[The clinical use of the GPIIb/IIIa inhibitors eptifibatide and tirofiban in the treatment of acute coronary syndromes of the "non-ST elevation" type].
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.
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Divisione di Cardiologia, Fondazione Salvatore Maugeri, IRCCS, Veruno. mgalli@fsm.it
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Vassanelli
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D000208:Acute Disease; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000175:diagnosis / Q000188:drug therapy*; D004562:Electrocardiography; D000077542:Eptifibatide; D006801:Humans; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D013577:Syndrome; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide