Meta-Analysis of Randomized Trials of Glycoprotein IIb/IIIa Inhibitors in High-Risk Acute Coronary Syndromes Patients Undergoing Invasive Strategy

Study Questions:

What is the comparative effectiveness of a strategy of upstream administration of glycoprotein (GP) IIb/IIIa inhibitors, aimed at cooling the culprit coronary plaque before angioplasty, to a strategy of downstream selective administration of such drugs?


The investigators obtained results from all randomized trials on this issue. The literature was scanned by formal searches of electronic databases from January 1990 to March 2010. The following key words were used: “randomized trial,” “myocardial infarction,” “ACS,” “coronary angioplasty,” “upstream,” “downstream,” “GP IIb/IIIa inhibitors,” “abciximab,” “tirofiban,” and “eptifibatide.” Primary and secondary clinical endpoints were mortality and myocardial infarction at 30 days, respectively. Major bleeding complications were assessed as a safety endpoint.


Seven randomized trials were included in the meta-analysis, involving 19,929 patients (9,981 or 50.0% in the upstream GP IIb/IIIa inhibitors group and 9,948 or 50% in the downstream GP IIb/IIIa inhibitors group). Upstream GP IIb/IIIa inhibitors did not decrease 30-day mortality (2.0% vs. 2.0%, p = 0.84) or recurrence of myocardial infarction (7.0% vs. 7.6%, p = 0.11), but were associated with higher risk of major bleeding complications (1.8% vs. 1.3%, p = 0.0002).


The authors concluded that in high-risk patients with acute coronary syndrome (ACS) undergoing an early invasive strategy, upstream administration of GP IIb/IIIa inhibitors does not improve clinical outcome compared to a downstream selective administration.


The primary finding of this meta-analysis is that in high-risk ACS patients undergoing an early invasive strategy, routine upstream administration of GP IIb/IIIa inhibitors compared to selective downstream administration does not provide benefits for death and myocardial infarction, and is associated with a significantly higher risk of major bleeding complications. Increased use of more powerful P2Y12 inhibitors will probably further decrease potential benefits from unselected upstream administration of GP IIb/IIIa inhibitors. Based on available evidence, unselected upstream administration of GP IIb/IIIa inhibitors should be discouraged.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, ACS and Cardiac Biomarkers, Heart Failure and Cardiac Biomarkers, Interventions and ACS

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Peptides, Pharmaceutical Preparations, Immunoglobulin Fab Fragments, Angioplasty, Balloon, Coronary, Tyrosine, Platelet Membrane Glycoprotein IIb, Platelet Glycoprotein GPIIb-IIIa Complex

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