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==Clinical Trial Data==
==Clinical Trial Data==
===Facilitated PCI with a glycoprotein IIb/IIIa inhibitor alone===
===Facilitated PCI with a glycoprotein IIb/IIIa inhibitor alone===


The [[glycoprotein IIb/IIIa inhibitors]] such as the small molecules [[tirofiban]], and [[eptifibatide]] as well as the large molecule [[abciximab]] have been associated with improved outcomes in Primary PCI trials <ref name="pmid15827315">{{cite journal |author=De Luca G, Suryapranata H, Stone GW, ''et al'' |title=Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials |journal=JAMA |volume=293 |issue=14 |pages=1759–65 |year=2005 |month=April |pmid=15827315 |doi=10.1001/jama.293.14.1759 |url=}}</ref>  <ref name="pmid15265852">{{cite journal |author=Montalescot G, Borentain M, Payot L, Collet JP, Thomas D |title=Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis |journal=JAMA |volume=292 |issue=3 |pages=362–6 |year=2004 |month=July |pmid=15265852 |doi=10.1001/jama.292.3.362 |url=}}</ref>. The agents have also been evaluated in facilitated PCI trials where early administration of [[glycoprotein IIb/IIIa inhibitors]] in the emergency room (ER) has been compared with later administration in the cardiac catheterization laboratory.
The [[glycoprotein IIb/IIIa inhibitors]] such as the small molecules [[tirofiban]], and [[eptifibatide]] as well as the large molecule [[abciximab]] have been associated with improved outcomes in Primary PCI trials <ref name="pmid15827315">{{cite journal |author=De Luca G, Suryapranata H, Stone GW, ''et al'' |title=Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials |journal=JAMA |volume=293 |issue=14 |pages=1759–65 |year=2005 |month=April |pmid=15827315 |doi=10.1001/jama.293.14.1759 |url=}}</ref>  <ref name="pmid15265852">{{cite journal |author=Montalescot G, Borentain M, Payot L, Collet JP, Thomas D |title=Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis |journal=JAMA |volume=292 |issue=3 |pages=362–6 |year=2004 |month=July |pmid=15265852 |doi=10.1001/jama.292.3.362 |url=}}</ref>. The agents have also been evaluated in facilitated PCI trials where early administration of [[glycoprotein IIb/IIIa inhibitors]] in the emergency room (ER) has been compared with later administration in the cardiac catheterization laboratory.

Revision as of 15:55, 30 June 2010

Myocardial infarction
ICD-10 I21-I22
ICD-9 410
DiseasesDB 8664
MedlinePlus 000195
eMedicine med/1567  emerg/327 ped/2520

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

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Mechanism of Benefit

Among patients with ST elevation myocardial infarction, treatment with GPIIb/IIIa inhibitors has been associated with improved epicardial patency (TIMI 3 flow improves from approximately 15% to 30%) and improved myocardial perfusion on arrival to the cardiac catheterization laboratory [1]. Despite these improved rates of flow and perfusion, the isolated use of a GP IIb/IIIa inhibitor does not restore TIMI 3 flow in a sufficient proportion of patients to make it a viable stand alone pharmacologic strategy in the absence of adjunctive PCI. To improve the rate of normal TIMI grade 3 flow on arrival to the cardiac catheterization laboratory, GP IIb/IIIa antagonists have been combined with fibrinolytic agents.[2][3] Despite the improvement in epicardial vessel patency with the combination of these agents, clinical outcomes were not meaningfully improved [4] [5], and the combination of these agents prior to cardiac catheterization for STEMI has largely fallen out of favor.

Clinical Trial Data

Facilitated PCI with a glycoprotein IIb/IIIa inhibitor alone

The glycoprotein IIb/IIIa inhibitors such as the small molecules tirofiban, and eptifibatide as well as the large molecule abciximab have been associated with improved outcomes in Primary PCI trials [6] [7]. The agents have also been evaluated in facilitated PCI trials where early administration of glycoprotein IIb/IIIa inhibitors in the emergency room (ER) has been compared with later administration in the cardiac catheterization laboratory.

Facilitated PCI trials using tirofiban

The trials using tirofiban to facilitate PCI demonstrated significant improvement in the TFG 3 pre PCI but were not powered to demonstrate significant clinical benefit. The benefit of early administration of tirofiban compared to upstream administration was assessed in the TIGER-PA trial (TIrofiban Given in the Emergency Room before Primary Angioplasty). This study consisted of 100 patients who received tirofiban either in the ER or in the cath lab. There was a significant improvement in the initial angiographic parameters such as TIMI flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG). This study was not powered to demonstrate a significant clinical benefit [8].

