|Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials.|
|Jump to Full Text|
|PMID: 19875386 Owner: NLM Status: MEDLINE|
|AIMS: Several randomized trials and a previous meta-analysis have shown significant benefits from Gp IIb-IIIa inhibitors, especially abciximab. Recent randomized trials (BRAVE-3 and HORIZON trials) have shown no benefits from adjunctive Gp IIb-IIIa inhibitors on the top of clopidogrel administration. However, the relatively low mortality may have hampered the conclusion of these recent trials. Thus, the aim of the current study was to perform an update meta-analysis of randomized trials on adjunctive Gp IIb-IIIa inhibitors in primary angioplasty, and to evaluate by meta-regression analysis, whether the results may be related to risk profile.
METHODS AND RESULTS: We obtained results from all randomized trials evaluating the benefits of adjunctive Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to September 2008. The following key words were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, Gp IIb-IIIa inhibitors, abciximab, tirofiban, and eptifibatide. Clinical endpoint was mortality at 30 days. Major bleeding complications were assessed as safety endpoint. No language restriction was applied. A total of 16 randomized trials were finally included in the meta-analysis, involving 10 085 patients (5094 or 50.5% in the Gp IIb-IIIa inhibitors group and 4991 or 49.5% in the control group. Gp IIb-IIIa inhibitors did not reduce 30 day mortality (2.8 vs. 2.9%, P = 0.75) or re-infarction (1.5 vs. 1.9%, P = 0.22), but were associated with higher risk of major bleeding complications (4.1 vs. 2.7%, P = 0.0004). However, we observed a significant relationship between patient's risk profile and benefits from adjunctive Gp IIb-IIIa inhibitors in terms of death (P = 0.008) but not re-infarction (P = 0.25).
CONCLUSION: This meta-analysis shows a significant relationship between benefits in mortality from Gp IIb-IIIa inhibitors and patient's risk profile. Thus, Gp IIb-IIIa inhibitors should be strongly considered among high-risk patients.
|Giuseppe De Luca; Eliano Navarese; Paolo Marino|
Related Documents :
|12184966 - Aspirin prophylaxis in patients at low risk for cardiovascular disease: a systematic re...
7749516 - Cardiogenic cerebral emboli: diagnosis and treatment.
11316916 - Benefit of adp receptor antagonists in atherothrombotic patients: new evidence.
17322926 - Evidence-based treatment recommendations for uremic bleeding.
3985036 - Relationship of psychologic factors to frequent symptomatic ventricular arrhythmia.
15302786 - Thin-filament-based modulation of contractile performance in human heart failure.
|Type: Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Review Date: 2009-10-28|
|Title: European heart journal Volume: 30 ISSN: 1522-9645 ISO Abbreviation: Eur. Heart J. Publication Date: 2009 Nov|
|Created Date: 2009-11-16 Completed Date: 2010-05-26 Revised Date: 2013-05-31|
Medline Journal Info:
|Nlm Unique ID: 8006263 Medline TA: Eur Heart J Country: England|
|Languages: eng Pagination: 2705-13 Citation Subset: IM|
|Division of Cardiology, Maggiore della Carità Hospital, Eastern Piedmont University A. Avogadro, Novara, Italy. firstname.lastname@example.org|
|APA/MLA Format Download EndNote Download BibTex|
Angioplasty, Balloon, Coronary*
Antibodies, Monoclonal / therapeutic use
Immunoglobulin Fab Fragments / therapeutic use
Myocardial Infarction / therapy*
Peptides / therapeutic use
Platelet Aggregation Inhibitors / therapeutic use*
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
Randomized Controlled Trials as Topic
Tyrosine / analogs & derivatives, therapeutic use
|0/Antibodies, Monoclonal; 0/Immunoglobulin Fab Fragments; 0/Peptides; 0/Platelet Aggregation Inhibitors; 0/Platelet Glycoprotein GPIIb-IIIa Complex; 0/eptifibatide; 144494-65-5/tirofiban; 55520-40-6/Tyrosine; X85G7936GV/abciximab|
|Eur Heart J. 2010 Mar;31(6):753-4
Journal ID (nlm-ta): Eur Heart J
