Skip Navigation



European Heart Journal Advance Access published online on November 7, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn480
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
30/1/33    most recent
ehn480v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ortolani, P.
Right arrow Articles by Branzi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ortolani, P.
Right arrow Articles by Branzi, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Long-term effectiveness of early administration of glycoprotein IIb/IIIa agents to real-world patients undergoing primary percutaneous interventions: results of a registry study in an ST-elevation myocardial infarction network

Paolo Ortolani1,*, Antonio Marzocchi1, Cinzia Marrozzini1, Tullio Palmerini1, Francesco Saia1, Nevio Taglieri1, Federica Baldazzi1, Gianni Dall'Ara1, Paola Nardini1, Silvia Gianstefani1, Paolo Guastaroba2, Roberto Grilli2 and Angelo Branzi1

1 Institute of Cardiology, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
2 Emilia-Romagna Regional Health Agency, Bologna, Italy

Received 4 January 2008; revised 3 September 2008; accepted 9 October 2008.

* Corresponding author. Tel: +39 051 636 4477, Fax: +39 051 344859, Email: paortol{at}tin.it


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Funding
 Acknowledgement
 References
 
Aims: To evaluate the clinical impact of early administration of glycoprotein IIb/IIIa agents (IIb/IIIa agents) in the context of a dedicated hub and spoke network allowing very prompt pharmacological/mechanical interventions.

Methods and results: Using a prospective database, we conducted a cohort study of ST-elevation myocardial infarction (STEMI) patients (n = 1124) undergoing primary percutaneous coronary interventions (PPCIs) and IIb/IIIa agents administration (period, 2003–2006). Comparisons were planned between patients receiving early IIb/IIIa agents administration (in hub/spoke centre emergency departments or during ambulance transfer; early group, n = 380) or delayed administration (in the catheterization laboratory; late group, n = 744). The primary outcome measure was long-term overall mortality/re-infarction. Baseline characteristics of the two groups were largely comparable. Angiographically, early group patients more often achieved pre-PPCI TIMI Grade 2–3 and TIMI Grade 3 flow. Clinically, the early administration group experienced lower 2-year risk of unadjusted mortality/re-infarction (17 vs. 23%; P = 0.01). After adjustment for potential confounders, early administration was associated with favourable outcome in the overall population (HR = 0.71, P = 0.03) and in high-risk subgroups (TIMI risk index >25, HR = 0.64, P = 0.02; Killip class >1, HR = 0.54, P = 0.01).

Conclusion: In patients treated by PPCI within a STEMI network setting, early administration of IIb/IIIa agents may provide long-term clinical benefits. Notably, these results appeared magnified in high-risk patients.

Key Words: Myocardial infarction • Percutaneous coronary interventions • Glycoprotein IIb/IIIa inhibitors


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Funding
 Acknowledgement
 References
 
Primary percutaneous coronary intervention (PPCI) is the preferred approach for re-establishing coronary perfusion in ST-elevation myocardial infarction (STEMI) when delivered in a timely fashion and in centres where appropriate facilities are available.1 Nevertheless, in many geographical areas, logistic considerations make it difficult to perform PPCI within the recommended 90 min from the first medical contact.2 The thrombus disaggregating effect of glycoprotein IIb/IIIa agents (IIb/IIIa agents) reduces the pre-PPCI thrombus burden, favours earlier culprit vessel reperfusion, and reduces the peri-procedural distal embolization.3–5 Randomized studies4,6 and a meta-analysis7 showed that IIb/IIIa agents therapy can improve the angiographic and clinical results of PPCI. Other studies showed that pre-treatment with IIb/IIIa agents (for 10–60 min) is associated with an initial TIMI 2–3 flow ranging from 35 to 55%.8–17 Owing to the delays encountered in many real-world settings, early administration of IIb/IIIa agents was proposed. However, the currently published randomized trials that endeavoured to evaluate this strategy showed conflicting angiographic and clinical results.8–21 We conducted a single-centre registry study (set in a hub and spoke STEMI network) to evaluate the effectiveness of a strategy of early administration of IIb/IIIa agents compared with the traditional (delayed) administration strategy.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Funding
 Acknowledgement
 References
 
