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J Am Coll Cardiol, 2007; 49:1517-1524, doi:10.1016/j.jacc.2006.12.036 (Published online 26 March 2007).
© 2007 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: CLINICAL TRIAL

Randomized Early Versus Late Abciximab in Acute Myocardial Infarction Treated With Primary Coronary Intervention (RELAx-AMI Trial)

Mauro Maioli, MD*, Francesco Bellandi, MD, Mario Leoncini, MD, Anna Toso, MD and Roberto Piero Dabizzi, MD

Division of Cardiology, Misericordia e Dolce Hospital, Prato, Italy.

Manuscript received July 27, 2006; revised manuscript received December 6, 2006, accepted December 10, 2006.

* Reprint requests and correspondence: Dr. Mauro Maioli, Via degli Arcipressi 3, 50143, Florence, Italy. (Email: mauromaioli{at}tiscali.it).


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Objectives: This prospective randomized trial evaluates the impact of early abciximab administration on angiographic and left ventricular function parameters.

Background: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear.

Methods: Two-hundred ten consecutive patients with first AMI undergoing primary PCI were randomized to abciximab administration either in the emergency room (early group: 105 patients) or in the catheterization laboratory, after coronary angiography (late group: 105 patients). Primary end points were initial Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and myocardial blush grade (MBG), as well as left ventricular function recovery as assessed by serial echocardiographic evaluations.

Results: Angiographic pre-PCI analysis showed a significantly better initial TIMI flow grade 3 (24% vs. 10%; p = 0.01), cTFC (78 ± 30 frames vs. 92 ± 21 frames; p = 0.001), and MBG 2 or 3 (15% vs. 6%; p = 0.02) favoring the early group. Consistently, post-PCI tissue perfusion parameters were significantly improved in the early group, as assessed by 60-min ST-segment reduction ≥70% (50% vs. 35%; p = 0.03) and MBG 2 or 3 (79% vs. 58%; p = 0.001). Left ventricular function recovery at 1 month was significantly greater in the early group (mean gain ejection fraction 8 ± 7% vs. 6 ± 7%, p = 0.02; mean gain wall motion score index 0.4 ± 0.3 vs. 0.3 ± 0.3, p = 0.03).

Conclusions: In patients with AMI treated with primary PCI, early abciximab administration improves pre-PCI angiographic findings, post-PCI tissue perfusion, and 1-month left ventricular function recovery, possibly by starting early recanalization of the infarct-related artery.

Abbreviations and Acronyms
  AMI = acute myocardial infarction
  cTFC = corrected Thrombolysis In Myocardial Infarction frame count
  EF = ejection fraction
  IRA = infarct-related artery
  LV = left ventricle/ventricular
  MACE = major adverse cardiac events
  MBG = myocardial blush grade
  PCI = percutaneous coronary intervention
  STEMI = ST-segment elevation myocardial infarction
  TIMI = Thrombolysis In Myocardial Infarction
  WMSI = wall motion score index

Investigations on glycoprotein IIb/IIIa inhibition in acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) have shown the efficacy of abciximab in improving clinical and angiographic outcome (1–5), reflected in a class IIa recommendation in both the current European Society of Cardiology and American College of Cardiology/American Heart Association guidelines on the management of STEMI. Adjunctive abciximab therapy is associated with a significant reduction in 30-day reinfarction and in short- and long-term mortality in patients with STEMI treated with primary angioplasty (6). Moreover, early administration of abciximab in STEMI, before arrival in the catheterization laboratory, appeared to improve coronary patency with superior pre-PCI Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 compared with late administration (7). However, the impact of abciximab on myocardial perfusion has not yet been well established. In this prospective randomized trial on patients with acute myocardial infarction (AMI) treated with primary stenting, we evaluated the impact on angiographic outcome, microvascular reperfusion, myocardial salvage, and left ventricular (LV) function of abciximab administered in the emergency room compared with abciximab administered in the catheterization laboratory.


   Methods
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 Abstract
 Methods
Results
 Discussion
 References
 
Population and trial protocol.   Consecutive patients with first AMI candidates for primary PCI, irrespective of age, presenting within 12 h of symptom onset with ST-segment elevation of more than 1 mm in at least 2 contiguous leads of the electrocardiogram were considered for randomization. Computerized open-label randomization assignments in blinded envelopes were used in a consecutive fashion in the emergency room.