Journal ID (publisher-id): eurheartj
Journal ID (hwp): ehj
Publisher: Oxford University Press
Published on behalf of the European Society of Cardiology. All rights reserved. ? The Author 2009. For permissions please email: email@example.com
Received Day: 27 Month: 10 Year: 2008
Revision Received Day: 21 Month: 9 Year: 2009
Accepted Day: 30 Month: 9 Year: 2009
Print publication date: Month: 11 Year: 2009
Electronic publication date: Day: 28 Month: 10 Year: 2009
pmc-release publication date: Day: 28 Month: 10 Year: 2009
Volume: 30 Issue: 22
First Page: 2705 Last Page: 2713
PubMed Id: 19875386
Publisher Id: ehp118
|Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials|
|Giuseppe De Luca*|
|Division of Cardiology, ?Maggiore della Carit?? Hospital, Eastern Piedmont University ?A. Avogadro?, Novara, Italy
|*Corresponding author. Tel: +39 0321 3733141, Fax: +39 0321 3733407, Email: firstname.lastname@example.org
Primary angioplasty has been shown to reduce mortality when compared with thrombolysis, due to the ability to restore TIMI 3 flow in the vast majority of patients.1 However, suboptimal reperfusion may be observed in a relatively large proportion of patients despite TIMI 3 flow, mainly due to no-reflow phenomenon and distal embolization.2 Large interest has been focused on the adjunctive administration of Gp IIb-IIIa inhibitors to improve perfusion and mortality. A previous meta-analysis of randomized trials3?16 has shown significant benefits in mortality and re-infarction.17 However, these benefits have disappeared in recent large randomized trials (BRAVE-3 and HORIZONS trials)18,19 conducted on the top of clopidogrel administration. However, the relatively low mortality may have hampered the conclusion of these recent trials. Thus, the aim of the current study was to perform an update meta-analysis of randomized trials on adjunctive Gp IIb-IIIa inhibitors in primary angioplasty, and to evaluate by meta-regression analysis, whether the results may be related to risk profile.
We obtained results from all randomized trials evaluating the benefits of adjunctive Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to September 2008. Furthermore, oral presentations and/or expert slide presentations were included [searched on the TCT (www.tctmd.com), EuroPCR (www.europcr.com), ACC (www.acc.org), AHA (www.aha.org), and ESC (www.escardio.org) websites from January 2002 to September 2008].The following key words were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, Gp IIb-IIIa inhibitors, abciximab, tirofiban, and eptifibatide.
Inclusion criteria were: (i) randomized treatment allocation; (ii) availability of complete clinical data. Exclusion criteria: (i) follow-up data in less than 90% of patients; (ii) ongoing studies or irretrievable data. No language restrictions were enforced.
Data were independently abstracted by two investigators. In case of incomplete or unclear data, authors, where possible, were contacted. Disagreements were resolved by consensus. Data were managed according to the intention-to-treat principle.
Primary and secondary endpoints were mortality and re-infarction at 30 days, respectively. Safety endpoint was the rate of major bleeding complications.
Statistical analysis was performed using the Review Manager 4.27, SPSS 15.0 statistical package and Comprehensive Meta-analysis Version 2. Odds ratio (OR) and 95% confidence intervals (95% CI) were used as summary statistics. The pooled OR was calculated by using a fixed-effect model with the Mantel?Haenszel method. The DerSimonian and Laird random effect model was additionally applied to calculate pooled OR in case of significant heterogeneity across studies. Between-study heterogeneity was analysed by means of I2 = [(Q ? df)/Q]?100%, where Q is the ?2 statistic, and df is its degrees of freedom. The potential publication bias was examined by constructing a ?funnel plot?, in which the standard error (SE) of the ln OR was plotted against the OR (30 day mortality).
