Early abciximab administration before primary percutaneous coronary intervention improves infarct-related artery patency and left ventricular function in high-risk patients with anterior wall myocardial infarction: A randomized study

doi:10.1016/j.ahj.2006.12.007

American Heart Journal

Volume 153, Issue 3, March 2007, Pages 360-365

https://doi.org/10.1016/j.ahj.2006.12.007 Get rights and content

Background

Early abciximab administration before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is recommended in practice guidelines. However, the evidence supporting abciximab use before and during transfer for PPCI is limited. We investigated the effect of early abciximab administration on early reperfusion, ST-segment resolution, enzymatic infarct size, and left ventricular function in patients with first anterior wall STEMI.

Methods

A total of 59 nonshock patients with STEMI admitted <12 hours to remote hospitals with anticipated delay to PPCI of <90 minutes were randomly assigned to 2 study groups: 27 patients received abciximab before transfer to catheterization laboratory (Early group), and 32 patients received abciximab immediately before PPCI (Late group).

Results

Angiography revealed more frequent infarct-related artery patency in the Early group than in the Late group (TIMI 2 + 3: 48% vs 20%, P = .04). Better ST-segment resolution of >50% 60 minutes after PPCI was found in Early group than in the Late group (84% vs 56.7%, P = .04). The area under the curve for creatine kinase–MB indicated a significantly greater extent of myocardial injury in the Late group versus the Early group (8324 ± 4185 vs 5938 ± 3949 U/L · h, P = .04). There was a significant difference in the 30-day left ventricular end-systolic volume index (P = .02) and end-diastolic volume index (P = .05) in the echocardiography favoring the Early group.

Conclusions

Early abciximab administration before transfer for PPCI in patients with first anterior wall STEMI results in more frequent infarct-related artery patency before PPCI, better myocardial tissue perfusion after PPCI, with lower enzymatic infarct size and lower degree of left ventricular remodeling during 30-day follow-up.

Section snippets

Methods

The study was approved by the institutional review board. All patients gave informed consent, and the study conformed to applicable institutional and national guidelines for research on human subjects, as well as to the Declaration of Helsinki.

The inclusion criteria were age >18 years, acute anterior wall STEMI (chest pain for >30 minutes, ST-segment elevation of >0.2 mV in at least 2 contiguous precordial leads), and admission within 12 hours from chest pain onset. The exclusion criteria were

Results

Fifty-nine patients were enrolled in the study. In 27 patients, abciximab was given in a community hospital before transportation (Early group), and 32 patients received the agent before PPCI in a catheterization laboratory (Late group). Four patients (2 in each group) were excluded from final analysis because of the absence of coronary artery stenosis in angiography. There were no significant differences in clinical and demographic characteristics between the study groups. Time from chest pain

Discussion

In the present study, early administration of abciximab before transportation for PPCI in high-risk patients with anterior myocardial infarction was associated with higher IRA patency rates before PPCI, better ST-segment elevation resolution after PPCI, with smaller extent of myocardial injury and reduced left ventricular remodeling at 30 days. These results emphasize the value of abciximab administration as an important adjuvant in patients undergoing PPCI.

