Coronary artery disease
Effectiveness and Safety of Glycoprotein IIb/IIIa Inhibitors and Clopidogrel Alone and in Combination in Non–ST-Segment Elevation Myocardial Infarction (from the National Registry of Myocardial Infarction-4)

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We investigated whether a combination of clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors safely decreases hospital mortality, reinfarction, and major bleeding beyond either therapy alone in patients with non–ST-elevation myocardial infarction (NSTEMI). GP IIb/IIIa inhibitors and clopidogrel, separately, have been shown to decrease adverse outcomes in patients with non–ST-elevation acute coronary syndromes, but the need for combination therapy is uncertain. Multivariate and propensity analyses compared the frequency of death, reinfarction, and major bleeding during hospitalization in 38,691 patients with NSTEMI who were enrolled in the National Registry of Myocardial Infarction 4 from July 2000 to December 2003. Of these, 65% received GP IIb/IIIa inhibitors only, 16.1% clopidogrel only, and 18.8% combination therapy. Among patients who did not undergo percutaneous coronary intervention (PCI), the composite end point of death, reinfarction, and major bleeding was significantly lower with combination therapy than with GP IIb/IIIa inhibitors alone (odds ratio 0.77, 95% confidence interval 0.67 to 0.88). In contrast, this composite end point was significantly higher when combination therapy was employed rather than clopidogrel alone (odds ratio 1.55, 95% confidence interval 1.33 to 1.81). However, among patients who underwent PCI, the composite end point was similar between combination therapy and GP IIb/IIIa inhibitor-only groups (odds ratio 1.01, 95% confidence interval 0.89 to 1.14). Further, there was a strong trend toward a higher composite end point among patients who received combination therapy rather than clopidogrel alone (odds ratio 1.31, 95% confidence interval 0.99 to 1.72). In conclusion, commonly employed strategies using a GP IIb/IIIa inhibitor alone or with the combination of clopidogrel plus GP IIb/IIIa inhibitor in NSTEMI may not be justified in comparison with a simpler strategy of clopidogrel used alone, especially in patients who have not undergone PCI.

Section snippets

Data collection

The National Registry of Myocardial Infarction (NRMI) is a voluntary registry of cross-sectional data on patients hospitalized with confirmed myocardial infarction. Trained abstractors collected detailed data from the records of 632,146 patients admitted between July 2000 and December 2003 at 1,290 participating hospitals. The characteristics of the registry, data-gathering procedures, and reliability have been reported elsewhere.1, 2, 3 For patients included in the NRMI, the diagnosis of

Study population

Table 1 presents patients’ clinical and demographic characteristics. There was a larger proportion of women and older patients in the clopidogrel-only group. That group also had a larger proportion of patients with preexisting chronic renal insufficiency, myocardial infarction, hypertension, cerebrovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, peripheral vascular disease, and previous coronary bypass graft surgery. There was a larger

Discussion

The main finding in this observational analysis is that, in patients with NSTEMI who did not undergo PCI, clopidogrel-only therapy is associated with a significant decrease in the composite of in-hospital mortality, reinfarction, and major bleeding compared with combination and GP IIb/IIIa inhibitor-only therapies. A second important finding in this study is that, in patients with NSTEMI who underwent PCI, a possible mortality benefit with combination therapy over patient therapy with a GP

References (23)

  • Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes

    N Engl J Med

    (1998)
  • Cited by (14)

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    • Underutilization of clopidogrel and glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute coronary syndrome patients: The Canadian Global Registry of Acute Coronary Events (GRACE) experience

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    The National Registry of Myocardial Infarction is funded by Genentech, Inc., South San Francisco, California. This analysis was supported by an unrestricted grant from Genentech, Inc.

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