The relationship between benefits in mortality and risk profile in each study (study level variable) was evaluated by a weighted random-effects meta-regression analysis regressing the log OR against the control group event rate expressed as odds using the inverse of the variance of the log OR as weight.20
We additionally performed a weighted random-effects meta-regression analysis regressing the log OR against the average log event rate observed in experimental and control group combined, using the inverse of the variance of the log OR as weight20 and a weighted random-effects meta-regression analysis regressing the log odds in the experimental group against the log odds in the control group, using the inverse of the variance of the log odds as weight.21
Results are reported as beta coefficients and two-sided P-values. Similar analysis was conducted for 30 day re-infarction.
The study was performed in compliance with the Quality of Reporting of Meta-Analyses (QUORUM) guidelines.22
Of the 859 potentially relevant articles initially screened, a total of 17 trials were initially identified3?16,18,19,23,24 (Figure?1). One trial4 was excluded because part of the ISAR trial.5 Thus, a total of 16 randomized trials3,5?16,18,19,23,24 were finally included in the meta-analysis., involving 10 085 patients (5094 or 50.5% in the Gp IIb-IIIa inhibitors group and 4991 or 49.5% in the control group). Characteristics of the included trials are shown in Table?1. High-dose bolus (600 mg) of clopidogrel was administrated in only three trials,19,23,24 whereas in the Horizons trial18 the dosage of bolus of clopidogrel was left to the discretion of the treating physicians. In the study by Zorman et al.,10 patients were randomized to early vs. late administration (in the cath lab) or no abciximab. In the Horizons trial,18 the control group received Bivalirudin as anticoagulation therapy instead of unfractionated heparin.
As shown in Figure?2, overall Gp IIb-IIIa inhibitors did not reduce 30 day mortality [2.8 vs. 2.9%, OR (95% CI) = 0.96 (0.76?1.22), P = 0.75, Phet = 0.48, NNT = 1000]. A trend in benefits in mortality was observed after the exclusion of the Horizons trial [2.6 vs. 3.3%, OR (95% CI)= 0.78 (0.58, 1.04), P = 0.09, Phet = 0.84; NNT = 143]. As shown in Figure?3, no publication biased was observed.
As shown in Figure?4A, we observed a relationship between patient's risk profile and mortality benefits from adjunctive Gp IIb-IIIa inhibitors (beta = ?14.12, P = 0.008; without Horizons: beta = ?10.31, P = 0.08). The relationship was confirmed when benefits were plotted against average events between experimental and control groups (beta = 0.68, P = 0.07; without Horizons: beta = ?0.47, P = 0.23) (Figure?4B). No significant relationship was observed between the odds of the experimental and control groups (beta = 0.23, P = 0.21; without Horizons: beta = 0.40, P = 0.06) (Figure?4C). In particular, the deviation of the regression line, corresponding to the pooled treatment effect, from the line of identity (Figure?4C) suggests heterogeneity and further supports the relationship between risk profile and mortality benefits.
As shown in Figure?5, overall Gp IIb-IIIa inhibitors did not reduce 30 day re-infarction [1.5 vs. 1.9%, OR (95% CI) = 0.82 (0.59?1.13), P = 0.22, Phet = 0.54; NNT = 250]. Similar findings were observed after the exclusion of the Horizons trial [1.3 vs. 1.9%, OR (95% CI) = 0.70 (0.46?1.08), P = 0.11, Phet = 0.5; NNT = 167].
As shown in Figure?6A, no significant relationship was observed between the risk of re-infarction and benefits from adjunctive Gp IIb-IIIa inhibitors (beta = ?17.88, P = 0.25; without Horizons: beta = ?10.31, P = 0.08). These data were confirmed when the benefits were plotted against average events between experimental and control groups (beta = ?0.10, P = 0.79; without Horizons: beta = ?0.47, P = 0.23) (Figure?6B). A significant relationship was observed between the odds of the experimental and control groups (beta = 0.55, P = 0.03; without Horizons: beta = 0.48, P = 0.12) (Figure?6C), with a minor deviation of the regression line from the line of identity when compared with that observed for mortality.