Study design and setting
This retrospective cohort study (conceived in accordance with the principles of the most recent revision of the Declaration of Helsinki) was based on the database (at S. Orsola-Malpighi Hospital) of one of the two centralized PCI centres participating in the ‘Bologna STEMI hub and spoke network model'.22–25 Both centralized PCI intervention laboratories in the Province of Bologna (3702 km2, 950 000 inhabitants) are available at short notice on a 24 h basis within their hub-and-spoke catchment zones (containing a total of 10 peripheral hospitals without PCI facilities). Since June 2003, STEMI patients who call the ‘118 Emergency Medical Service’ from a location within about 90 min’ drive from a PCI centre are directly transported to the interventional laboratory after pre-hospital, ambulance-telemedicine diagnosis (thus bypassing the emergency department and the coronary care unit).22 Patients who present at the emergency department of a PCI centre (spontaneously or taken by ambulances not equipped for pre-hospital triage) are directly transferred to the interventional laboratory on diagnosis of STEMI. Patients admitted to the spoke centres of the STEMI network are transported to the nearest interventional laboratory on diagnosis of high-risk STEMI, although non-high risk patients generally receive thrombolytic treatment, some may also be directly referred to PPCI at the clinicians’ discretion. (Of note, patients who call the emergency service from locations >90 min drive from the interventional laboratory receive pre-hospital thrombolytic treatment.) The database used for the present study contains demographic information and comprehensive clinical, ECG, and procedural data concerning STEMI patients treated by PCI at the S. Orsola-Malpighi intervention laboratory. This prospectively compiled registry was approved by the Ethics Committees of the S. Orsola-Malpighi Hospital.

Eligibility criteria
The main inclusion criterion for this analysis was PPCI treatment associated with IIb/IIIa agent administration due to STEMI within 12 h of self-reported onset of symptoms from 2003 (when systematic use of PCI for STEMI patients was introduced) through 2006. Patients pre-treated with thrombolysis were excluded. There were no restrictions based on age, sex, or clinical status. Informed consent for PCI, participation in the study protocol and anonymous publication of scientific data, was systematically sought whenever possible.

Outcome measures
Comparisons were made between those patients who received early IIb/IIIa agents administration in hub/spoke centre emergency departments or during ambulance transfer (‘early administration group’) and patients submitted to the traditional delayed strategy of IIb/IIIa agents administration directly in the catheterization laboratory (‘late administration group’). The main clinical outcome measure was long-term freedom from death/re-infarction. A decision to perform subgroup analysis of patients with Killip class >1 and with TIMI risk index >25 (corresponding to the median value of the study population) was taken before the analysis.

Primary percutaneous coronary intervention protocol
Before arriving at the catheterization laboratory, all patients received aspirin (250 mg i.v.) and unfractioned heparin (5000 IU i.v.). The use of β-adrenergic blocking agents and nitrates during the PCI procedure was strongly encouraged. In the first 2 years of the provincial network (2003–2004), early administration of IIb/IIIa agents was mainly encouraged in patients transferred from spoke hospitals and in patients with large myocardial infarction (i.e. anterior myocardial infarction). Furthermore, until 2005, the lack of ambulance refrigeration facilities precluded administration of IIb/IIIa agents during pre-hospital triage. Since 2005, early administration has been more strongly encouraged in all settings. Thus, early administration of IIb/IIIa agents became more frequent during the study period: 24% (57/240) in 2003, 28% (85/302) in 2004, 41% (118/286) in 2005, and 41% (120/296) in 2006. The drugs administered were Abciximab [0.25 mg/kg as an intravenous bolus, followed by 0.125 µg/kg/min for 12 h (n = 966)] and Tirofiban [as a 10 µg/kg (n = 66) or 25 µg/kg (n = 92) intravenous bolus, always followed by 0.15 µg/kg/min for 18–24 h]. After PPCI, if a stent was deployed, patients were given a loading dose of 300 mg clopidogrel as soon as possible followed by a maintenance dose of 75 mg for at least 1 month (6–12 months for drug eluting stents).

Angiographic analysis and definitions
Quantitative coronary angiography was analysed by experienced site investigators blind to all data apart from the coronary angiogram. Culprit vessel TIMI flow grades were assessed before and after PPCI. Stratification of patients into ‘low risk’ and ‘non-low risk’ subsets was based on the presence of at least one of the main risk profile criteria proposed by TIMI investigators (age ≥70 years, anterior STEMI, heart rate ≥100 b.p.m. on admission).26 TIMI risk index was calculated using the equation:27 [heart rate in b.p.m. x (age in years/10)2]/systolic blood pressure in mmHg.

