Acute coronary syndromes not associated with ST-segment elevation, i.e.
unstable angina and non-Q wave
myocardial infarction, represent a heterogeneous group of clinical disorders sharing similar pathogenic mechanisms, clinical presentation and medical management. Current guidelines recommended an early anti-thrombotic and anti-ischemic treatment in these patients, as well as their prompt risk evaluation based on easily available clinical and instrumental data, to identify those subjects at greater risk in whom a more aggressive management is warranted. Despite the association of
aspirin,
heparin and anti-ischemic drugs, the 30-day rate of death or
myocardial infarction remains high (9-15%) in patients with markers of greater risk (i.e. Braunwald class III, ST-segment depression, abnormal
creatine kinase or
troponin values). Moreover, in patients with
acute coronary syndromes undergoing
percutaneous coronary interventions (PCI), complex coronary lesions increase the peri-procedural risk of thrombotic complications. Regardless of the agonist responsible for platelet activation and aggregation, platelet
glycoprotein (
GP) IIb/IIIa receptor activation is the key factor in
thrombosis formation. Several clinical trials in the past few years have documented the beneficial value of
GP IIb/IIIa inhibitors in patients treated with
aspirin and
heparin, with a significant reduction in the cumulative end-point of death and/or
myocardial infarction at 48-96 hours (odds ratio--OR 0.81, 95% confidence interval--CI 0.71-0.92, p < 0.01). Such therapeutical benefit is still present at 30 days (OR 0.88, 95% CI 0.81-0.97, p < 0.001) and 6 months (OR 0.88, 95% CI 0.79-0.97, p < 0.001). In patients treated with
abciximab,
eptifibatide or
tirofiban, undergoing early PCI, a remarkable relative reduction in the risk of death and non-fatal acute
myocardial infarction was shown before PCI (-34%, p < 0.001). The pre-PCI administration of
GP IIb/IIIa inhibitors is associated with a significant reduction in peri-procedural complications (-41% relative reduction of death or acute
myocardial infarction in the 48 hours after PCI, p < 0.001). In this subset of patients the benefit correlates with abnormal pre-PCI values of
troponin, a reliable
surrogate marker of active
thrombosis. The greatest clinical benefit from
GP IIb/IIIa inhibitors is expected in patients presenting high-risk features (early post-
infarction angina; older age with a history of
left ventricular dysfunction or diabetes;
heart failure symptoms, ST-segment depression, abnormal
troponin,
creatine kinase, and
C-reactive protein values at admission) as well as in patients with recurrent ischemic attacks and those undergoing early PCI. Although the combination of
GP IIb/IIIa inhibition and standard doses of
unfractionated heparin is associated with an increased risk of major
bleeding, such risk can be remarkably reduced adopting simple technical suggestions.