As shown in Figure?7, Gp IIb-IIIa inhibitors were associated with higher risk of major bleeding complications [3.9 vs. 2.6%, OR (95% CI) = 1.50 (1.19?1.89), P = 0.0005, Phet = 0.85]. Similar results were observed after exclusion of the Horizons trial [3.3 vs. 2.3%, OR (95% CI) = 1.41 (1.04, 1.93), P = 0.03, phet = 0.8].
The main finding of this meta-analysis is that among STEMI patients undergoing primary angioplasty, there is a significant relationship between risk profile and benefits from adjunctive Gp IIb-IIIa inhibitors in terms of mortality at 30 day follow-up.
Several randomized trials have shown that primary angioplasty is superior to thrombolysis. However, despite primary angioplasty is able to restore TIMI 3 flow in the vast majority of patients, a relatively large proportion of patients experience poor reperfusion.2 In the last years, growing interests have been focused on the role of distal embolization as major determinant of poor reperfusion.2 Gp IIb-IIIa inhibitors are the most powerful class of antiplatelet therapies, and their adjunctive beneficial effects have been shown in several randomized trials.
In the ACE trial,13 a total of 400 STEMI patients were randomized to abciximab or placebo, all patients treated with stent implantation. In this study, conducted without strict exclusion criteria, and thus with mortality rates close to daily clinical practice, abciximab was associated with a significantly improved survival and re-infarction. The benefits in mortality have been confirmed at long-term follow-up.25
Several recent large randomized trials have been conducted to explore the benefits from adjunctive Gp IIb-IIIa inhibitors on the top of clopidogrel administration, with contrasting results.18,19,23,24
In the BRAVE-3 trial,19 a total of 800 patients were randomized to abciximab or placebo before angioplasty, on the top of 600 mg. This study did not show benefits either in the primary endpoint (infarct size as estimated by scintigraphic techniques) or mortality (2.5 vs. 3.2%). It must be remarked that even though the aim of the study was to evaluate the impact of abciximab on infarct size, the median ischaemia time was 4.5 h. It may be arguable whether any adjunctive therapy in the late phase of ?golden hours? would provide adjunctive benefits in terms of infarct size. Furthermore, the risk profile was relatively low to evaluate the benefits in terms of clinical outcome.
In the large HORIZONS trial,18 3602 STEMI patients were randomized to heparin + Gp IIb-IIIa inhibitors were compared with bivalirudin. Patients received 300 or 600 mg clopidogrel loading dose (the decision was left to the physician's discretion). Bivalirudin was surprisingly associated with a mortality reduction, despite the significantly higher rate of acute in-stent thrombosis. As for the BRAVE-3 trial,19 a relatively low-risk population has been enrolled in this trial, that would have privileged bleeding complications over thrombotic complications. In the recent On-TIME-2 trial,21 a total of 985 patients were randomized on the top of 600 mg clopidogrel loading dose to early high-dose tirofiban vs. placebo (it was allowed periprocedural bail-out administration). Early tirofiban administration was associated with benefits in mortality (2.3 vs. 4%), even though the difference was not statistically significant due to the fact that the trials was underpowered to detect a significant reduction in mortality. However, by pooling data of 414 open-label patients (patients randomized in two Dutch centres as pilot phase) and 984 patients included in the double-blind study (with a total of 1398 patients) tirofiban administration was associated with reduced mortality (2.2 vs. 4.1%, P = 0.051).
In the current meta-analysis, we observed a significant relationship between risk profile and benefits in mortality, but not re-infarction, from adjunctive Gp IIb-IIIa inhibitors. Thus, since clopidogrel administration takes 3?4 h to reach the top of inhibition of platelet aggregation,26 Gp IIb-IIIa inhibitors should be considered to rapidly inhibit platelets, with subsequent benefits in mortality according to the risk profile. The use of risk scores, such as the TIMI Risk Score,27 should be strongly encouraged to identify a higher risk population with thrombotic complications largely outweighing the risk of bleeding complications, and thus who may subsequently benefit in terms of mortality from aggressive antithrombotic therapy.
