein graft stenoses. Clinical end points
included all-cause mortality, nonfatal AMI and need for repeat revascularization
at 30 days. Compared with placebo, bolus and infusion therapy resulted
in a significant reduction in distal embolization (2% vs 18%, p
= 0.017) and a trend towards reduction in early large non-Q-wave
AMI (2% vs 12%, p = 0.165). . These results suggest that adjunctive
therapy with abciximab during percutaneous treatment of saphenous
vein grafts stenoses reduces the occurrence of distal embolization,
and possibly non-Q-wave AMI. Other GP IIb/IIIa eptifibatide , and
tirofiban have also benefited patients with the acute coronary syndromes
(e.g., unstable angina) by decreasing ischemic events.
- Brief intravenous administration of abciximab
during coronary angioplasty has been shown in some studies to provide
long term protection against coronary events. Smooth muscle cell (SMC)
adhesion and migration are key initial steps in the development of restenosis.
- Baron JH, and associates demonstrated (Cardiovasc
Res. 2000 Dec;48(3):464-72) that abciximab inhibits the adhesion
and migration of SMCs via the alpha(v)beta(3) integrin.
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