Cardiogenic shock (secondary to left or right ventricular dysfunction) was defined as a persistent systolic blood pressure <90 mmHg (recorded in the catheterization laboratory before PPCI or aortic balloon pump implantation), unresponsive to i.v. fluid administration, or requiring vasopressor agents to maintain systolic pressure ≥90 mmHg.28 Major bleeding was defined as the occurrence of intracranial or retroperitoneal bleeding or clinical signs of haemorrhage (including imaging), accompanied by a >5 g/dL drop in haemoglobin. Recurrent myocardial infarction was defined as a new increase in the creatinine kinase MB fraction to less than two times the normal upper limit, accompanied by chest pain and/or ECG changes. In-hospital events were: overall mortality, recurrent myocardial infarction, target vessel revascularization, stroke, and major bleeding. Long-term major cardiovascular events (MACE) were: overall mortality, recurrent myocardial infarction, and target vessel revascularization. Pain-to-balloon time (total ischaemic time) was defined as the interval (in min) between onset of symptoms and first balloon dilatation. Although left ventricular angiography was not performed, all patients received two-dimensional echocardiographic evaluations in the first 24 h after PPCI to assess left and right ventricular ejection fractions and exclude mechanical complications.

Ascertainment of events
For all patients, follow-up was closed on 30 September 2007. In-hospital outcome data were obtained from the main database, and by telephoning the peripheral hospitals to which patients had been transferred (as systematically recorded on the database). Long-term outcomes were ascertained by the Emilia-Romagna Regional Health Agency from codified Hospital Discharge Records (obligatorily archived for all public/private Italian hospitals) and Municipal Civil Registries. Hospital records were reviewed for additional information whenever deemed necessary.

Statistical analysis
Continuous data were expressed as mean ± SD or median (25th–75th percentiles), as appropriate, and categorical data as counts (percentages). Group comparisons of categorical variables were conducted using the {chi}2 test with Yates correction. The two-tailed Student's t-test was used to compare normally distributed continuous variables. Comparisons of non-normally distributed variables were conducted using the Mann–Whitney rank sum test. Estimated long-term outcome measures of the early and late IIb/IIIa agents administration groups were assessed by the Kaplan–Meier method and compared using the log-rank test. Cox proportional-hazard regression analysis was used to assess whether early IIb/IIIa agents administration was an independent predictor of long-term death/re-infarction (primary outcome measure) in the overall study population and in the pre-specified patients sub-groups (TIMI risk index >25 and Killip class >1). The models were created avoiding model building procedures and choosing 14 clinically relevant variables as: age (continuous variable), gender, diabetes, prior infarction, prior PCI, prior coronary artery bypass intervention, anterior infarction site, multivessel disease, left anterior descending coronary artery/left main trunk culprit vessel, β-blocker therapy, pain-to-balloon time >120 min, type of triage (ambulance, spoke hospital, or PPCI centre), year of enrolment, and advised duration of clopidogrel treatment (1 month vs. ≥6 months). These variables were directly and simultaneously inserted in the multivariable models. The proportional hazards assumption was tested for all variables on the basis of Schoenfeld residuals. To assess linearity, we categorized continuous variables (age) as intervals and performed the score test for trend of odds on the proportions of death/re-infarction at each interval. Analyses were conducted using SPSS for Windows, release 15.0 (SPSS Inc., Chicago, IL, USA). All P-values refer to two-tailed tests of significance; P < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Funding
 Acknowledgement
 References
 
Study population
During the study period, 1357 patients underwent PPCI at our institution within 12 h of symptoms without thrombolysis pre-treatment: of these, 1124 (83%) were treated with IIb/IIIa agents and were included in the present analysis. Early IIb/IIIa agents administration was performed in 380 (34%) patients (‘early administration group’), whereas the remaining 744 patients received IIb/IIIa agents in the catheterization laboratory immediately before PPCI (‘late administration group’). Table 1 summarizes patients’ clinical characteristics and risk factors according to the two treatment groups. In both groups of patients, pre-hospital triage accounted for ~30% of referrals (referral from spoke hospitals was more common in the early administration group, and PPCI–centre referral was more frequent in the late administration group). In line with these referral route distribution differences, the early administration group had somewhat longer ECG-to-laboratory and ECG-to-balloon times. Median pain-to-balloon time was ~3 h in both groups (13 min longer in the early administration group). Regarding drug exposure time, the interval between IIb/IIIa agents administration and PPCI was on average 58 min longer in the early administration group; at PPCI, patients in the early administration group had a slightly lower mean heart rate, higher mean systolic pressure, and consequently a lower median TIMI risk index value (Table 1). Table 2 summarizes patients’ angiographic and procedural characteristics in the two treatment groups.


