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Review |

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

Gilles Montalescot, MD, PhD; Maria Borentain, MD; Laurent Payot, MD; Jean Philippe Collet, MD, PhD; Daniel Thomas, MD
[+] Author Affiliations

Author Affiliations: Institut de Cardiologie, Pitié-Salpêtrière University Hospital, Paris, France.


JAMA. 2004;292(3):362-366. doi:10.1001/jama.292.3.362.
Text Size: A A A
Published online

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.

Figures in this Article

Primary percutaneous coronary intervention (PCI) is widely regarded as the reperfusion strategy of choice in ST-segment elevation myocardial infarction (STEMI),1 but only a minority of STEMI patients present directly to PCI centers, while the vast majority present initially to their emergency ambulance service and/or to local hospitals and require transfer to a tertiary center for primary PCI. Despite the attendant delay, we confirmed in a recently published meta-analysis the superiority of transfer for primary PCI over local thrombolysis.2 The absence or negligible use of glycoprotein IIb/IIIa (Gp IIb/IIIa) antagonists in the primary PCI arms of the studies of this meta-analysis may have reduced the magnitude of benefit observed with primary PCI. Indeed, 5 randomized studies have now shown a significant 30-day reduction in death or nonfatal MI or urgent revascularization with Gp IIb/IIIa antagonists,37 with a pooled analysis confirming further a significant 34% reduction of death or MI and a nonsignificant 26% reduction of mortality.8

The initial experience of exporting Gp IIb/IIIa inhibitors out of the catheterization laboratory was described in the Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-term Follow-up (ADMIRAL) randomized study in which, for a subset of patients, treatment occurred in the emergency department or even in the ambulance prior to arrival in the catheterization laboratory.3 The magnitude of the drug effect was increased dramatically in this subgroup compared with the rest of the population treated later in the catheterization laboratory.

More recently, several small angiographic studies have been performed to test the timing issue of Gp IIb/IIIa inhibitors in a randomized fashion.914 Half of these studies have been inconclusive on angiographic end points,11,13,14 and all have been too small to make meaningful conclusions regarding clinical end points. We therefore decided to perform a systematic meta-analysis.

Study Objectives and Design

Our primary aim was to compare, in STEMI, immediate treatment with Gp IIb/IIIa inhibitors prior to arrival in the catheterization laboratory vs a later administration of Gp IIb/IIIa inhibitors just before primary PCI. STEMI was defined according to the inclusion criteria of the trials concerned. It was recognized that there would be heterogeneity in the studies and that transfer times as well as patient management were likely to be variable. On the other hand, by combining the studies, even if case-specific data were not available, the statistical power to detect a difference in time effect might be substantially increased.

Trial Search Strategy

We conducted a MEDLINE and Cochrane Controlled Trials Register search of the literature to identify all randomized trials published in the last 10 years that compared early vs delayed administration of Gp IIb/IIIa inhibitors in STEMI. In addition, we searched for papers presented at major cardiac conferences. National and international colleagues as well as Gp IIb/IIIa inhibitor drug manufacturers were consulted. Finally, text and journal article bibliographies were hand searched. From these trials, specific "early vs late" studies were identified, defined as those in which randomization occurred outside the catheterization laboratory.

Study Selection and Data Extraction

We restricted our meta-analysis to trials that performed a randomized comparison 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 on admission by TIMI flow grades and mortality. Two authors (G.M., M.B.)independently reviewed abstracts or complete articles. Only 6 nonoverlapping studies met the inclusion criteria. Independent data extraction was performed by 2 reviewers and confirmed by consensus.

End Points and Definitions

The primary angiographic end point was the combined TIMI grade 2 and 3 flows on the first angiogram, which defined open culprit artery on admission. TIMI grade 3 flow was also assessed separately. The primary clinical end point was all-cause mortality at longest follow-up. The composite ischemic end point at longest follow-up, as defined in each study, was also assessed separately.

Statistical Analysis

The results from each trial were those obtained on an intention-to-treat basis. The meta-analysis was performed using the odds ratio (OR) as the parameter of efficacy with a fixed effect model (Mantel-Haenszel),15 with appropriate tests for association and heterogeneity. Finally, the number of patients needed to be treated to avoid 1 event (NNT) was calculated for each end point using the overall weighted risk difference (NNT = 1/[absolute risk difference]).