Despite the negative results of the FINESSE trial,28 early administration may certainly be encouraged due to the benefits with early administration observed in the Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up (ADMIRAL) trial,7 and in several recent reports,29?31 including On-TIME 2 trial.23
The use of a risk score based on individual patient's data would have overcome the limitation due to the use of mortality in control group as marker of risk profile.19 In fact, the observed proportions of events in the control groups of the trials, as a measure of the underlying risk, may produce misleading results. This arises through a bias due to regression to the mean, especially observed in meta-analyses which include some small trials or in which the variability in the true underlying risks across trials is small. In order to minimize this limitation and to confirm initial findings, we have performed additional analyses thought to be more appropriate such as the use of average proportion of events in the control and treated groups as the measure of underlying risk or to plot the proportion of events in the treated group against that in the control group.20
Even though high-dose clopidogrel bolus may obtain a quicker and better platelet aggregation inhibition, the peak effect is still observed after 3?4 h,26 whereas Gp IIb-III inhibitors act very rapidly. In fact, benefits from Gp IIb-IIIa inhibitors were observed in the On-TIME 2 trial23 despite early administration of high-dose 600 mg clopidogrel, whereas in the BRAVE trial19 clopidogrel was administrated just before the procedure and thus less probably affecting the results of the study. However, due to paucity of data, no definite conclusion can be drawn on this issue. In addition, we analysed short-term outcomes, whereas some Gp IIb-IIIa inhibitor studies have demonstrated increased survival benefit with longer follow-up.25 No uniform definition of major bleeding complications was adopted in trials included in the current meta-analysis. Finally, we could not exclude a clinical heterogeneity between studies, due to different inclusion and exclusion criteria, and study drugs.
This meta-analysis shows a significant relationship between benefits in mortality from Gp IIb-IIIa inhibitors and patient's risk profile. Thus, Gp IIb-IIIa inhibitors should be strongly considered among high-risk patients.
Funding to pay the Open Access publication charges for this article was provided by Dipartimento di Medicine Clinica e Sperimentale, Eastern Piedmont University, Novara.
Conflict of interest: none declared.
|1.||Keeley EC,Boura JA,Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trialsLancetYear: 200361132012517460|
|2.||De Luca G,van't Hof AW,Ottervanger JP,Hoorntje JC,Gosselink AT,Dambrink JH,Zijlstra F,de Boer MJ,Suryapranata H. Unsuccessful reperfusion in patients with ST-segment elevation myocardial infarction treated by primary angioplastyAm Heart JYear: 200515055756216169340|
|3.||Brener SJ,Ban LA,Burchenal JEB,Katz S,George BS,Jones AA,Cohen ED,Gainey PC,White HJ,Cheek HB,Moses JW,Moliterno DJ,Effron MB,Topol EJ. on behalf of the RAPPORT investigatorsRandomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarctionCirculationYear: 1998987347419727542|
|4.||Neumann FJ,Blasini R,Schmitt C,Alt E,Dirschinger J,Gawaz M,Kastrati A,Sch?mig A. 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 infarctionCirculationYear: 199898269527019851955|
