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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 and long-term benefit after PCI, and one agent
(abciximab) has also demonstrated a progressive long-term
mortality benefit. The long-term mortality benefit is highly
cost-effective when compared to other medical interventions.
Percutaneous treatment of aortocoronary saphenous vein graft
stenotic disease represents a viable option for patients with
recurrent angina following coronary artery bypass grafting.
Present 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/IIa 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
chimeric antibody 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. The inhibition, however, is
partial, and varied depending on type of ECM protein and alpha(v)beta(3)
integrin expression. Some of the clinical benefits of c7E3
Fab may be due to its effect on SMCs.
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