The Benefits of Platelet Glycoprotein IIb/IIIa Receptor Inhibition During Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction. Drug-Specific or Class Effect?

Journal of the American College of Cardiology (Impact Factor: 16.5). 06/2009; 53(18):1674-6. DOI: 10.1016/j.jacc.2009.02.009
Source: PubMed


For patients with ST-segment elevation (acute) myocardial infarction (STEMI), reperfusion with primary percutaneous coronary intervention (PCI) results in excellent short-and long-term outcome, predominantly because of the high rate of restoration of normal flow at the epicardial and myocardial levels (1). Despite its success, primary PCI remains fraught with obstacles because of the high thrombus burden, difficulty in initial assessment of lesion length and vessel size, and consequences of distal embolization of plaque and thrombus. Thus, adjunctive pharmacology has always been an important tool for addressing these challenges. Oral and intravenous platelet inhibitors and intravenous thrombin inhibitors have been used in various combinations to reduce thrombus size and prevent its reaccumulation after successful reperfusion.

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Available from: Sorin J Brener
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    • "A very recent meta-analysis [12] of 6 randomized trials on STEMI patients involving 2197 patients showed that abciximab did not reduce 30-day mortality (2.2% vs. 2.0%, p = 0.66) or re-infarction (1.2% vs. 1.2%, p = 0.88), nor was there any difference in major bleeding complications (1.3% vs. 1.9%, p = 0.27). Thus, among STEMI patients undergoing primary PCI, similar results between abciximab and small molecules in terms of angiographic, electrocardiographic, and clinical outcome [12] may dictate the selection of the less expensive among these agents [13], especially if a class-effect is present, as quite recently hypothesized [14, 15]. "
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    ABSTRACT: There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world. We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression. There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17). In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did.
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    ABSTRACT: Antiplatelet therapy is critical in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Current antiplatelet agents (aspirin, clopidogrel and glycoprotein IIb/IIIa antagonists) have demonstrated the capacity to reduce major adverse cardiac events. However, these agents have limitations that compromise their clinical utility. The platelet P2Y12 receptor plays a central role in platelet function and is a focus in the development of antiplatelet therapies. Cangrelor is a potent, competitive inhibitor of the P2Y12 receptor that is administered by intravenous infusion and rapidly achieves near complete inhibition of ADP-induced platelet aggregation. This investigational drug has been studied for use during coronary procedures and the management of patients experiencing acute coronary syndrome and is undergoing evaluation for use in the prevention of perioperative stent thrombosis.
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