|5.||Neumann FJ,Kastrati A,Schmitt C,Blasini R,Hadamitzky M,Mehilli J,Gawaz M,Schleef M,Scyfarth M,Dirschinger J,Sch?mig A. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarctionJ Am Coll CardiolYear: 20003591592110732888|
|6.||Bolognese L. Effects of pre-treatment with abciximab on coronary artery patency and microcirculation in high risk patients with acute myocardial infarction eligible for primary angioplasty: results of the Abciximab patients evaluation (APE) randomized pilot study. CirculationYear: 200010Suppl. A150|
|7.||Montalescot G,Barragan P,Wittemberg O,Ecollan P,Elhadad S,Villain P,Boulenc JM,Morice MC,Maillard L,Pansi?ri M,Choussat R,Pinton P. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarctionN Engl J MedYear: 20013441895190311419426|
|8.||Stone G,Grines CL,Cox AD,Garcia E,Tcheng JE,Griffin JJ,Guagliumi G,Stuckey T,Turco M,Carroll JD,Rutherford BD,Lansky AJ. for the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) InvestigatorsComparison of angioplasty with stenting with or without abciximab, in acute myocardial infarctionN Engl J MedYear: 200234695796611919304|
|9.||Petronio AS,Musumeci G,Limbruno U,De Carlo M,Baglini R,Paterni G,Grazia Delle Donne M,Caravelli P,Nardi C,Mariani M. Abciximab improves 6-month clinical outcome after rescue coronary angioplastyAm Heart JYear: 200214333434111835040|
|10.||Zorman S,Zorman D,Noc M. Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplastyAm J CardiolYear: 20029053353612208418|
|11.||Lee CW,Moon DH,Hong MK,Lee JH,Choi SW,Yang HS,Kim JJ,Park SW,Park SJ. Effect of abciximab on myocardial salvage in patients with acute myocardial infarction undergoing primary angioplastyAm J CardiolYear: 2002901243124612450607|
|12.||Petronio AS,Rovai D,Musumeci G,Baglini R,Nardi C,Limbruno U,Palagi C,Volterrani D,Mariani M. Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplastyEur Heart JYear: 200324677612559938|
|13.||Antoniucci D,Migliorini A,Parodi G,Valenti R,Rodriguez A,Hempel A,Memisha G,Santoro GM. Abciximab-supported infarct artery stent implantation for acute myocardial infarction and long-term survival: a prospective, multicenter, randomized trial comparing infarct artery stenting plus abciximab with stenting aloneCirculationYear: 20041091704170615066943|
|14.||Ernst NM,Suryapranata H,Miedema K,Slingerland RJ,Ottervanger JP,Hoorntje JC,Gosselink AT,Dambrink JH,de Boer MJ,Zijlstra F,van 't Hof AW. Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarctionJ Am Coll CardiolYear: 2004441187119315364318|
|15.||Petronio AS,De Carlo M,Ciabatti N,Amoroso G,Limbruno U,Palagi C,Di Bello V,Romano MF,Mariani M. Left ventricular remodeling after primary coronary angioplasty in patients treated with abciximab or intracoronary adenosineAm Heart JYear: 2005150101516290987|
|16.||Steen H,Lehrke S,Wiegand UK,Merten C,Schuster L,Richardt G,Kulke C,Gehl HB,Lima JA,Katus HA,Giannitsis E. Very early cardiac magnetic resonance imaging for quantification of myocardial tissue perfusion in patients receiving tirofiban before percutaneous coronary intervention for ST-elevation myocardial infarctionAm Heart JYear: 200514956415864217|
|17.||De Luca G,Suryapranata H,Stone GW,Antoniucci D,Tcheng JE,Neumann FJ,van de Werf F,Antman EM,Topol EJ. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trialsJAMAYear: 20052931759176515827315|