View this table:
[in this window]
[in a new window]

  		Table 1 Patients' clinical characteristics and treatment delays (determined at catheterization laboratory arrival)

 

View this table:
[in this window]
[in a new window]

  		Table 2 Patients' angiographic and procedural characteristics

 
In-hospital findings
Pre-PPCI vessel patency was more frequent in the early administration group in terms of both TIMI Grade 3 (64/380, 17% vs. 81/744, 11%; P = 0.006) and 2–3 flow (128/380, 34% vs. 173/744, 23%; P = 0.0001) but no difference was apparent in the frequency of post-PPCI TIMI Grade 3 flow (338/380, 89% vs. 647/744, 87%; P = 0.51) or early left ventricular ejection fraction, as echo-detected within 24 h of PPCI (45 ± 11 vs. 45 ± 12%; P = 0.71). Table 3 reports frequencies of in-hospital events according to treatment, accompanied by univariate odds ratios for early administration, which showed a (non-significant) 43% reduction in in-hospital mortality. Notably, early administration showed no sign of being associated with excess major bleeding. Favourable associations in terms of reduced in-hospital mortality and adverse events (i.e. death, re-infarction, target vessel revascularization, stroke, or major bleeding) tended to be more apparent within ‘high-risk’ subgroups (TIMI risk index >25 or Killip class >1; Figure 1). At discharge, similar rates of concomitant medications were prescribed in both study groups: β-blockers were given in 93% of both the early (338/364) and late (643/691) IIb/IIIa agents administration groups (P = 0.99), statins in 57% of both the early (210/364) and late (394/691) IIb/IIIa agents administration groups (P = 0.96), and angiotensin-converting enzyme-inhibitors in respectively the 84% (306/364) and 82% (568/691) of the early and late IIb/IIIa agents administration groups (P = 0.50).


View this table:
[in this window]
[in a new window]

  		Table 3 In-hospital clinical adverse events according to IIb/IIIa treatment strategy

 

Figure 1
View larger version (22K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 In-hospital overall mortality and adverse events (defined as occurrence of any of the following events: overall mortality, re-infarction, target vessel revascularization, stroke, major bleeding) evaluated in high-risk patients sub-groups according to the IIb/IIIa treatment strategy.

 
Long-term outcome
Outcomes were ascertained for 1121 (99.7%) patients. Figure 2 reports Kaplan–Meier curves in the overall study population according to IIb/IIIa treatment strategy. During a median follow-up of 20 months (25th–75th percentile, 13–32), the early administration group showed lower estimated 2 year rates of all-cause mortality/re-infarction (17 vs. 23%; P = 0.01), all-cause mortality (11 vs. 15%; P = 0.02), and MACE (23 vs. 30%; P = 0.01). Differences were more apparent in the high-risk subgroups. Among patients with TIMI risk index >25 (n = 587), those who received early administration (n = 175) showed remarkably lower 2 year rates of death/re-infarction (23 vs. 33%; P = 0.02), overall mortality (16 vs. 25%; P = 0.02), and MACE (30 vs. 39%; P = 0.04) (Figure 3). Among patients with Killip class >1 (n = 265), the 2 year rates were 26 vs. 49% (P = 0.001) for mortality/re-infarction; 21% vs. 39% (P = 0.006) for overall mortality; 30% vs. 54% (P = 0.001) for MACE (Figure 4). At Cox multivariable regression analysis [adjusting for potential clinical, logistic, and procedural confounders (see above)], early administration of IIb/IIIa agents was associated with a significant reduction of death/re-infarction in the overall population (HR 0.71; 95% CI 0.53–0.96; P = 0.03). Significant reductions in death/re-infarction were recorded in both high-risk sub-groups: TIMI risk index >25 (HR 0.64; 95% CI 0.44–0.92; P = 0.02); Killip class >1 (HR = 0.54; 95% CI 0.33–0.88; P = 0.01).


