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      The Role of Glycoprotein IIb/IIIa Inhibitors- A Promise Not Kept?

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      Current Cardiology Reviews
      Bentham Science Publishers Ltd.

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          Abstract

          For over one decade Glycoproteins IIb/IIIa inhibitors (GPI) have been administered to prevent coronary artery thrombosis. Initially these agents were used for acute coronary syndromes and subsequently as adjunctive pharmacotherapy for percutaneous coronary interventions (PCIs).

          Most benefit of GPI emerged from reduction of ischemic events: mostly non-q-wave myocardial infarctions (NQWMIs) during PCI. However, individual randomized clinical trials could not demonstrate that any of these agents could significantly reduce mortality in any clinical subset of patients. Studies of employing prolonged oral GPI administration resulted in excessive death. The non-homogenous statistically-significant reduction of ischemic endpoints was accompanied by an excess of bleeding, vascular complications, and thrombocytopenia. The clinical and ecomomic burden of major bleeding and thrombocytopenia is substantial. The ACUITY trial has initiate a new debate regarding the efficacy and safety of GPI.

          Selective “patient-tailored” use of GPI limited to moderate-high risk PCI patients with low bleeding propensity is suggested. Research of new algorithms emphasizing abbreviated GPI administration, careful access site and bleeding surveillance, in conjunction with lower doses of unfractionated heparin or new and safer anti-thrombins may further enhance patient safety.

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          Most cited references88

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          Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.

          There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.
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            Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.

            Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI. 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat. There were no drop-outs. 59 (4.5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6.4%) in the placebo group (relative risk 0.70 [95% CI 0.50-0.97], p=0.03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0.03), and of cardiovascular death or myocardial infarction (p=0.047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0.002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0.001). At follow-up, there was no significant difference in major bleeding between the groups (p=0.64). In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.
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              Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology.

              In patients with stable CAD, PCI can be considered a valuable initial mode of revascularization in all patients with objective large ischaemia in the presence of almost every lesion subset, with only one exception: chronic total occlusions that cannot be crossed. In early studies, there was a small survival advantage with CABG surgery compared with PCI without stenting. The addition of stents and newer adjunctive medications improved the outcome for PCI. The decision to recommend PCI or CABG surgery will be guided by technical improvements in cardiology or surgery, local expertise, and patients' preference. However, until proved otherwise, PCI should be used only with reservation in diabetics with multi-vessel disease and in patients with unprotected left main stenosis. The use of drug-eluting stents might change this situation. Patients presenting with NSTE-ACS (UA or NSTEMI) have to be stratified first for their risk of acute thrombotic complications. A clear benefit from early angiography (<48 h) and, when needed, PCI or CABG surgery has been reported only in the high-risk groups. Deferral of intervention does not improve outcome. Routine stenting is recommended on the basis of the predictability of the result and its immediate safety. In patients with STEMI, primary PCI should be the treatment of choice in patients presenting in a hospital with PCI facility and an experienced team. Patients with contra-indications to thrombolysis should be immediately transferred for primary PCI, because this might be their only chance for quickly opening the coronary artery. In cardiogenic shock, emergency PCI for complete revascularization may be life-saving and should be considered at an early stage. Compared with thrombolysis, randomized trials that transferred the patients for primary PCI to a 'heart attack centre' observed a better clinical outcome, despite transport times leading to a significantly longer delay between randomization and start of the treatment. The superiority of primary PCI over thrombolysis seems to be especially clinically relevant for the time interval between 3 and 12 h after onset of chest pain or other symptoms on the basis of its superior preservation of myocardium. Furthermore, with increasing time to presentation, major-adverse-cardiac-event rates increase after thrombolysis, but appear to remain relatively stable after primary PCI. Within the first 3 h after onset of chest pain or other symptoms, both reperfusion strategies seem equally effective in reducing infarct size and mortality. Therefore, thrombolysis is still a viable alternative to primary PCI, if it can be delivered within 3 h after onset of chest pain or other symptoms. Primary PCI compared with thrombolysis significantly reduced stroke. Overall, we prefer primary PCI over thrombolysis in the first 3 h of chest pain to prevent stroke, and in patients presenting 3-12 h after the onset of chest pain, to salvage myocardium and also to prevent stroke. At the moment, there is no evidence to recommend facilitated PCI. Rescue PCI is recommended, if thrombolysis failed within 45-60 min after starting the administration. After successful thrombolysis, the use of routine coronary angiography within 24 h and PCI, if applicable, is recommended even in asymptomatic patients without demonstrable ischaemia to improve patients' outcome. If a PCI centre is not available within 24 h, patients who have received successful thrombolysis with evidence of spontaneous or inducible ischaemia before discharge should be referred to coronary angiography and revascularized accordingly--independent of 'maximal' medical therapy.
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                Author and article information

                Journal
                Curr Cardiol Rev
                CCR
                Current Cardiology Reviews
                Bentham Science Publishers Ltd.
                1573-403X
                1875-6557
                May 2008
                : 4
                : 2
                : 84-91
                Affiliations
                []Department of Cardiology, University Medical Center, University of Medicine and Dentistry, Newark, NJ, USA
                Author notes
                [* ]Address correspondence to this author at the Invasive Cardiology and Cardiac Catheterization Laboratories, University Hospital, University of Medicine and Dentistry of New Jersey, 185 South Orange Ave, MSB I-538, Newark, 07101, USA; Tel: 973-972-4731; Fax: 973-972-1592; E-mail: kalusked@ 123456umdnj.edu (w), ekaluski@ 123456gmail.com (travel)
                Article
                CCR-4-84
                10.2174/157340308784245793
                2779356
                19936282
                18579ddf-fa13-4595-a82a-b88d8754a8ae
                ©2008 Bentham Science Publishers Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 March 2007
                : 17 May 2007
                : 30 May 2007
                Categories
                Article

                Cardiovascular Medicine
                Cardiovascular Medicine

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