From June 2003 to March 2006, 232 consecutive patients with AMI were directly referred to our hospital, which provides a round-the-clock service of primary PCI, with 4 trained physicians and dedicated nurses. Two-hundred ten patients with first AMI were enrolled: 105 patients were randomly assigned to the early group and 105 to the late group. Twenty-two patients were excluded. Exclusion criteria were previous myocardial infarction; previous PCI or coronary artery bypass surgery; left bundle branch block; bleeding diathesis; administration of thrombolytic agents for the current episode; recent stroke; uncontrolled hypertension; recent surgery; oral anticoagulant therapy; and known contraindications to therapy with abciximab, aspirin, clopidogrel, or heparin. To better analyze regional and global LV function after the index event, we excluded patients with previous AMI who likely had pre-existent asynergies. Stent implantation was successfully completed in all patients; the choice of stent (bare-metal stent or drug-eluting stent) was left to the operator’s discretion. We attempted direct stenting only in cases presenting clear pictures of the arterial lesion. Otherwise, the patient is subjected to angioplasty, and stenting is done subsequently. The protocol was approved by the institutional ethics committee, and all eligible patients gave informed consent. The first 55 patients enrolled underwent a scintigraphic evaluation before and after PCI; the results of the scintigraphic study were recently published (8). The present study represents the final report of the trial.

Randomized patients received abciximab (0.25 mg/kg as a bolus followed by a 12-h infusion of 0.125 µg/kg/min) either in the emergency room (early group) or in the catheterization laboratory after diagnostic angiography just before PCI (late group). After randomization, all patients received heparin as a bolus of 70 U/kg (maximum 7,000 U) together with 250 mg of aspirin intravenously, in the emergency room. If necessary, additional boluses of heparin were administered to achieve an activated clotting time of 200 s. After PCI, a 24-h infusion of 7 U/kg/h of heparin was performed. The target activated partial-thromboplastin time was between 1.5 and 2.0 times the control value. Immediately after the procedure, all patients received clopidogrel (300 mg). Patients were routinely treated with aspirin (100 mg/day indefinitely) and clopidogrel (75 mg/day for at least 1 month). After discharge, patients entered a clinical follow-up.

Invasive procedure and angiographic evaluation.   Coronary angiography was performed by the femoral approach. All patients underwent primary PCI and stenting of the infarct-related artery (IRA) according to standard technique. Initial and postprocedural TIMI flow grade, corrected TIMI frame count (cTFC), and myocardial blush grade (MBG) of the IRA were assessed off-line by a blinded experienced interventionalist (A.T.), as previously described (9–11). Quantitative coronary angiography (QCA) was performed with a use of an automatic edge detection system (Siemens Acom Quantcor QCA, Munich, Germany). Procedural success was defined as residual stenosis <20% and TIMI flow grade 3 (12).

Electrocardiographic, echocardiographic, and metabolic data.   The 12-lead electrocardiogram was recorded at presentation, immediately before PCI, and continuously 180 min after coronary artery recanalization. Sum of ST-segment elevations was measured in 3 contiguous leads with the highest ST-segment elevation. ST-segment elevation was measured to the nearest 0.5 mm at 60 ms after the J point with the aid of hand-held calipers. ST-segment resolution (before and within 60 min after PCI) was defined as the ratio between pre-intervention or post-intervention values and initial sum of ST-segment elevation. According to a previous report (13), complete ST-segment resolution was defined as a ≥70% decrease in ST-segment elevation 60 min after recanalization of the IRA.

Left ventricular ejection fraction (EF) was assessed by echocardiography (Sonos 5500, Agilent Technologies Inc., Palo Alto, California) according to Simpson in classical 2- and 4-chamber apical projections, at arrival in the emergency room and at 1-month follow-up. Wall motion was scored 1 through 5 according to a 16-segment model, and wall motion score index (WMSI) was calculated as the sum of segmental score divided by the number of visualized segments (14). Electrocardiographic and echocardiographic analysis was performed by the investigator who was blinded to the randomization.