Recent meta-analysis of studies

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Prehospital treatment with zalunfiban (RUC-4) in patients with ST- elevation myocardial infarction undergoing primary percutaneous coronary intervention: Rationale and design of the CELEBRATE trial
2023, American Heart Journal
Early and complete restoration of target vessel patency in ST-elevation myocardial infarction (STEMI) is associated with improved outcomes. Oral P2Y₁₂ inhibitors have failed to demonstrate either improved patency or reduced mortality when administered in the prehospital setting. Thus, there is a need for antiplatelet agents that achieve prompt and potent platelet inhibition, and that restore patency in the prehospital setting. Zalunfiban, a novel subcutaneously administered glycoprotein IIb/IIIa inhibitor designed for prehospital administration, has shown to achieve rapid, high-grade platelet inhibition that exceeds that of P2Y₁₂ inhibitors. Whether prehospital administration of zalunfiban can improve clinical outcome is unknown.
The present study is designed to assess the hypothesis that a single, prehospital injection of zalunfiban given in the ambulance, in addition to standard-of-care in patients with STEMI with intent to undergo primary percutaneous coronary intervention (PCI) will improve clinical outcome compared to standard-of-care with placebo.
The ongoing CELEBRATE trial (NCT04825743) is a phase 3, randomized, double-blinded, placebo-controlled, international trial. Patients with STEMI intended to undergo primary PCI will receive treatment with a single subcutaneous injection containing either zalunfiban dose 1 (0.110 mg/kg), zalunfiban dose 2 (0.130 mg/kg) or placebo, and the study drug will be administered in the ambulance before transportation to the hospital. A target of 2499 patients will be randomly assigned to one of the treatment groups in a 1:1:1 ratio, ie, to have approximately 833 evaluable patients per group. The primary efficacy outcome is a ranked 7-point scale on clinical outcomes. The primary safety outcome is severe or life-threatening bleeding according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria.
The CELEBRATE trial will assess whether a single prehospital subcutaneous injection of zalunfiban in addition to standard-of-care in patients with STEMI with intent to undergo primary PCI will result in improved clinical outcome.
S-nitrosylation of TRIM72 mends the broken heart: A molecular modifier-mediated cardioprotection
2014, Journal of Molecular and Cellular Cardiology
Pre-hospital diagnosis and transfer of patients with acute myocardial infarction - A decade long experience from one of Europe's largest STEMI networks
2013, Journal of Electrocardiology
Early reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) is essential. Although primary percutaneous coronary intervention (pPCI) is the preferred revascularization technique, it often involves longer primary transportation or secondary inter-hospital transfers and thus longer system related delays. The current ESC Guidelines state that PCI should be performed within 120 minutes from first medical contact, and door-to-balloon time should be < 60 minutes in order to reduce long term mortality. STEMI networks should be established with regionalization of pPCI treatment to address the challenges regarding pre-hospital treatment, triage and transport of STEMI patients and collaborations between hospitals and Emergency Medical Services (EMS).
We report on a regional decade long experience from one of Europe's largest STEMI networks located in Eastern Denmark, which serves a catchment area of 2.5 million inhabitants by processing ~ 4000 prehospital ECGs annually transmitted from 4 EMS systems to a single pPCI center treating 1100 patients per year.
This organization has led to a significant improvement of the standard of therapy for acute myocardial infarction (MI) patients leading to historically low 30-day mortality for STEMI patients (< 6%). About 70–80% of all STEMI patients are being triaged from the field and rerouted to the regional pPCI center. Significant delays are still found among patients who present to local hospitals and for those who are first admitted to a local emergency room and thus subject to inter-hospital transfer. In the directly transferred group, approximately 80% of patients can be treated within the current guideline time window of 120 minutes when triaged within a 185 km (~ 115 miles) radius. Since 2010, a Helicopter Emergency Medical Service has been implemented for air rescue. Air transfer was associated with a 20–30 minute decrease from first medical contact to pPCI, at distances down to 90 km from the pPCI center and with a trend toward better survival among air transported patients. The pPCI center also serves a small island in the Baltic Sea, where STEMI patients are rescued via air force helicopters. Based on data from more than 100 patients transferred over the past decade, we have found a similar in-hospital and long term mortality rate compared to the main island inhabitants.
In conclusion, with the optimal collaboration within a STEMI network including local hospitals, university clinics, EMS and military helicopters using the same telemedicine system and field triage of STEMI patients, most patients can be treated within the time limits suggested by the current guidelines. These organizational changes are likely to contribute to the improved mortality rate for STEMI patients.
Efficacy and safety of early versus late glycoprotein IIb/IIIa inhibitors for PCI
2013, International Journal of Cardiology
Citation Excerpt :