Likewise, the investigators from the On-TIME trial (Ongoing Tirofiban in myocardial infarction Evaluation) evaluated a similar strategy of administration of tirofiban approximately one hour before PCI compared to administration of tirofiban in the cath lab [9]. This study also was not powered to demonstrate clinical benefit. However, the angiographic outcome of TFG 3 pre PCI was used as the primary endpoint which was not increased with the use of early tirofiban compared to upstream tirofiban (19% vs. 15%, p=0.22). In addition, an increase in combined TFG 2/3 flow, reduced thrombus burden and improved myocardial perfusion on angiography noted in the early group did not translate into improved angiographic outcome post PCI or on clinical outcomes.

In contrast to the above two studies, another small trial demonstrated that the use of tirofiban in the ER was not associated with a significant difference in the occurrence of TFG 2/3 compared to using tirofiban in the cath lab (39% vs. 27% p >0.2) but a trend towards better ST segment resolution was observed in the ER group (69% vs.77%, p=0.07) [10].

Facilitated PCI trials using abciximab

A more recent trial studied the benefit with the use of abciximab in the emergency room (ER) compared to upstream administration in the cath lab. The RELax-AMI study (Randomized Early versus Late abciximab in Acute Myocardial Infarction treated with primary coronary intervention) included 210 patients with acute ST segment elevation myocardial infarction. Of these 105 patients received abciximab in the ER and the remaining 105 received it in the cath lab. Similar to the TIGER-PA studies, this study demonstrated significant improvements in the pre-PCI angiographic parameters including TFG (grade 3 24% vs. 10%, p=0.01), corrected TIMI frame count (78±30 vs. 92±21, p=0.001) and myocardial blush grade (MBG 2/3) [15% vs. 6%, p=0.02] in the early abciximab group compared to the upstream group. The post-PCI ST segment resolution (>70%) was greater in the early abciximab group (50% vs. 35%, p=0.03) and the myocardial blush grade was also better (MBG 2/3 79% vs. 58%, p=0.001). The one month ejection fraction was significantly better in the early group [11].

Similarly, the ERAMI trial (Early Reopro Administration in Myocardial Infarction) demonstrated significant improvements in the post PCI CTFC and increased rate of TMPG 3 among patients who received abciximab in the ER compared to those who received it in the cath lab without any difference in angiographic parameters pre-PCI [12]. Similar to the ERAMI trial, Zorman et al demonstrated that administration of abciximab in the ER 12 hours before the procedure resulted in increased patency rates of the infarct related arteries. In addition there was also better ST segment resolution, and better survival compared to administration of abciximab in the cath lab or PCI without abciximab[13]. Likewise, the ReoPro- BRIDGING study also demonstrated that early administration of abciximab was associated with increased patency of infarct arteries and improved myocardial perfusion [14]. Another study using abciximab in the ER demonstrated not only an increased TFG 3 flow rate and improved TFC/MBG but also left ventricular function recovery compared to using abciximab in the cath lab [15].

Facilitated PCI using abciximab versus fibrinolysis

The use of enoxaparin in addition to a fibrinolytic and glycoprotein IIb/IIIa inhibitor was examined in another study which determined the safety and efficacy of administration of enoxaparin followed by tenecteplase (n=104) versus enoxaparin followed by abciximab and transfer for PCI (n=101). This study comparing glycoprotein IIb/IIIa facilitated PCI with fibrinolysis in the presence of enoxaparin in both groups did not demonstrate significant difference in ST segment resolution (>50%) at 120 minutes between the two groups (64% vs. 68%, p=NS). The TFG 3 (at 5-7 days after inclusion in the study) was present in 54% of cases in the fibrinolytic group compared to 71% of cases in the invasive group, p=0.04. There was only a trend towards clinical benefit (death, stroke and reinfarction) in the invasive group compared to the lytic group (3% vs. 8%, p=NS) despite the reduced symptom to treatment time in the fibrinolytic group compared to the invasive group (114 minutes vs. 202 minutes) [16].

Facilitated PCI trials using eptifibatide

Comparable to studies using tirofiban and abciximab, in the INTAMI study (INTegrilin in Acute Myocardial Infarction), Zeymer et al demonstrated that administration of eptifibatide in the ER was associated increased TFG 3 pre PCI compared to administration in the cath lab (34% vs. 10%, p=0.01) [17]. But there was no difference in the TFG 3 post-PCI, death, reinfarction, stroke and major bleed up to 30 days.