The P value for significance of association and heterogeneity tests was set at .05. The statistical analysis was performed using EasyMA software.15

Trial Patient Characteristics and Study Designs

Six trials were identified with a design including randomization to immediate vs delayed administration of Gp IIb/IIIa inhibitors for primary PCI, in which randomization took place outside the catheterization laboratory.914 The trial names, acronyms, patient characteristics, and details of the study groups are shown in Table 1.

Table Graphic Jump LocationTable. Summary of Characteristics in Trials Comparing Immediate vs Delayed Administration of Glycoprotein IIb/IIIa Inhibitors for Primary Angioplasty

Enrollment criteria of chest pain (<6 or <12 hours) with ST elevation or new left bundle-branch block on the electrocardiogram were used throughout (Table 1). Trial design was broadly similar in all studies; however, there were some differences regarding site of randomization: in 4 studies, randomization occurred in the emergency department of the PCI center1012,14; in 1 study, randomization was performed at the scene of presentation outside the hospital and the drug was given during ambulance transportation13; and in the last study, patients could be enrolled and randomized in the ambulance, at referring hospitals, or in the emergency department of the PCI center but always before transfer to the catheterization laboratory.9 One of the 6 randomized studies was double-blind, placebo-controlled.9 The same dose regimen of tirofiban was used throughout the 3 tirofiban studies with a bolus of 10 µg/kg followed by a 0.15 µg/kg/min infusion,911 and the same dose regimen of abciximab was used throughout the 3 abciximab studies with an intravenous bolus of 0.25 mg/kg followed by a 0.125 µg/kg/min infusion (to a maximum of 10 µg/min).1214

Mortality data were available at 1 month follow-up in 3 studies,10,11,14 at 6-month follow-up in 2 studies,12,13 and at 1-year follow-up in the last study.9 The use of a 30-day composite ischemic end point of death, reinfarction, or urgent revascularization was also consistent throughout the studies with a few differences between trials, as indicated in Table 1.

Angiographic End Points

The proportion of patients with TIMI grade 2 or 3 flow was significantly higher with an early administration of Gp IIb/IIIa inhibitors in only 3 of the 6 trials.9,10,12 Combining all 6 trials together, early administration of Gp IIb/IIIa inhibitors was associated with a marked and highly significant increase in open infarct arteries as indicated by a TIMI grade 2 or 3 flow rate of 41.7% vs 29.8% with a late administration (OR, 1.69; 95% confidence interval [CI], 1.28-2.22; P<.001 [Figure 1]). There was no evidence of heterogeneity, and the overall NNT was 8 for this primary angiographic end point. Odd ratios were similar for the 2 tested drugs with a nonsignificant interaction test for the type of drug.

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.

The proportion of patients with TIMI grade 3 flow on the initial angiogram was greatly increased in the early administration group (Figure 2). The overall NNT was 12 for achievement of TIMI grade 3 flow.

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.
Clinical Outcomes

The mortality rates varied between trials, and none of the 6 trials showed a significant difference between the 2 study groups. Combining the trials, there was a 28% reduction in mortality in the early administration group (16/467 [3.4%]) compared with the late administration group (22/466 [4.7%]), which did not reach statistical significance (Figure 3). There was no evidence of heterogeneity, and the ORs were similar for the 2 tested drugs with a nonsignificant interaction test for the type of drug. A similar favorable trend was found in the group receiving GP IIb/IIIa inhibitors early for the composite ischemic end point (OR, 0.78; 95% CI, 0.51-1.20; P = .32) and for MI as individual component of this end point (OR = 0.73, 95% CI, 0.31-1.77; P = .64).

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.

Because small trials are more prone to be affected by publication bias, we constructed funnel plots for both angiographic and clinical end points that exhibited a fairly symmetrical distribution and convergence toward the pooled effect when the weight of the trials increased, suggesting that publication or selection bias was unlikely.