Creatine kinase (CK), its myocardial fraction (CK-MB), plasma cardiac troponin I, and myoglobin measurements were systematically assessed at admission, immediately before diagnostic angiography, at 30 min, 60 min, 90 min, and every 3 h for the subsequent 24 h after PCI, then every day up to discharge, unless clinical events suggested repeat measurements. The peak value and 48-h cumulative release for these serum cardiac markers were measured for the estimation of infarct size in each patient (15).

End points of the trial and definitions.   The primary end point of the trial was the pre-interventional angiographic finding evaluated in terms of TIMI flow grade. In addition, we analyzed cTFC and MBG. Secondary end points were infarct size (measured by cumulative release of serum cardiac markers) and LV functional recovery at 1 month (evaluated in terms of echocardiographic EF and WMSI).

Major and minor bleeding were defined according to the TIMI criteria (9). Platelet counts were also monitored for thrombocytopenia, defined as a platelet count of <100,000/mm3. Major adverse cardiac events (MACE) included death, recurrent myocardial infarction, repeat PCI, coronary artery bypass surgery, and stroke. Recurrent myocardial infarction was defined as a new increase in CK-MB fraction of more than 3 times of the upper limit of normal, whether accompanied by chest pain and/or electrocardiographic changes. Urgent revascularization was defined as a repeated coronary revascularization or coronary artery bypass grafting performed within 24 h after the index revascularization procedure. Procedural time was defined as time from angiography to implantation of stent.

Statistical analysis.   Sample Size Calculation
The primary hypothesis of the trial was that early pretreatment at emergency room with abciximab will increase the incidence of TIMI flow grade 3 at initial angiography before PCI, compared with periprocedural abciximab administration. It was expected that early treatment with abciximab would result in an increase in TIMI flow grade 3 from 10% to 20%. With 80% power, and an {alpha} value of 0.05, 95 patients were necessary in each group to show a significant difference in incidence of the primary end point. With regard to drop-outs, at least 105 patients were planned to be included in both groups.

Final Analysis
Categorical variables were presented as counts and proportions (percentages) and compared by Pearson chi-square analysis or Fisher exact test when the calculated sample size of at least 1 cell of a table was <5. Normal distribution of continuous data was tested using a Kolmogorov-Smirnov test. Continuous and normally distributed data are presented as mean ± 1 SD and were compared by unpaired t test; non-normally distributed data are expressed as median with interquartile range, and the Mann-Whitney U test was used to compare differences between 2 groups. Multivariate logistic regression analysis was performed using all potentially relevant variables to identify baseline independent predictors of initial TIMI flow grade 3. The comparison between basal and 1 month echocardiographic data was performed only in surviving patients. All p values are 2-tailed, and statistical significance was defined as a value of p < 0.05. All analyses were performed with SPSS version 13.0 (SPSS Inc., Chicago, Illinois) statistical software.


   Results
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 Abstract
 Methods
 Results
Discussion
 References
 
Our population is represented by 210 patients who underwent primary PCI treated with abciximab; 105 patients were randomly assigned to the early group and 105 to the late group. Figure 1 shows the trial flow and Table 1 the baseline characteristics of the 2 groups. The majority of patients were "not low risk," according to the TIMI criteria (9). Killip class 3 or 4 was found at presentation in 5 patients (5%) of the early group and in 6 patients (6%) of the late group. No significant difference between groups was found in the onset of symptoms to hospital admission time and in the door to balloon time. As expected, the median time between hospital admission and abciximab bolus administration was significantly shorter in the early group (23 min, interquartile range 15 to 37 min) than in the late group (60 min, interquartile range 40 to 88 min). The early treatment group received the abciximab bolus on a median of 55 min (interquartile range 46 to 72 min) before angioplasty (Table 1). Adjunctive therapy received by each treatment group did not differ.


Figure 1
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  		Figure 1 Flow of Patients Through the Trial

AMI = acute myocardial infarction; CABG = coronary artery bypass grafting; LBBB = left bundle branch block; PCI = percutaneous coronary intervention.