The TITAN TIMI-34 (Time to Integrilin Therapy in Acute Myocardial Infarction) was a larger trial than the INTAMI trial consisting of a total of 343 STEMI patients of which 180 received eptifibatide in the ER compared to 163 who received the drug in the cath lab. The primary endpoint, pre PCI corrected TIMI frame count was significantly better in the ER group compared to the cath lab group (77.5±32.2 vs. 84.3±30.7, p=0.049). The pre PCI TMPG 3 was more frequently seen in the ER group (24% vs. 14%, p=0.026). However there was no difference in the bleeding events and clinical outcomes between the two groups [1].

Facilitated PCI trials combining low dose fibrinolytic agent and glycoprotein IIb/IIIa inhibitor

Given the discrepancies in the outcomes in facilitated PCI using fibrinolytic alone and glycoprotein IIb/IIIa inhibitor alone, a strategy of combined therapy using low dose fibrinolytic and full dose glycoprotein IIb/IIIa inhibitor was examined. The Strategies for Patency Enhancement in the Emergency Department (SPEED-GUSTO-4 Pilot trial) examined the benefit of administration of fibrinolytic with or without abciximab among patients undergoing early PCI following an acute MI. This non randomized study demonstrated that administration of a half-dose reteplase and abciximab was safe and effective. This strategy was associated with TIMI flow grade 3 in 86% of cases at 90 minutes and the composite end point of death, reinfarction and urgent revascularization occurred in 5.6% of cases in the PCI group compared to 16% in those who did not undergo PCI[18].

The Alteplase and Tirofiban in Acute Myocardial Infarction (ATAMI), a small single centre study demonstrated that there was significantly high rates of TIMI grade 2/3 flow among STEMI patients randomized to combination therapy with 50mg alteplase and tirofiban prior to planned PCI compared to upstream administration of tirofiban in the catheter laboratory (87% vs. 42%, p<0.0001). These groups were compared with a matched control patients who underwent PCI with provisional abciximab in the cath lab (29% of patients had TIMI flow grade 2/3). The 30-day mortality was significantly lower in the combination therapy group compared to upstream tirofiban group and the control group (0.7% vs. 5.5%, p<0.02 vs. 6.3%). There were no differences in the incidence of bleeding events between the three groups[19]. This study has its limitations given the fact that this was a single center study with relatively small number of patients and a lower dose of tirofiban was used (10μg/kg).

Contrary to the SPEED and the ATAMI studies, the BRAVE (Bavarian Reperfusion Alternatives Evaluation) study by Kastrati and coworkers was an open label, randomized multicenter study in which the beneficial effect of the use of half dose reteplase and abciximab on the infarct size using single photon emission tomography (SPECT) was examined. The investigators did not demonstrate any improvement in the final infarct size using the combination therapy (n=125) compared to abciximab alone (n=128) among STEMI patients referred for PCI (mean difference in the infarct size was 1.3% between the two groups). There was no difference in the secondary endpoints such as death, reinfarction or stroke [20]. A similar strategy was examined in APAMIT (Asia Pacific Myocardial Infarction Trial) where all STEMI patients received abciximab and were randomized to either immediate PCI or to PCI sixty minutes later following the administration of alteplase. Like all previous studies this study demonstrated that facilitation with a lytic in addition to abciximab was associated with an increase TFG 3 pre PCI but no difference in the clinical outcomes[21].

Given the small sample size in the above studies, another randomized study, the ADVANCE-MI (ADressing the Value of facilitated Angioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction) study was designed to answer similar questions whether a strategy of combination fibrinolytic and a different glycoprotein IIb/IIIa inhibitor (eptifibatide) compared to eptifibatide + placebo prior to PCI would improve clinical outcomes. Although this study originally planned to recruit 5640 patients, it was prematurely terminated because of slow recruitment. An analysis of a total of 148 patients suggested that combination therapy (reduced dose tenecteplase and eptifibatide) was associated with improved epicardial flow and myocardial tissue perfusion on pre-PCI angiography. This strategy however resulted in a trend towards an increase in adverse outcomes (death, new/worsening heart failure or bleeding) compared to eptifibatide + placebo group[22].