Figure 2
View larger version (13K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 2 Kaplan–Meier curves for overall study population (n = 1124) according to primary percutaneous coronary intervention IIb/IIIa facilitation strategy: (A) overall mortality, (B) mortality/re-infarction, and (C) major cardiovascular events.

 

Figure 3
View larger version (14K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 3 Kaplan–Meier curves for TIMI risk index >25 sub-group (n = 587) according to primary percutaneous coronary intervention IIb/IIIa facilitation strategy: (A) overall mortality, (B) mortality/re-infarction, and (C) major cardiovascular events.

 

Figure 4
View larger version (14K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 4 Kaplan–Meier curves for Killip class >1 sub-group (n = 265) according to primary percutaneous coronary intervention IIb/IIIa facilitation strategy: (A) overall mortality, (B) mortality/re-infarction, and (C) major cardiovascular events.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Funding
 Acknowledgement
 References
 
This study, set in a highly organized hub and spoke STEMI network,22–25 regards unselected (and therefore mainly high risk) patients who underwent rapid IIb/IIIa agents administration and PPCI (coupled with a rather short average reperfusion time). The results suggest that a strategy of very early initiation of IIb/IIIa agents may indeed confer long-term clinical benefits in high-risk patients without any excess risk of major bleeding in hospital. The thrombus disaggregating effects of IIb/IIIa agents can reduce the pre-PPCI thrombus burden, favouring earlier culprit vessel reperfusion3–5 and, in line with previously reported studies,8–19 early administration of IIb/IIIa agents in our data was associated with higher proportions of patients achieving initial TIMI Grade 2–3 and 3 flow. Observational studies indicate that spontaneous initial TIMI 3 flow is associated with improved myocardial salvage and survival in STEMI patients.29,30 Early administration of IIb/IIIa agents is an attractive concept, the potential of which remains to be fully explored, at least in high-risk patients. A subgroup analysis of the ADMIRAL trial31 first suggested that abciximab might exert greater clinical efficacy when administered before arrival in the catheterization laboratory. Several small randomized studies8–17 of mainly non-high-risk patients showed that early IIb/IIIa agents administration can improve important surrogate endpoints. However, these studies were underpowered to test the clinical efficacy of the pharmacological improvements in vessel patency. Notably pooled analyses of randomized trials32–35 showed conflicting results and the recently concluded FINESSE trial20 failed to detect clinical benefits from IIb/IIIa agents facilitation therapy.