 

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  		Table 1 Baseline Clinical Characteristics of the Patients
 
Angiographic and procedural results.   Angiographic and procedural results are summarized in Table 2. Angiographic pre-PCI analysis showed a significant difference in initial TIMI flow grade 3 (early group 24% vs. late group 10%; p = 0.01), cTFC, and MBG 2 or 3, favoring the early group (Table 2, Fig. 2). Direct stenting was feasible in 29% of patients of the early group versus 13% of the late group (p = 0.004), and the procedural time was significantly shorter in the early group (early group 11 ± 7 min vs. late group 15 ± 8 min; p = 0.03). Multivariate analysis identified only early abciximab administration (odds ratio 2.90; 95% confidence interval 1.3 to 6.6; p = 0.01) as an independent predictor of initial TIMI flow grade 3. No differences were found in the post-PCI IRA patency (92% of TIMI flow grade 3 in both groups), and no significant difference was observed in the final cTFC (Table 2). On the contrary, final MBG 2 or 3 was achieved in a significant higher proportion of the early group (79% vs. 58% of the late treatment group; p = 0.001).


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  		Table 2 Angiographic and Procedural Results
 

Figure 2
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  		Figure 2 TIMI Flow and MBG at Basal Angiography

Basal angiography: Thrombolysis In Myocardial Infarction (TIMI) flow (left) and myocardial blush grade (MBG) (right) in the early versus late groups. Both parameters are significantly better in the early abciximab group with a higher percentage of TIMI flow grade 3 and MBG 3 (left: p = 0.001 vs. late group; right: p = 0.028 vs. late group).

 
Electrocardiographic and laboratory results.   Significantly better ST-segment resolution was observed pre-PCI after early administration of abciximab (Table 3). After PCI, significant more frequent complete ST-segment elevation resolution at 60 min was also observed in the early group (50% vs. late group 35%; p = 0.03) (Table 3).


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  		Table 3 Electrocardiographic and Laboratory Results
 
The baseline levels of CK-MB (9 ± 19 ng/ml vs. 10 ± 18 ng/ml) and troponin I (1 ± 3 ng/ml vs. 1 ± 2 ng/ml) were similar in early and late groups, respectively. Analysis of the peak value and 48-h cumulative release for serum cardiac markers revealed a more favorable trend in the early group with a lower release (Table 3).

One-month LV function recovery and clinical outcome.   After 1 month, we obtained 201 paired LV function studies. Even though regional and global LV function parameters were similar at baseline, the increase of 1 month WMSI (early group 0.4 ± 0.3 vs. late group 0.3 ± 0.3, p = 0.03) and the gain of EF (early group 8 ± 7% vs. 6 ± 7%, p = 0.02) were significantly greater in the early group. This group of patients also presented a significantly better WMSI (1.4 ± 0.3 vs. 1.5 ± 0.4, p = 0.01) and EF (51 ± 9% vs. 47 ± 10%, p = 0.01) compared with the late group (Table 4, Fig. 3).


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  		Table 4 One-Month Left Ventricle Function Recovery
 

Figure 3
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  		Figure 3 Left Ventricular Function According to Early and Late Abciximab

Left ventricular function according to early (blue bars) and late (red bars) abciximab. Ejection fraction (EF) (left) and wall motion score index (WMSI) (right) at baseline and at 1 month after primary angioplasty, and mean gain in EF and WMSI between the 2 time points. In the early abciximab patients, both functional parameters were significantly better compared with late abciximab patients (left: p = 0.014 vs. late group; right: p = 0.014 vs. late group); in the same patients, the mean gain in EF (left: p = 0.023 vs. late group) and in WMSI (right: p = 0.031 vs. late group) was significantly higher. Error bars indicate SDs of the mean.

 
One-month clinical follow-up was available in all patients. Cumulative MACE occurred in 15 patients: 6 (5.7%) in the early group and 9 (8.6%; p = 0.42) in the late group. Nine patients (4.3%) died within 1 month, 3 (2.9%) patients in the early group (1 from cardiogenic shock, 1 from sudden death, and 1 from fatal repeat AMI) and 6 patients (5.7%; p = 0.49) in the late group (4 from cardiogenic shock, 1 from free wall rupture, and 1 from fatal repeat AMI). Six patients (2.8%), 2 in the early and 4 in the late group (p = 0.68), had recurrent myocardial infarction. Three patients (1.4%), 2 in the early and 1 in the late group (p = 0.62), had repeated an urgent PCI, and 2 patients (0.9%), 1 in each group, underwent urgent coronary artery bypass grafting.