|18.||Stone GW,Witzenbichler B,Guagliumi G,Peruga JZ,Brodie BR,Dudek D,Kornowski R,Hartmann F,Gersh BJ,Pocock SJ,Dangas G,Wong SC,Kirtane AJ,Parise H,Mehran R. HORIZONS-AMI Trial Investigators. Bivalirudin during primary PCI in acute myocardial infarctionN Engl J MedYear: 20083582218223018499566|
|19.||Mehilli J. Abciximab in Patients with AMI Undergoing Primary PCI after Clopidogrel Pretreatment: BRAVE-3 Trial http://www.clinicaltrialresults.com/.|
|20.||Sharp SJ,Thompson SG,Altman DG. The relation between treatment benefit and underlying risk in meta-analysisBMJYear: 19963137357388819447|
|21.||van Houwelingen HC,Arends LR,Stijnen T. Advanced methods in meta-analysis: multivariate approach and meta-regressionStat MedYear: 20022158962411836738|
|22.||Moher D,Cook DJ,Eastwood S,Olkin I,Rennie D,Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analysesLancetYear: 19993541896190010584742|
|23.||Van 't Hof AW,Ten Berg J,Heestermans T,Dill T,Funck RC,van Werkum W,Dambrink JH,Suryapranata H,van Houwelingen G,Ottervanger JP,Stella P,Giannitsis E,Hamm C. Ongoing Tirofiban In Myocardial Infarction Evaluation (On-TIME) 2 Study GroupPrehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trialLancetYear: 200837253754618707985|
|24.||Le May M. A Safety and Efficacy Study of Integrilin Facilitated PCI versus Primary PCI in ST Elevation Myocardial Infarction (ASSIST) http://www.clinicaltrialresults.com/.|
|25.||Montalescot G,Antoniucci D,Kastrati A,Neumann FJ,Borentain M,Migliorini A,Boutron C,Collet JP,Vicaut E. Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-upEur Heart JYear: 20072844344917251257|
|26.||Angiolillo DJ,Fern?ndez-Ortiz A,Bernardo E,Ram?rez C,Sabat? M,Ba?uelos C,Hern?ndez-Antol?n R,Escaned J,Moreno R,Alfonso F,Macaya C. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variabilityEur Heart JYear: 2004251903191015522469|
|27.||Morrow DA,Antman EM,Charlesworth A,Cairns R,Murphy SA,de Lemos JA,Giugliano RP,McCabe CH,Braunwald E. TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudyCirculationYear: 20001022031203711044416|
|28.||Ellis SG,Tendera M,de Belder MA,van Boven AJ,Widimsky P,Janssens LN,Andersen HR,Betriu A,Savonitto S,Adamus J,Peruga JZ,Kosmider M,Katz O,Neunteufl T,Jorgova J,Dorobantu M,Grinfeld L,Armstrong P,Brodic BR,Herrmann HC,Montalescot G,Neumann FJ,Effron MB,Barnathan ES,Topol EJ. FINESSE Investigators. Facilitated PCI in patients with ST-elevation myocardial infarctionN Engl J MedYear: 20083582205221718499565|
|29.||De Luca G,Gibson M,Bellandi F,Murphy S,Maioli M,Noc M,Zeymer U,Dudek D,Arntz HR,Zorman S,Gabriel HM,Emre A,Cutlip D,Biondi-Zoccai G,Rakowski T,Gyongyosi M,Marino P,Huber K,van 't Hof AW. Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty (EGYPT) cooperation. An individual patients' data meta-analysisHeartYear: 2008 [Epub ahead of print 5 June].|
|30.||Rakowski T,Siudak Z,Dziewierz A,Birkemeyer R,Legutko J,Mielecki W,Depukat R,Janzon M,Stefaniak J,Zmudka K,Dubiel JS,Partyka L,Dudek D. Early abciximab administration before transfer for primary percutaneous coronary interventions for ST-elevation myocardial infarction reduces 1-year mortality in patients with high-risk profile. Results from EUROTRANSFER registryAm Heart JYear: 20091585697519781416|
|31.||Huber K,Aylward PE,van't Hof AWJ,Montalescot G,Holmes DR,Betriu GA. Glycoprotein IIb-IIIa inhibitors before primary percutaneous coronary intervention of ST-Elevation myocardial infarction improve perfusion and outcomes: Insights from APEX-AMI. AbstractCirculationYear: 2007116II-673|