The FINESSE trial (the largest trial on combination therapy) results were presented in the European Society of Cardiology meetings in 2007 (www.escardio.org). The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) study is a 3000-patient, prospective, multicenter, randomized, double-blind, placebo-controlled trial. The study was designed to compare the efficacy and safety of early administration of reduced-dose reteplase and abciximab combination therapy or abciximab alone followed by PCI with abciximab alone administered just before PCI for acute STEMI. Patients were randomized to one of the two facilitated PCI treatments or primary PCI in a 1:1:1 fashion[23]. At 90 days, there were no differences between treatment arms for the primary composite end points of the trial: all-cause mortality, readmission for heart failure, ventricular fibrillation, or cardiogenic shock [10.7% (PCI only group, n=806) vs. 10.5% (abciximab facilitated group, n=818) vs. 9.8% (reteplase and abciximab group, n=828)]. There were also no differences in all-cause mortality (4.5% vs. 5.5% vs. 5.2% respectively), complications of MI (8.9% vs. 7.5% vs. 7.4%), or any of the independent components of the primary composite end point. For safety end points, rates of TIMI major bleeding and minor bleeding were significantly higher for the abciximab/lytic facilitated PCI strategy as compared with primary PCI (14.5% vs. 6.9%, p<0.001). There was also a strong trend toward increased intracranial hemorrhage through discharge or day seven in the combined abciximab/lytic facilitation approach.

More recently, although not truly a facilitated PCI study, the CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction) study determined whether early transfer for PCI following pharmacotherapy administration improves outcomes compared to a conservative watchful waiting approach among patients with STEMI with anticipated delay in primary PCI due to their presentation to a non-PCI center[24]. Six hundred patients in this study were pretreated with aspirin, heparin, half dose reteplase and abciximab. Subsequently patients were randomized to either immediate transfer for PCI or transfer only in case of failed reperfusion or clinical deterioration. The investigators demonstrated that there was significant benefit in terms of reduction in 30-day mortality with the immediate transfer strategy (4.4% vs. 10.7%, p=0.004) without any differences in the bleeding events. It is important to note that the CARESS-in-AMI study determines whether early PCI improves pharmacotherapy outcomes. This is in contrast to the facilitated PCI strategy where pharmacotherapy is administered to improve PCI outcomes.

Dosing

Side Effects

ACC / AHA Guidelines- Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT)[25][26]

Class IIa

1. It is reasonable to start treatment with glycoprotein IIb/IIIa receptor antagonists (abciximab [Level of Evidence: A], tirofiban [Level of Evidence: B] or eptifibatide [Level of Evidence: B]) at the time of primary PCI (with or without stenting) in selected patients with STEMI.

Class IIb

1. The usefulness of glycoprotein IIb/IIIa receptor antagonists (as part of a preparatory pharmacological strategy for patients with STEMI before their arrival in the cardiac catheterization laboratory for angiography and PCI) is uncertain. (Level of Evidence: B)

ACC / AHA Guidelines- Combination Therapy With Glycoprotein IIb/IIIa Inhibitors (DO NOT EDIT)[25][26]

Class IIb

1. Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase may be considered for prevention of reinfarction (Level of Evidence: A) and other complications of STEMI in selected patients: anterior location of MI, age less than 75 years, and no risk factors for bleeding. In two clinical trials of combination reperfusion, the prevention of reinfarction did not translate into a survival benefit at either 30 days or 1 year. (Level of Evidence: B)

2. Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase may be considered for prevention of reinfarction and other complications of STEMI in selected patients: anterior location of MI, age less than 75 years, and no risk factors for bleeding in whom an early referral for angiography and PCI (i.e., facilitated PCI) is planned. (Level of Evidence: C)

Class III

1. Combination pharmacological reperfusion with abciximab and half-dose reteplase or tenecteplase should not be given to patients aged greater than 75 years because of an increased risk of ICH. (Level of Evidence: B)

Sources

  • The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction [27]
  • The 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction [28]
  • The 2009 ACC/AHA Focused update on the guidelines for STEMI and PCI[26]