In our peculiar hub and spoke STEMI network setting, early administration of IIb/IIIa agents was associated with a substantial (26%) crude reduction in the long-term risk of death/re-infarction (accompanied by sizable reductions in long-term mortality and MACE) which also reached significance at Cox proportional hazards analysis. Remarkably, the favourable associations appeared more pronounced in high-risk subgroups (TIMI risk index >25, Killip class >1). These findings should be interpreted in the context of a high-risk population submitted to timely treatment in terms of both pharmacological administration and mechanical revascularization. The observation that outcome benefits appeared to occur more frequently in patients at higher risk may not be altogether surprising in the light of studies of conventional (i.e. non-early) IIb/IIIa agents administration: the only controlled trial where survival benefits were recorded allowed enrolment of high-risk STEMI patients;36 furthermore, some evidence of clinical benefit also emerged in a non-randomized study focusing on patients with cardiogenic shock.37 Notably, the American College of Cardiology/American Heart Association guidelines state that a strategy of facilitated PCI ‘holds promise’ (as a class IIb indication) in higher risk patients when PCI is not immediately available.38 In our STEMI network (inaugurated in 2003), implementation of standardized protocols allows fast inter-hospital transfers and—in the case of telemedicine-guided pre-hospital triage—emergency department bypass.22–25 In a significant number of our facilitated patients, IIb/IIIa agents administration and mechanical revascularization were completed in the early phase of ischaemia (within 3 h from the onset of pain): in other words, within the so-called ‘golden window’ when the clot is less resistant and myocardial salvage—and therefore the potential for clinical benefit—may be substantial.39 It is conceivable that the apparent discrepancy with the disappointing results of the FINESSE trial20 may be attributable to the different clinical and logistic characteristics of the two study populations [in our patients a more severe clinical picture, shorter times from pain-to-IIb/IIIa facilitation (126 vs. 165 min), from IIb/IIIa facilitation-to-revascularization (65 vs. 90 min), and from pain-to-revascularization (197 vs. 255 min)]. Finally, our findings are in line with the recently published On-TIME 2 trial that showed improvements in ST-segment resolution and 30 day clinical outcome in STEMI patients treated with very rapid pre-hospital administration of tirofiban21 and with the yet unpublished results (Dudek D, oral presentation, ESC 2007) of the EUROTRANSFER multicentre, prospective, registry (1086 patients) (ClinicalTrials.gov Identifier: NCT00378391 [ClinicalTrials.gov] ) that showed favourable in-hospital and 30 day clinical outcomes in transferred STEMI patients treated with early administration of abciximab and PPCI. Although vulnerable to hidden confounding factors and other sources of bias, this large single-centre registry study may help fill out the picture gained from the available randomized studies, suggesting relevant hypotheses for future studies. The characteristics of the two treatment groups were generally fairly well balanced. However, at admission to the catheterization laboratory, the early treatment group showed slight but significant differences in systolic pressure and heart rate, indicative of more stable haemodynamic state. Although these differences could largely be attributed to the benefits of early administration in severely affected patients, we cannot exclude that selection bias may also have played a role. The decision to administer IIb/IIIa agents early was left to the medical team performing the triage, and the treatment was more strongly encouraged for patients admitted through spoke hospitals and in the presence of anterior STEMI. Since observational studies are inherently vulnerable to selection bias and unidentified confounding, our results should be interpreted with some caution. This study focused on patients not receiving fibrinolytic therapy living (in the vast majority of cases) within 90 min drive of a PCI centre. Since transfer patients commonly undergo transport times in the 120 min range,40 it should be pointed out that the encouraging results of the present study may not be replicated in less favourable settings in which ambulance services are suboptimal or in regions in which transfer distances are unusually long. We think that small but adequately powered randomized studies focusing on high-risk patients in the state-of-the-art ‘rapid transfer’ networks where IIb/IIIa agents can be administered very promptly may be justified to test the hypothesis that facilitation is clinically beneficial in such favourable settings.


   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
Acknowledgement
 References
 
This study was supported by the Fanti Melloni Foundation.


   Acknowledgement
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 Acknowledgement
References
 
Robin M.T. Cooke provided writing assistance under contract with the University of Bologna.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 Acknowledgement
 References
 