Characteristics of randomized trials included in the meta-analysis
|Study||Period||N||Study-drug design (number of patients)||Primary endpoint||Major bleeding complications|
|RAPPORT||1995?1997||483||Abciximab (n = 241) vs. placebo (n = 242)||6 month combined death, reMI, and TVR||TIMI major bleeding|
|APE||1997?1998||59||Early (n = 29) vs. no (n = 30) abciximab||Myocardial perfusion||n.r.|
|ADMIRAL||1997?1998||300||Stenting + abciximab (n = 151) vs. placebo (n = 149)||30 day combined death, reMI, urgent TVR||TIMI major bleeding|
|CADILLAC||1997?1999||2082||Abciximab + stent (n = 524) or balloon (n = 528), control + stent (n = 512), or balloon (n = 518)||6-month combined death, reMI, TVR, or disabling stroke||Not defined|
|Petronio et al.||1998?2000||89||Abciximab (n = 44) vs. placebo (n = 45)||6 month combined death, reMI, heart failure, TLR||Substantial haemodynamic compromise requiring treatment|
|ISAR-2||1997?1998||401||Stenting (n = 200) vs. abciximab + stenting (n = 201)||6 month angiographic restenosis||Intracranial haemorrhage, bleeding requiring surgery or transfusion|
|ACE||2001?2002||400||Stenting (n = 200) vs. abciximab + stenting (n = 200)||Combined death, reMI stroke, and target vessel||Stroke, bleeding requiring transfusion or vascular repair|
|Zorman et al.||1998?2001||163||Early (n = 56) vs. late (postangiography; n = 56) abciximab vs. placebo (n = 51)||Early (60 min) ST-segment resolution||Not defined|
|Petronio et al.||n.r||31||Abciximab (n = 17) vs. control (n = 14)||Myocardial perfusion and functional recovery at 30 days||TIMI major bleeding|
|Petronio et al.||n.r||90||Abciximab (n = 30) vs. adenosine (n = 30) vs. control (n = 30)||LV remodelling||GUSTO|
|Steen et al.||2000?2002||53||Tirofiban (n = 24) vs. control (n = 29)||Myocardial perfusion||n.r.|
|Ernst et al.||2002?2003||112||Abciximab (n = 28) or tirofiban (n = 29) or high-dose tirofiban (n = 28) vs. control (n = 27)||Platelet aggregation inhibition||Blood transfusion or surgery, intracranial or peritoneal haemorrhage|
|Lee et al.||n.r.||68||Abciximab (n = 32) vs. control (n = 36)||Myocardial salvage||n.r.|
|BRAVE-3||2004?2007||800||Abciximab (n = 401) vs. placebo (n = 399)||Infarct size||n.r.|
|HORIZONS-MI||2005?2007||3602||Glycoprotein IIb-IIIa inhibitors (n = 1800) vs. bivalirudine (n = 1802)||Net clinical outcome and major bleeding complications||TIMI major bleeding|
|On-TIME 2||2007?2008||984||Early high-dose tirofiban (n = 491) vs. placebo (n = 493)||Residual cumulative ST-deviation||TIMI major bleeding|
|ASSIST||2005?2008||400||Eptifibatide (n = 201) vs. placebo (n = 199)||Death, re-infarction, recurrent severe ischaemia at 30 days||TIMI major bleeding|
Abciximab dose: 0.25 mg/kg IV bolus followed by 12 h infusion at 0.125 mg kg?1 min?1. Eptifibatide dose: 2 boluses of 180 mg/kg IV 10 min apart, then 2.0 mg kg?1 min?1 infusion. Tirofiban: 10 ?g/kg bolus and 0.15 ?g/kg/min infusion over 24 h. High-dose tirofiban: bolus of 25 ?g/kg, followed by a 12 h infusion at 0.15 ?g/kg/min.
n.r., not reported; reMI, re-infarction; TVR, target vessel revascularization; LV, left ventricle.
Keywords: Primary angioplasty, Gp IIb-IIIa inhibitors, Meta-analysis, STEMI.
Previous Document: Matricide: A Critique of the Literature.
Next Document: Prevalence and risk factors related to infections of cardiac resynchronization therapy devices.