Clopidogrel treatment and early abciximab administration did not significantly improve LVEF on the basis of three relevant trials [21,24,27] (MD 0.03; 95% CI — 0.02 to 0.08; P = 0.2). Short-term mortality was available in two trials [24,31], at one month follow-up in 15 trials [19,20,25–30,32–38], and at three month follow-up in one trial [11]. No significant reduction in short-term mortality was observed with early abciximab (RR 1.00; 95% CI 0.69 to 1.43 P = 0.98) or SMGP (RR 1.57; 95% CI 0.89 to 2.77; P = 0.12) (Fig. 8) administration.
Glycoprotein (Gp) IIb/IIIa inhibitors are beneficial for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). However, optimal drug timing remains inconclusive. Therefore, this study was to perform a meta-analysis of the clinical efficiency and safety of early versus late GpIIb/IIIa inhibitors in STEMI patients undergoing PCI.
A comprehensive search was to identify randomized trials of early versus late GpIIb/IIIa inhibitors in STEMI patients undergoing PCI. The GpIIb/IIIa inhibitors were abciximab and small-molecular Gp inhibitors (SMGP) namely eptifibatide and tirofiban. The efficacy endpoints included pre-procedural Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, post-procedural TIMI 3 flow, complete ST-segment resolution, left ventricle ejection fraction (LVEF), and mortality. The safety endpoint was the occurrence of major bleeding complications.
Nineteen trials were included in the meta-analysis, involving 4209 patients (early 2124 versus late 2085). Early GpIIb/IIIa inhibitors significantly improved pre-procedural TIMI 3 flow, while early abciximab, but not SMGP, further enhanced post-procedural TIMI 3 flow, complete ST-segment resolution, LVEF, and reduced six-month mortality. In addition to clopidogrel loading, only early abciximab improved pre-procedural TIMI 3 flow and complete ST-segment resolution. The rate of major bleeding complications was not increased in early GpIIb/IIIa inhibitors with/without clopidogrel loading.
Early GpIIb/IIIa inhibitors improved pre-procedural TIMI 3 flow and early abciximab provided favorable clinical outcomes in STEMI patients undergoing PCI. On the basis of clopidogrel loading, early abciximab enhanced pre-procedural TIMI 3 flow and ST-segment resolution. These beneficial effects were achieved without increased risks of major bleeding complications.
Early abciximab administration before primary percutaneous coronary intervention improves clinical outcome in diabetic patients with ST-segment elevation myocardial infarction (EUROTRANSFER Registry)
2012, Atherosclerosis
Diabetes is an important determinant of prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Limited data are available concerning benefits and risks of upstream abciximab administration in diabetic patients. Thus, the objective of the study was to assess the impact of early abciximab administration before primary angioplasty (PCI) for STEMI in diabetic patients.
Data were gathered for 1650 consecutive STEMI patients transferred for primary PCI from hospital networks in seven countries in Europe from November 2005 to January 2007 (the EUROTRANSFER Registry population). Patients were stratified by diabetes mellitus presence and then by abciximab administration strategy (early – more than 30 min before PCI vs. late).
Diabetes mellitus was diagnosed in 262 (15.9%) patients. Patients with diabetes mellitus were high-risk individuals, with advanced age, higher prevalence of comorbidities and increased risk of ischemic events during follow-up in comparison to non-diabetic patients. A total of 1086 patients who received abciximab were identified. Strategy of early abciximab administration was associated with enhanced infarct-related artery patency before PCI, and improved epicardial flow after PCI in both diabetic and non-diabetic patients. Importantly, early abciximab in diabetic patients led to the decrease in ischemic events, including 30-day (OR 0.260, 95% CI 0.089–0.759, p = 0.012) and 1-year (OR 0.273, 95% CI 0.099–0.749, p = 0.012) mortality reduction. However, only a trend toward improved survival was confirmed after adjustment for potential confounders. On the contrary, the reduction of 30-day (OR 0.620, 95% CI 0.334–1.189, p = 0.16) and 1-year (OR 0.643, 95% CI 0.379–1.089, p = 0.10) mortality rates was not significant among non-diabetic patients.
Early administration of abciximab improves infarct-related artery patency before and after primary PCI, and leads to improved survival in diabetic STEMI patients.
Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead
2021, Thrombosis and Haemostasis

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Clinical InvestigationAcute Ischemic Heart DiseaseEarly abciximab administration before primary percutaneous coronary intervention improves infarct-related artery patency and left ventricular function in high-risk patients with anterior wall myocardial infarction: A randomized study

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Lancet

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

Am J Heart

J Am Coll Cardiol

Lancet

Int J Cardiol

Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials

JAMA

Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction

N Engl J Med

Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion—results of the Austrian multi-centre randomized RoePro-BRIDGING study

Eur Heart J

Prehospital versus periprocedural administration of abciximab in STEMI: early and late results from randomised REOMOBILE study

Eur Heart J

Clinical Investigation
Acute Ischemic Heart Disease
Early abciximab administration before primary percutaneous coronary intervention improves infarct-related artery patency and left ventricular function in high-risk patients with anterior wall myocardial infarction: A randomized study