  1. 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.[CrossRef][Web of Science][Medline]
  2. Nallamothu BK, Bates ER, Herrin J, Wang Y, Bradley EH, Krumholz HM. Times to treatment in transfer patients undergoing primary percutaneous coronary intervention in the United States: National Registry of Myocardial Infarction (NRMI)-3/4 analysis. Circulation (2005) 111:761–767.[Abstract/Free Full Text]
  3. Moser M, Bertram U, Peter K, Bode C, Ruef J. Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates. J Cardiovasc Pharmacol (2003) 41:586–592.[CrossRef][Web of Science][Medline]
  4. Neumann FJ, Blasini R, Schmitt C, Alt E, Dirschinger J, Gawaz M, Kastrati A, Schomig 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 infarction. Circulation (1998) 98:2695–2701.[Abstract/Free Full Text]
  5. 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]
  6. Antoniucci D, Rodriguez A, Hempel A, Valenti R, Migliorini A, Vigo F, Parodi G, Fernandez-Pereira C, Moschi G, Bartorelli A, Santoro GM, Bolognese L, Colombo A. 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]
  7. 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 trials. Jama (2005) 293:1759–1765.[Abstract/Free Full Text]
  8. van’t Hof AW, Ernst N, de Boer MJ, de Winter R, Boersma E, Bunt T, Petronio S, Marcel Gosselink AT, Jap W, Hollak F, Hoorntje JC, Suryapranata H, Dambrink JH, Zijlstra F. 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.[Abstract/Free Full Text]
  9. Lee DP, Herity NA, Hiatt BL, Fearon WF, Rezaee M, Carter AJ, Huston M, Schreiber D, DiBattiste PM, Yeung AC. 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.[Abstract/Free Full Text]
  10. Gabriel HM, Oliveira JA, da Silva PC, da Costa JM, da Cunha JA. Early administration of abciximab bolus in the emergency department improves angiographic outcome after primary PCI as assessed by TIMI frame count: results of the early ReoPro administration in myocardial infarction (ERAMI) trial. Catheter Cardiovasc Interv (2006) 68:218–224.[CrossRef][Web of Science][Medline]
  11. 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.[CrossRef][Web of Science][Medline]
  12. Cutlip DE, Ricciardi MJ, Ling FS, Carrozza JP Jr, Dua V, Garringer J, Giri S, Caputo RP. 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.[CrossRef][Web of Science][Medline]
  13. Gyongyosi M, Domanovits H, Benzer W, Haugk M, Heinisch B, Sodeck G, Hodl R, Gaul G, Bonner G, Wojta J, Laggner A, Glogar D, Huber K. 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 ReoPro-BRIDGING Study. Eur Heart J (2004) 25:2125–2133.[Abstract/Free Full Text]
  14. Zeymer U, Zahn R, Schiele R, Jansen W, Girth E, Gitt A, Seidl K, Schroder R, Schneider S, Senges J. Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial. Eur Heart J (2005) 26:1971–1977.[Abstract/Free Full Text]
  15. Maioli M, Bellandi F, Leoncini M, Toso A, Dabizzi RP. Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial). J Am Coll Cardiol (2007) 49:1517–1524.[Abstract/Free Full Text]
  16. Gibson CM, Kirtane AJ, Murphy SA, Rohrbeck S, Menon V, Lins J, Kazziha S, Rokos I, Shammas NW, Palabrica TM, Fish P, McCabe CH, Braunwald E. Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial. Am Heart J (2006) 152:668–675.[CrossRef][Web of Science][Medline]
  17. Rakowski T, Zalewski J, Legutko J, Bartus S, Rzeszutko L, Dziewierz A, Sorysz D, Bryniarski L, Zmudka K, Kaluza GL, Dubiel JS, Dudek D. 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. Am Heart J (2007) 153:360–365.[CrossRef][Web of Science][Medline]
  18. van den Merkhof LF, Zijlstra F, Olsson H, Grip L, Veen G, Bar FW, van den Brand MJ, Simoons ML, Verheugt FW. 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.[Abstract/Free Full Text]
  19. de Lemos JA, Antman EM, Gibson CM, McCabe CH, Giugliano RP, Murphy SA, Coulter SA, Anderson K, Scherer J, Frey MJ, Van Der Wieken R, Van De Werf F, Braunwald E. Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial. Circulation (2000) 101:239–243.[Abstract/Free Full Text]
  20. Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, Andersen HR, Betriu A, Savonitto S, Adamus J, Peruga JZ, Kosmider M, Katz O, Neunteufl T, Jorgova J, Dorobantu M, Grinfeld L, Armstrong P, Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med (2008) 358:2205–2217.[Abstract/Free Full Text]
  21. 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. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet (2008) 372:537–546.[CrossRef][Web of Science][Medline]
  22. Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Serantoni C, Aquilina M, Silenzi S, Baldazzi F, Grosseto D, Taglieri N, Cooke RM, Bacchi-Reggiani ML, Branzi A. Clinical impact of direct referral to primary percutaneous coronary intervention following pre-hospital diagnosis of ST-elevation myocardial infarction. Eur Heart J (2006) 27:1550–1557.[Abstract/Free Full Text]
