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Early vs Late Administration of Glycoprotein IIb/IIIa Inhibitors in Primary Percutaneous Coronary Intervention of Acute ST-Segment Elevation Myocardial Infarction A Meta-analysis

Gilles Montalescot, MD, PhD; Maria Borentain, MD; Laurent Payot, MD; Jean Philippe Collet, MD, PhD; Daniel Thomas, MD
JAMA. 2004;292(3):362-366. doi:10.1001/jama.292.3.362.
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Context Glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors improve myocardial reperfusion and clinical outcomes of patients undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. No systematic reviews have comprehensively examined the effects of early vs delayed administration of these agents.

Objective To perform a meta-analysis of randomized trials of early (prior to transfer to the catheterization laboratory) vs late (at the time of PCI) intravenous administration of Gp IIb/IIIa inhibitors in acute ST-segment elevation myocardial infarction (STEMI).

Data Sources MEDLINE and the Cochrane Controlled Trials Register search of the literature over the past 10 years; papers presented at major cardiac conferences; consultation with national and international colleagues as well as Gp IIb/IIIa inhibitor drug manufacturers; and text and journal article bibliographies.

Study Selection and Data Extraction We examined trials of randomized comparisons between early administration at the point of initial contact (emergency department or ambulance) and late administration (catheterization laboratory) of Gp IIb/IIIa inhibitors in STEMI. Outcome data had to be available on both culprit artery patency evaluated by Thrombolysis in Myocardial Infarction (TIMI) flow grades on admission and mortality. Two authors independently reviewed abstracts or complete articles. Six studies met inclusion criteria. Independent data extraction was performed by 2 reviewers and confirmed by consensus.

Data Synthesis The 6 trials enrolled 931 STEMI patients treated with abciximab (3 trials) or tirofiban (3 trials) in combination with primary PCI. TIMI grade 2 or 3 flow (41.7% [194/465 vs 29.8% [139/466]) as well as TIMI grade 3 flow (20.3% [84/413] vs 12.2% [51/418]) were significantly more frequent in the early group compared with the late group (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.28-2.22; P<.001; and OR, 1.85; 95% CI, 1.26-2.71; P<.001, respectively). The early administration of Gp IIb/IIIa inhibitors was associated with a 28% reduction of mortality from 4.7% to 3.4%, which was not significant but consistent with similar trends for reinfarction and the composite ischemic end point.

Conclusions In a meta-analysis of 6 randomized trials, early administration of Gp IIb/IIIa inhibitors in STEMI appeared to improve coronary patency with favorable trends for clinical outcomes. These findings are supportive of a strategy of facilitated PCI. Further evaluations in adequately powered large trials are awaited to confirm the clinical benefit of this strategy.

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Figure 1. Odds Ratios for Thrombolysis in Myocardial Infarction (TIMI) Grade 2 or 3 Flow With Early vs Late Administration of Glycoprotein IIb/IIIa Inhibitors
Graphic Jump Location
Overall odds ratio, 1.69 (95% confidence interval [CI], 1.28-2.22; P<.001). Breslow-Day test for heterogeneity, P = .23. On-TIME indicates Ongoing Tirofiban in Myocardial Infarction Evaluation trial; TIGER-PA, Tirofiban Given in the Emergency Room before Primary Angioplasty trial; ERAMI, Early ReoPro Administration in Myocardial Infarction trial.
Figure 2. Odds Ratios for Thrombolysis in Myocardial Infarction (TIMI) Grade 3 Flow With Early vs Late Administration of Glycoprotein IIb/IIIa Inhibitors
Graphic Jump Location
Overall odds ratio, 1.85 (95% confidence interval [CI], 1.26-2.71; P<.001). Breslow-Day test for heterogeneity, P = .12. Data available in 5 of the 6 trials. See Figure 1 for expansions of acronyms.
Figure 3. Odds Ratios for Mortality With Early vs Late Administration of Glycoprotein IIb/IIIa Inhibitors
Graphic Jump Location
Overall odds ratio, 0.72 (95% confidence interval [CI], 0.37-1.40; P = .42. Breslow-Day test for heterogeneity, P = .34. See Figure 1 for expansions of acronyms.

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