No differences were noted between the 2 groups with regard to bleeding complications, which occurred in 9 patients (8.6%) of the early group and in 6 patients (5.7%) of the late group (p = 0.44). Minor and major bleeding distribution was not statistically different, with 8 minor bleeds (7.6%) in the early group and 5 (4.8%) in the late group (p = 0.57) and 1 major bleed in each group (1%). No intracranial bleeding event was observed. There were no differences in the blood transfusions: 6 (5.7%) patients in the early group versus 4 (3.8%) patients of the late group (p = 0.75). Thrombocytopenia after abciximab administration was seen in only 5 patients (2.4%), 1 (1%) in the early group and 4 (3.8%) in the late group (p = 0.37).


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
The results of the present trial suggest that, in patients with first AMI treated with PCI, early abciximab administration in the emergency room compared with late in the catheterization laboratory significantly improves preprocedural angiographic epicardial flow (evaluated by TIMI flow grade) and tissue perfusion (MBG 2 or 3). Moreover, post-interventional parameters of myocardial reperfusion (i.e., MBG ≥2 and ST-segment resolution) were also improved, and this is associated with a smaller infarct size and with an improved LV function at 1-month follow-up.

Previous studies showed that primary PCI can be facilitated by intravenous abciximab to improve blood flow both at the epicardial (3) and at the microcirculatory level (16). The majority of large randomized trials demonstrated the benefit of abciximab in AMI (1–4,16,17). De Luca et al. (6) recently showed that, compared with the control group, adjunctive abciximab is associated with a significant reduction of 30-day and long-term (6 to 12 months) mortality (4.4% vs. 6.2%, p = 0.01) in patients undergoing primary PCI, without an increased risk of intracranial bleeding. In a recent pooled analysis of 6 studies (602 cases), comparing early versus late abciximab administration in AMI, the early group received abciximab a median of 50 min before angiography and had a higher proportion of pre-PCI TIMI flow grade 3 (20% vs. 12%), quite similar to our findings (7). Moreover, the early group showed a significantly improved ST-segment resolution within 3 h after PCI and a moderate but nonsignificant reduction in the risk of death, new myocardial infarction, or urgent target vessel revascularization at 30 days. These data are consistent with the results of the present trial, showing a better reduction in ST-segment elevation after PCI in the early group, mirrored by a favorable trend in the clinical outcome at 1 month.

Observational data from the PAMI (Primary Angioplasty in Myocardial Infarction) studies have indicated that, among patients who undergo successful primary PCI, LV function and survival appear to be improved when TIMI flow grade 3 is present before intervention (18). Reasons likely include improved myocardial salvage as well as technically easier aspects of the intervention. In the early group of this trial, the procedural time was shorter and the proportion of direct stenting was higher compared with the late group, despite that mean lesion length was not significantly different between groups. A better IRA flow allows better visualization of lesion length, side branches, thrombus burden, and distal arterial tree; this may facilitate all steps of the procedure, including direct stenting, which has been associated with less slow flow and better ST-segment reduction (19).

Functional recovery is the main mechanism by which patients with AMI benefit from various reperfusion therapies, and it can be assessed by serial echocardiographic evaluations. In this trial, a better functional recovery at 1 month was observed in the early group compared with the late group. This finding is probably correlated to a better initial angiographic outcome at epicardial and myocardial level, since the other baseline angiographic characteristics were similar between the 2 groups. Moreover, the postprocedural angiographic and electrocardiographic parameters of myocardial reperfusion were also improved in the early group despite a similar procedural success at the epicardial level, as assessed by the QCA and the TIMI flow grade analyses. The results agreed with a previous study that showed a strict correlation between the microvascular reperfusion and the recovery of contraction in the infarct zone (12).

Although the single treatment with glycoprotein IIb/IIIa inhibitors alone is not ideally suited to achieve early successful reperfusion, such observations recall the intrinsic anticoagulant and fibrinolytic potential of abciximab (20–22). In an experimental study, Goto et al. (20) have shown that antiglycoprotein IIb/IIIa agents possess the ability to dissolve platelet thrombi formed on the collagene surface under blood flow conditions. This effect might enhance infarct-artery patency before mechanical revascularization (23–25).