  23. Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Baldazzi F, Silenzi S, Taglieri N, Bacchi-Reggiani ML, Gordini G, Guastaroba P, Grilli R, Branzi A. Usefulness of prehospital triage in patients with cardiogenic shock complicating ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Am J Cardiol (2007) 100:787–792.[CrossRef][Web of Science][Medline]
  24. Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Aquilina M, Baldazzi F, Silenzi S, Taglieri N, Grosseto D, Bacchi-Reggiani ML, Guastaroba P, Grilli R, Branzi A. Clinical comparison of ‘normal-hours’ vs ‘off-hours’ percutaneous coronary interventions for ST-elevation myocardial infarction. Am Heart J (2007) 154:366–372.[CrossRef][Web of Science][Medline]
  25. Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Taglieri N, Baldazzi F, Silenzi S, Bacchi-Reggiani ML, Guastaroba P, Grilli R, Branzi A. Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention. Eur Heart J (2008) 29:1241–1249.[Abstract/Free Full Text]
  26. Antoniucci D, Valenti R, Migliorini A, Moschi G, Trapani M, Buonamici P, Cerisano G, Bolognese L, Santoro GM. Relation of time to treatment and mortality in patients with acute myocardial infarction undergoing primary coronary angioplasty. Am J Cardiol (2002) 89:1248–1252.[CrossRef][Web of Science][Medline]
  27. Wiviott SD, Morrow DA, Frederick PD, Giugliano RP, Gibson CM, McCabe CH, Cannon CP, Antman EM, Braunwald E. Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: a simple index that predicts mortality in ST-segment elevation myocardial infarction. J Am Coll Cardiol (2004) 44:783–789.[Abstract/Free Full Text]
  28. Zeymer U, Vogt A, Zahn R, Weber MA, Tebbe U, Gottwik M, Bonzel T, Senges J, Neuhaus KL. Predictors of in-hospital mortality in 1333 patients with acute myocardial infarction complicated by cardiogenic shock treated with primary percutaneous coronary intervention (PCI); Results of the primary PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK). Eur Heart J (2004) 25:322–328.[Abstract/Free Full Text]
  29. De Luca G, Ernst N, Zijlstra F, van’t Hof AW, Hoorntje JC, Dambrink JH, Gosslink AT, de Boer MJ, Suryapranata H. Preprocedural TIMI flow and mortality in patients with acute myocardial infarction treated by primary angioplasty. J Am Coll Cardiol (2004) 43:1363–1367.[Abstract/Free Full Text]
  30. Stone GW, Cox D, Garcia E, Brodie BR, Morice MC, Griffin J, Mattos L, Lansky AJ, O’Neill WW, Grines CL. 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]
  31. Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P, Boulenc JM, Morice MC, Maillard L, Pansieri M, Choussat R, Pinton P. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med (2001) 344:1895–1903.[Abstract/Free Full Text]
  32. 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. J Am Med Assoc (2004) 292:362–366.[Abstract/Free Full Text]
  33. Godicke J, Flather M, Noc M, Gyongyosi M, Arntz HR, Grip L, Gabriel HM, Huber K, Nugara F, Schroder J, Svensson L, Wang D, Zorman S, Montalescot G. Early versus periprocedural administration of abciximab for primary angioplasty: a pooled analysis of 6 studies. Am Heart J (2005) 150:1015.[Medline]
  34. Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials. Lancet (2006) 367:579–588.[CrossRef][Web of Science][Medline]
  35. De Luca G, Gibson M, Bellandi F, Murphy S, Maioli M, Noc M, Zeymer U, Dudek D, Arntz HR, Zorman S, Gabriel M, Emre A, Cutlip D, Biondi-Zoccai G, Rakowski T, Gyongyosi M, Marino P, Huber K, Van’t Hof A. Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty (EGYPT) cooperation. An individual patients’ data meta-analysis. Heart (2008).
  36. 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 alone. Circulation (2004) 109:1704–1706.[Abstract/Free Full Text]
  37. Antoniucci D, Valenti R, Migliorini A, Moschi G, Trapani M, Dovellini EV, Bolognese L, Santoro GM. Abciximab therapy improves survival in patients with acute myocardial infarction complicated by early cardiogenic shock undergoing coronary artery stent implantation. Am J Cardiol (2002) 90:353–357.[CrossRef][Web of Science][Medline]
  38. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation (2004) 110:588–636.[Free Full Text]
  39. Gersh BJ, Stone GW, White HD, Holmes DR Jr. Pharmacological facilitation of primary percutaneous coronary intervention for acute myocardial infarction: is the slope of the curve the shape of the future? J Am Med Assoc (2005) 293:979–986.[Abstract/Free Full Text]
  40. Magid DJ, Wang Y, Herrin J, McNamara RL, Bradley EH, Curtis JP, Pollack CV Jr, French WJ, Blaney ME, Krumholz HM. Relationship between time of day, day of week, timeliness of reperfusion, and in-hospital mortality for patients with acute ST-segment elevation myocardial infarction. J Am Med Assoc (2005) 294:803–812.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
30/1/33    most recent
ehn480v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ortolani, P.
Right arrow Articles by Branzi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ortolani, P.
Right arrow Articles by Branzi, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?