The attendant delay for primary PCI may limit its clinical benefit over thrombolysis, especially when patients present within 3 hours after the onset of symptoms.16,17 It has been argued that "early pharmacologic facilitation" during the transfer period to the catheterization laboratory may improve outcome, although the efficacy of this strategy remains to date unproven. There is robust evidence for the superiority of Gp IIb/IIIa inhibition over placebo in primary PCI.38,1821 However, the huge majority of patients recruited in Gp IIb/IIIa inhibition clinical trials received treatment relatively late, at the time of PCI.

In the ADMIRAL study, the analysis of the prespecified subgroup that received abciximab in the emergency department or in the ambulance showed better outcomes than the group of patients receiving the drug later, suggesting an advantage of "facilitation."3 However, to definitively demonstrate facilitating efficacy requires randomization against placebo, immediate administration of the study drug on presentation, and similar pharmacologic treatment in both study arms during and after PCI. The 6 studies we identified fulfilled these requirements.

The major finding of our meta-analysis is the demonstration of a probable "facilitating" effect of Gp IIb/IIIa inhibitors for improving angiographic patency of the culprit artery. TIMI flow on initial angiography is likely of clinical importance since it has been shown to be a major determinant of survival in primary PCI22 and a valid surrogate end point for mortality in thrombolytic trials.23 The early administration of Gp IIb/IIIa inhibitors was also associated with consistent and favorable trends for mortality, reinfarction, and the composite ischemic end point, although these differences remained nonsignificant.

Short time to treatment is a well-known factor for clinical benefit with thrombolysis24 and with primary PCI.2528 It appears that the same time-to-treatment paradigm applies to Gp IIb/IIIa inhibitors when they are used in conjunction with primary PCI. This time factor in the drug effect may also explain some of the discrepancies observed between primary PCI trials that had different designs for the time of drug administration.3,5,8

The current meta-analysis has a number of limitations, including inevitable clinical heterogeneity between trials and an overall sample size of only 931 patients, which is adequate for TIMI grade 2 or 3 flow (power of 97%) but insufficient for clinical outcomes. Sensitivity analyses were also performed and comparable results were obtained with a random effect model or when the largest study was excluded from the meta-analysis. Our analyses were also limited to short-term outcomes, but Gp IIb/IIIa inhibitor studies have often demonstrated increasing survival benefit with longer follow-up.29,30 In spite of the various limitations, however, the individual trials were in most cases underpowered and the combined analysis allows more robust conclusions.

Our data support strongly several hypotheses developed in recent years regarding what constitutes optimal myocardial reperfusion: first, the "open artery hypothesis"; second, the "dethrombotic" effect of Gp IIb/IIIa inhibitors31,32; third, the key role of time to treatment to improve outcomes; fourth, the concept of "facilitated" PCI, which still needs to be confirmed for clinical outcome; and fifth, the need to develop and/or consolidate prehospital/emergency department systems in the chain of care provided for STEMI patients. Whether more aggressive pharmacologic approaches using a full regimen of thrombolytics or reduced dose of lytics combined with Gp IIb/IIIa inhibitors can open more arteries more rapidly with finally improved clinical outcomes is so far unknown. Recent studies have suggested little impact on infarct size and clinical outcomes of these new facilitating strategies,33 which now need to be tested in large-scale trials such as the Safety and Efficacy of a New Thrombolytic (ASSENT)-4 and Facilitated Intervention with Enhanced reperfusion Speed to Stop Events' (FINESSE) trials.

In conclusion, in STEMI patients treated with Gp IIb/IIIa inhibitors, there appears to be significant angiographic benefit with favorable trends for clinical outcome when treatment is started at first medical contact before transfer to the catheterization laboratory. Further evaluations in adequately powered large trials are awaited to confirm the clinical benefit of this strategy.

Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials.  Lancet.2003;361:13-20.
PubMed
Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis.  Circulation.2003;108:1809-1814.
PubMed
Montalescot G, Barragan P, Wittenberg O.  et al.  Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.  N Engl J Med.2001;344:1895-1903.
PubMed
Brener SJ, Barr LA, Burchenal JE.  et al. for the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.  Randomized, placebo controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction.  Circulation.1998;98:734-741.
PubMed
Stone GW, Grines CL, Cox DA.  et al.  Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.  N Engl J Med.2002;346:957-966.
PubMed
Neumann FJ, Kastrati A, Schmitt C.  et al.  Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction.  J Am Coll Cardiol.2000;35:915-921.
PubMed
Antoniucci D, Rodriguez A, Hempel A.  et al.  A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction.  J Am Coll Cardiol.2003;42:1879-1885.
PubMed
Topol EJ, Neumann FJ, Montalescot G. A preferred reperfusion strategy for acute myocardial infarction.  J Am Coll Cardiol.2003;42:1886-1889.
PubMed
Van't Hof AWJ, Ernst N, DeBoer MJ.  et al.  Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) trial.  Eur Heart J.2004;25:837-846.
PubMed
Lee DP, Herity NA, Hiatt BL.  et al.  Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the Tirofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial.  Circulation.2003;107:1497-1501.
PubMed
Cutlip DE, Ricciardi MJ, Frederick SL.  et al.  Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction.  Am J Cardiol.2003;92:977-980.
PubMed
Zorman S, Zorman D, Noc M. Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty.  Am J Cardiol.2002;90:533-536.
PubMed
Arntz H-R, Schroder JF, Pels K.  et al.  Prehospital versus periprocedural administration of abciximab in STEMI: early and late results from the randomised REOMOBILE-study.  Eur Heart J.2003;24(abstract suppl):268.
Mesquita Gabriel H, Oliveira J, Canas da Silva P.  et al.  Early administration of abciximab bolus in the emergency room improves microperfusion after primary percutaneous coronary intervention, as assessed by TIMI frame count: results of the ERAMI trial.  Eur Heart J.2003;24(abstract suppl):543.
Cucherat M, Boissel JP, Leizorovicz A, Haugh MC. EasyMA: a program for the meta-analysis of clinical trials.  Comput Methods Programs Biomed.1997;53:187-190.
PubMed
Widimsky P, Groch L, Zelizko M.  et al.  Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory: the PRAGUE study.  Eur Heart J.2000;21:823-831.
PubMed
Steg PG, Bonnefoy E, Chabaud S.  et al.  Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial.  Circulation.2003;108:2851-2856.
PubMed
Van den Merkhof LF, Zijlstra F, Olsson H.  et al.  Abciximab in the treatment of acute myocardial infarction eligible for primary percutaneous transluminal coronary angioplasty: results of the Glycoprotein Receptor Antagonist Patency Evaluation (GRAPE) pilot study.  J Am Coll Cardiol.1999;33:1528-1532.
PubMed
Glatt B, Luycx-Bore A, Guyon P.  et al.  Pre-hospitalization treatment with abciximab in the preparation of patients for primary angioplasty in the acute phase of myocardial infarct: immediate and long-term (one month) results.  Arch Mal Coeur Vaiss.1999;92:1301-1308.
PubMed
Makkar R, Goff B, Eigler N.  et al.  Effect of glycoprotein IIb/IIIa inhibition without thrombolytic therapy on reperfusion of acute myocardial infarction: results of ReoMI pilot study.  Catheter Cardiovasc Interv.1999;48:430-434.
PubMed
Antman EM, Giugliano R, Gibson CM.  et al.  Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI)14 trial.  Circulation.1999;99:2720-2732.
PubMed
Stone GW, Cox D, Garcia E.  et al.  Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials.  Circulation.2001;104:636-641.
PubMed
The GUSTO investigators.  The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function and survival after acute myocardial infarction.  N Engl J Med.1993;329:1615-1622.
PubMed
Fibrinolytic Therapy Trialists' (FTT) Collaborative Group.  Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients.  Lancet.1994;343:311-322.
PubMed
De Luca G, Suryapranata H, Zijlstra F.  et al.  Symptom-onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty.  J Am Coll Cardiol.2003;42:991-997.
PubMed
Cannon CP, Gibson CM, Lambrew CT.  et al.  Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction.  JAMA.2000;283:2941-2947.
PubMed
Antoniucci D, Valenti R, Migliorini A.  et al.  Relation of time to treatment and mortality in patients with acute myocardial infarction undergoing primary coronary angioplasty.  Am J Cardiol.2002;89:1248-1252.
PubMed
Brodie BR, Stuckey TD, Wall TC.  et al.  Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction.  J Am Coll Cardiol.1998;32:1312-1319.
PubMed
Anderson KM, Califf RM, Stone GW.  et al.  Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention.  J Am Coll Cardiol.2001;37:2059-2065.
PubMed
Lincoff AM, Califf RM, Topol EJ. Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease.  J Am Coll Cardiol.2000;35:1103-1115.
PubMed
Collet JP, Montalescot G, Lesty C.  et al.  Disaggregation of in vitro pre-formed platelet-rich clots by abciximab increases fibrin exposure and promotes fibrinolysis.  Arterioscler Thromb Vasc Biol.2001;21:142-148.
PubMed
Collet JPh, Montalescot G, Lesty CL.  et al.  Effects of abciximab on the architecture of platelet-rich clot in patients with acute myocardial infarction undergoing primary coronary intervention.  Circulation.2001;103:2328-2331.
PubMed
Kastrati A, Mehilli J, Schlotterbeck K.  et al.  Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial.  JAMA.2004;291:947-954.
PubMed