References

  1. 1.0 1.1 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 (2006). "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". American Heart Journal. 152 (4): 668–75. doi:10.1016/j.ahj.2006.06.003. PMID 16996831. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  2. Antman EM, Giugliano RP, Gibson CM, McCabe CH, Coussement P, Kleiman NS, Vahanian A, Adgey AA, Menown I, Rupprecht HJ, Van der Wieken R, Ducas J, Scherer J, Anderson K, Van de Werf F, Braunwald E (1999). "Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators". Circulation. 99 (21): 2720–32. PMID 10351964. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  3. "Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group". Circulation. 101 (24): 2788–94. 2000. PMID 10859283. Unknown parameter |month= ignored (help)
  4. Topol EJ (2001). "Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial". Lancet. 357 (9272): 1905–14. PMID 11425410. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  5. Lincoff AM, Califf RM, Van de Werf F, Willerson JT, White HD, Armstrong PW, Guetta V, Gibler WB, Hochman JS, Bode C, Vahanian A, Steg PG, Ardissino D, Savonitto S, Bar F, Sadowski Z, Betriu A, Booth JE, Wolski K, Waller M, Topol EJ (2002). "Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial". JAMA : the Journal of the American Medical Association. 288 (17): 2130–5. PMID 12413372. Retrieved 2010-06-30. Unknown parameter |month= ignored (help)
  6. De Luca G, Suryapranata H, Stone GW; et al. (2005). "Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials". JAMA. 293 (14): 1759–65. doi:10.1001/jama.293.14.1759. PMID 15827315. Unknown parameter |month= ignored (help)
  7. Montalescot G, Borentain M, Payot L, Collet JP, Thomas D (2004). "Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis". JAMA. 292 (3): 362–6. doi:10.1001/jama.292.3.362. PMID 15265852. Unknown parameter |month= ignored (help)
  8. Lee DP, Herity NA, Hiatt BL; et al. (2003). "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. 107 (11): 1497–501. PMID 12654606. Unknown parameter |month= ignored (help)
  9. van 't Hof AW, Ernst N, de Boer MJ; et al. (2004). "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. 25 (10): 837–46. doi:10.1016/j.ehj.2004.04.003. PMID 15140531. Unknown parameter |month= ignored (help)
  10. Cutlip DE, Ricciardi MJ, Ling FS; et al. (2003). "Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction". Am. J. Cardiol. 92 (8): 977–80. PMID 14556878. Unknown parameter |month= ignored (help)
  11. Maioli M, Bellandi F, Leoncini M, Toso A, Dabizzi RP (2007). "Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial)". J. Am. Coll. Cardiol. 49 (14): 1517–24. doi:10.1016/j.jacc.2006.12.036. PMID 17418289. Unknown parameter |month= ignored (help)
  12. Gabriel HM, Oliveira JA, da Silva PC, da Costa JM, da Cunha JA (2006). "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. 68 (2): 218–24. doi:10.1002/ccd.20798. PMID 16817177. Unknown parameter |month= ignored (help)
  13. Zorman S, Zorman D, Noc M (2002). "Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty". Am. J. Cardiol. 90 (5): 533–6. PMID 12208418. Unknown parameter |month= ignored (help)
  14. Gyöngyösi M, Domanovits H, Benzer W; et al. (2004). "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. 25 (23): 2125–33. doi:10.1016/j.ehj.2004.09.018. PMID 15571828. Unknown parameter |month= ignored (help)
  15. Bellandi F, Maioli M, Leoncini M, Toso A, Dabizzi RP (2006). "Early abciximab administration in acute myocardial infarction treated with primary coronary intervention". Int. J. Cardiol. 108 (1): 36–42. doi:10.1016/j.ijcard.2005.04.025. PMID 15927285. Unknown parameter |month= ignored (help)
  16. Svensson L, Aasa M, Dellborg M; et al. (2006). "Comparison of very early treatment with either fibrinolysis or percutaneous coronary intervention facilitated with abciximab with respect to ST recovery and infarct-related artery epicardial flow in patients with acute ST-segment elevation myocardial infarction: the Swedish Early Decision (SWEDES) reperfusion trial". Am. Heart J. 151 (4): 798.e1–7. doi:10.1016/j.ahj.2005.09.013. PMID 16569536. Unknown parameter |month= ignored (help)
  17. Zeymer U, Zahn R, Schiele R; et al. (2005). "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. 26 (19): 1971–7. doi:10.1093/eurheartj/ehi293. PMID 15857851. Unknown parameter |month= ignored (help)
  18. Herrmann HC, Moliterno DJ, Ohman EM; et al. (2000). "Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial". J. Am. Coll. Cardiol. 36 (5): 1489–96. PMID 11079647. Unknown parameter |month= ignored (help)
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  20. Kastrati A, Mehilli J, Schlotterbeck K; et al. (2004). "Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial". JAMA. 291 (8): 947–54. doi:10.1001/jama.291.8.947. PMID 14982910. Unknown parameter |month= ignored (help)
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