Thus, consistent with previous studies correlating early infarct-artery patency with both improved survival and LV function, early abciximab administration before PCI may further enhance treatment benefits. In the setting of facilitated PCI with full or reduced dose thrombolytic drugs, the results of ASSENT-4 PCI (Assessment of the Safety and Efficacy Of a New Treatment Strategy for Acute Myocardial Infarction) trial (26) and a recent meta-analysis (27) show that, despite the improvement of initial TIMI flow grade 3, this approach is associated with increased rates of death, nonfatal reinfarction, urgent target vessel revascularization, bleeding, and stroke. However, a worse clinical outcome and an increased rate of stroke were not reported in patients receiving facilitated regimes with platelet glycoprotein IIb/IIIa inhibitors alone (27).

Such findings support the design of the ongoing trial examining early pharmacologic reperfusion therapy followed by PCI (28). The positive effect of abciximab on microvascular flow can be explained by the prevention of microvascular obstruction potentially caused by embolization of platelet aggregates and microthrombi (29,30). Furthermore, abciximab markedly improves myocardial blood flow regulation in acute coronary syndromes (31), and preserves a coronary blood flow response to acetylcholine after coronary stenting (32). The interaction of abciximab with other receptors, such as the {alpha}vß3 vitronectin (33,34) or the Mac-1 receptor (35,36), may also play a role by preventing leukocyte-mediated injury of microvessels, eventually related to reperfusion.

Study limitations.   This is a prospective, randomized, single-center trial. The sample size of the population was not powered to detect differences in mortality or hard clinical end points. Another limitation of our trial was that operator physicians were not blinded to the treatment assignment. Consequently, bias of the investigators cannot be fully excluded as a factor influencing clinical treatment. Moreover, the event reporting was per investigators without involvement of any independent adjudication committee. However, the physicians evaluating angiographic, electrocardiographic, and echocardiographic parameters were blinded to the assigned treatment. In this way, a possible bias in the assessment of the end points was limited. Furthermore, the study was designed before the use of clopidogrel loading dose as standard therapy in patients undergoing PCI.

Conclusions.   In patients with AMI treated with primary PCI, early abciximab administration improves pre-PCI angiographic findings and 1-month LV function, possibly by starting early recanalization of the IRA.


