Intravenous glycoprotein IIb/IIIa inhibition in non-ST segment elevation acute coronary syndromes
Section snippets
Summary of platelet biology
Before considering the clinical trials, a discussion of the platelet physiology and the glycoprotein IIb/IIIa antagonist pharmacology may provide a biologic basis for interpreting the varied results. Beyond adhesion and aggregation, platelets secrete prothrombotic and proinflammatory cytokines, express adhesion/signaling molecules involved in the inflammatory process, and provide the essential phospholipid membrane that facilitates thrombin generation.[8], [9], [10] As the principle molecule
The glycoprotein IIb/IIIa inhibitor pharmacology
Currently, 3 intravenous glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban) have been approved for clinical use. Owing to the lack of overall efficacy within 2 phase III ACS trials, the development of a fourth agent, lamifiban, has ceased. Similarly, the development of orally active platelet glycoprotein IIb/IIIa inhibitors for chronic platelet inhibition has stalled because of a consistent increase in mortality observed within 5 large-scale randomized clinical trials.18
Clinical trials
Collectively, the clinical experience of the glycoprotein IIb/IIIa inhibitors for the management of non-ST segment elevation myocardial infarction (MI) ACS spans 7 randomized placebo-controlled trials, including over 30,000 patients.[1], [2], [3], [4], [6], [38] These data show an overall benefit associated with the use of glycoprotein IIb/IIIa inhibition in addition to aspirin and unfractionated heparin among high-risk patients presenting with coronary instability.[39], [40] Nevertheless, a
Gender
In comparison with men, an excess rate of adverse outcome often has been observed among women presenting with ACS. Most of this excess risk is attributable to older age and the greater prevalence of cardiac risk factors among women. Nevertheless, gender-related differences in platelet physiology and thrombotic potential have been noted, although the clinical relevance of these differences remains speculative.[46], [47] Approximately 30% of the patients enrolled within the ACS trials have been
Conclusion
Given the diverse spectrum of risk associated with the diagnosis of non-ST segment elevation ACS and the wide array of treatment strategies, the moderate overall benefit observed within the clinical trials of the glycoprotein IIb/IIIa inhibitors is not altogether unexpected. Although some trials show results that remain statistically significant, inclusion of low-risk patients and low rates of PCI in several studies contribute to an overall impression of marginal benefit associated with the use
Acknowledgments
The authors thank Ms. Donna Bressan for her expert editorial assistance in the preparation of this manuscript.
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