Figures

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.

Tables

Table Graphic Jump LocationTable. Summary of Characteristics in Trials Comparing Immediate vs Delayed Administration of Glycoprotein IIb/IIIa Inhibitors for Primary Angioplasty

References

Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials.  Lancet.2003;361:13-20.
PubMed
Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis.  Circulation.2003;108:1809-1814.
PubMed
Montalescot G, Barragan P, Wittenberg O.  et al.  Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.  N Engl J Med.2001;344:1895-1903.
PubMed
Brener SJ, Barr LA, Burchenal JE.  et al. for the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.  Randomized, placebo controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction.  Circulation.1998;98:734-741.
PubMed
Stone GW, Grines CL, Cox DA.  et al.  Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.  N Engl J Med.2002;346:957-966.
PubMed
Neumann FJ, Kastrati A, Schmitt C.  et al.  Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction.  J Am Coll Cardiol.2000;35:915-921.
PubMed
Antoniucci D, Rodriguez A, Hempel A.  et al.  A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction.  J Am Coll Cardiol.2003;42:1879-1885.
PubMed
Topol EJ, Neumann FJ, Montalescot G. A preferred reperfusion strategy for acute myocardial infarction.  J Am Coll Cardiol.2003;42:1886-1889.
PubMed
Van't Hof AWJ, Ernst N, DeBoer MJ.  et al.  Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) trial.  Eur Heart J.2004;25:837-846.
PubMed
Lee DP, Herity NA, Hiatt BL.  et al.  Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the Tirofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial.  Circulation.2003;107:1497-1501.
PubMed
Cutlip DE, Ricciardi MJ, Frederick SL.  et al.  Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction.  Am J Cardiol.2003;92:977-980.
PubMed
Zorman S, Zorman D, Noc M. Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty.  Am J Cardiol.2002;90:533-536.
PubMed
Arntz H-R, Schroder JF, Pels K.  et al.  Prehospital versus periprocedural administration of abciximab in STEMI: early and late results from the randomised REOMOBILE-study.  Eur Heart J.2003;24(abstract suppl):268.
Mesquita Gabriel H, Oliveira J, Canas da Silva P.  et al.  Early administration of abciximab bolus in the emergency room improves microperfusion after primary percutaneous coronary intervention, as assessed by TIMI frame count: results of the ERAMI trial.  Eur Heart J.2003;24(abstract suppl):543.
Cucherat M, Boissel JP, Leizorovicz A, Haugh MC. EasyMA: a program for the meta-analysis of clinical trials.  Comput Methods Programs Biomed.1997;53:187-190.
PubMed
Widimsky P, Groch L, Zelizko M.  et al.  Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory: the PRAGUE study.  Eur Heart J.2000;21:823-831.
PubMed
Steg PG, Bonnefoy E, Chabaud S.  et al.  Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial.  Circulation.2003;108:2851-2856.
PubMed
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