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Brener SJ, Barr LA, Burchenal JE, et al. 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.[Abstract/Free Full Text]
  2. 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.[Abstract/Free Full Text]
  3. Montalescot G, Barragan P, Wittemberg O, et al. ADMIRAL Investigators Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction N Engl J Med 2001;344:1895-1903.[Abstract/Free Full Text]
  4. 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.[Abstract/Free Full Text]
  5. Montalescot G, Borentain M, Payot L, Collet JP, Thomas D. Early vs. late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis JAMA 2004;292:362-366.[Abstract/Free Full Text]
  6. De Luca G, Suryapranata H, Stone GW, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarctionA meta-analysis of randomized trials. JAMA 2005;293:1759-1765.[Abstract/Free Full Text]
  7. Godicke J, Flather M, Marko N, et al. Early versus periprocedural administration of abciximab for primary angioplasty: a pooled analysis Am Heart J 2005;150:1015.[Medline]
  8. Bellandi F, Maioli M, Leoncini M, Toso A, Dabizzi RP. Early abciximab administration in acute myocardial infarction treated with primary coronary intervention Int J Cardiol 2006;108:36-42.[CrossRef][ISI][Medline]
  9. TIMI Study Group. Definitions used in TIMI trials. Available at: http://www.timi.org. Accessed May 3, 2006.
  10. Gibson CM, Cannon CP, Daley WL, et al. TIMI frame count: a quantitative method of assessing coronary artery flow Circulation 1996;93:879-888.[Abstract/Free Full Text]
  11. van’t Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F, Zwolle Myocardial Infarction Study Group Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade Circulation 1998;97:2302-2306.[Abstract/Free Full Text]
  12. Poli A, Fetiveau R, Vandoni P, et al. Integrated analysis of myocardial blush and ST-segment elevation recovery after successful primary angioplasty: real-time grading of microvascular reperfusion and prediction of early and late recovery of left ventricular function Circulation 2002;106:313-318.[Abstract/Free Full Text]
  13. de Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy J Am Coll Cardiol 2001;38:1283-1294.[Abstract/Free Full Text]
  14. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantification of the left ventricle by two-dimensional echocardiography: American Society of Echocardiography Committee on Standards, Subcommittee on Quantification of Two-Dimensional Echocardiograms J Am Soc Echocardiogr 1989;2:358-367.[Medline]
  15. Gibbons RJ, Valeti US, Araoz PA, Jaffe AS. Quantification of infarct size J Am Coll Cardiol 2004;44:1533-1542.[Abstract/Free Full Text]
  16. Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction Circulation 1998;98:2695-2701.[Abstract/Free Full Text]
  17. Stone GW, Grines CL, Cox AD, et al. CADILLAC Investigators Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction N Engl J Med 2002;346:957-966.[Abstract/Free Full Text]
  18. 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.[Abstract/Free Full Text]
  19. Loubeyre C, Morice MC, Lefevre T, Piechaud P, Louvard Y, Dumas P. A randomized comparison of direct stenting with conventional stent implantation in selected patients with acute myocardial infarction J Am Coll Cardiol 2002;39:15-21.[Abstract/Free Full Text]
  20. Goto S, Tamura N, Ishida H. Ability of anti-glycoprotein IIb/IIIa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions J Am Coll Cardiol 2004;44:316-323.[Abstract/Free Full Text]
  21. Reverter JC, Beguin S, Kessels H, Kumar R, Hemker HC, Culler BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody: potential implications for the effect of c7E3 Fab treatment on acute thrombosis and clinical restenosis J Clin Invest 1996;98:863-874.[ISI][Medline]
  22. Collet JP, Montalescot G, Lesty C, et al. Effects of abciximab on the architecture of platelet rich clots in patients with acute myocardial infarction undergoing primary coronary angioplasty Circulation 2001;103:2328-2331.[Abstract/Free Full Text]
  23. 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 J Am Coll Cardiol 1999;33:1528-1532.[Abstract/Free Full Text]
  24. Antman EM, Giugliano RP, 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.[Abstract/Free Full Text]
  25. The SPEED Group Strategies for Patency Enhancement in the Emergency Department (SPEED) GroupTrial of abciximab with and without low-dose reteplase for acute myocardial infarction. Circulation 2000;101:2788-2794.[Abstract/Free Full Text]
  26. ASSENT-4 Investigators Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomized trial Lancet 2006;367:569-578.[CrossRef][ISI][Medline]
  27. Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomized trials Lancet 2006;367:579-588.[CrossRef][ISI][Medline]
  28. Ellis SG, Armstrong P, Betriu A, et al. Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial Am Heart J 2004;147:E16.[CrossRef][Medline]
  29. Topol EJ. Toward a new frontier in myocardial reperfusion therapy: emerging platelet preeminence Circulation 1998;97:211-218.[Free Full Text]
  30. Roe MT, Ohman EM, Maas AC, et al. Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion J Am Coll Cardiol 2001;37:9-18.[Abstract/Free Full Text]
  31. Marzilli M, Sambuceti G, Testa R, Fedele S. Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina J Am Coll Cardiol 2002;40:2102-2109.[Abstract/Free Full Text]
  32. Aymong ED, Curtis MJ, Youssef M, et al. Abciximab attenuates coronary microvascular endothelial dysfunction after coronary stenting Circulation 2002;105:2981-2985.[Abstract/Free Full Text]
  33. Gawaz M, Neumann FJ, Dickfeld T, et al. Vitronectin receptor (avb3) mediates platelet adhesion to the luminal aspect of endothelial cells: implications for reperfusion in acute myocardial infarction Circulation 1997;96:1809-1818.[Abstract/Free Full Text]
  34. Lele M, Sajid M, Wajih N, Stouffer GA. Eptifibatide and 7E3, but not tirofiban, inhibit {alpha}vß3 integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin Circulation 2001;104:582-587.[Abstract/Free Full Text]
  35. Simon DI, Xu H, Ortlepp S, Rogers C, Rao NK. 7E3 monoclonal antibody directed against the platelet glycoprotein IIb/IIIa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1 Arterioscler Thromb Vasc Biol 1997;17:528-535.[Abstract/Free Full Text]
  36. Thompson RD, Wakelin MW, Larbi KY, et al. Divergent effects of platelet-endothelial cell adhesion molecule-1 ß3 integrin blockade on leukocyte transmigration in vivo J Immunol 2000;165:426-434.[Abstract/Free Full Text]



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