Intracoronary Abciximab Research Articles

Intracoronary abciximab during PCI for STEMI

Intracoronary abciximab during PCI for STEMI

Retraction: Notice of unreliable findings

The aim of this study was to perform an individual patient-level pooled analysis of randomised trials, comparing intracoronary versus intravenous abciximab bolus use in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Abciximab represents a cornerstone in the treatment of STEMI patients undergoing primary PCI. Intracoronary abciximab bolus administration has been proposed as an alternative strategy to the standard intravenous route. However, whether intracoronary abciximab effectively improves clinical outcomes compared with standard route remains unknown. Individual data of 1198 patients enrolled in five trials were entered into the pooled analysis. The primary endpoint of the study was the occurrence of all-cause death and reinfarction at 30-day follow-up. Secondary endpoints were all-cause death, reinfarction and target-vessel revascularisation (TVR). No significant heterogeneity was found across trials. Compared with the intravenous route, intracoronary abciximab administration significantly reduced the risk of the composite of death and reinfarction (HR 0.52, 95% CI 0.29 to 0.94; p=0.03), death (HR 0.44, 95% CI 0.20 to 0.95; p=0.04) and TVR (HR 0.53, 95% CI 0.29 to 0.99; p=0.045), without a significant impact on the risk of reinfarction (HR 0.54, 95% CI 0.24 to 1.21; p=0.13). However, after correction for baseline differences, only the composite of death/reinfarction and death remained significant. In STEMI patients undergoing primary PCI, intracoronary abciximab administration, when compared with the intravenous standard route, can improve short-term clinical outcomes mainly by reducing the risk of death.

Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: A meta-analysis of 8 randomized trials

BackgroundAdjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over IV route. Therefore, the aim of the current study was to perform a meta-analysis of randomized trials (RCTs) to assess the clinical efficacy and safety of IC vs IV abciximab administration in STEMI patients undergoing primary angioplasty. MethodsWe obtained results from all RCTs enrolling STEMI patients undergoing primary percutaneous coronary intervention (PCI). The primary endpoint was mortality, while recurrent myocardial infarction, postprocedural epicardial (TIMI 3) and myocardial (MBG 2–3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications. ResultsA total of 8 randomized trials were finally included in the meta-analysis, enrolling a total of 3259 patients. As compared to IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR [95% CI]=1.76 [1.28–2.42], p<0.001), without significant benefits in terms of mortality (OR [95% CI]=0.85 [0.59–1.23], p=0.39), reinfarction (OR [95% CI]=0.79 [0.46–1.33], p=0.37), or major bleeding complications (OR [95% CI]=1.19 [0.76–1.87], p=0.44). However, we observed a significant relationship between patient's risk profile and mortality benefits from IC abciximab administration (p=0.011). ConclusionsThe present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow-up as compared to IV abciximab administration, without any excess of major bleedings in STEMI patients undergoing primary PCI. However, a significant relationship was observed between patient's risk profile and mortality benefits from IC abciximab administration. Therefore, waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended, but may be considered in high-risk patients.

Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial

Intracoronary administration of an abciximab bolus during a primary percutaneous coronary intervention results in a high local drug concentration, improved perfusion, and reduction of infarct size compared with intravenous bolus application. However, the safety and efficacy of intracoronary versus standard intravenous bolus application in patients with ST-elevation myocardial infarction (STEMI) undergoing this intervention has not been tested in a large-scale clinical trial. The AIDA STEMI trial was a randomised, open-label, multicentre trial. Patients presenting with STEMI in the previous 12 h with no contraindications for abciximab were randomly assigned in a 1:1 ratio by a central web-based randomisation system to intracoronary versus intravenous abciximab bolus (0·25 mg/kg bodyweight) during percutaneous coronary intervention with a subsequent 12 h intravenous infusion 0·125 μg/kg per min (maximum 10 μg/min). The primary endpoint was a composite of all-cause mortality, recurrent infarction, or new congestive heart failure within 90 days of randomisation. Secondary endpoints were the time to occurrence of the primary endpoint, each individual component of that endpoint, early ST-segment resolution, thrombolysis in myocardial infarction (TIMI) flow grade, and enzymatic infarct size. A masked central committee adjudicated the primary outcome and its components. Treatment allocation was not concealed from patients and investigators. This trial is registered with ClinicalTrials.gov, NCT00712101. Between July, 2008, and April, 2011, 2065 patients were randomly assigned intracoronary abciximab (n=1032) or intravenous abciximab (n=1033). Intracoronary, as compared with intravenous abciximab, resulted in a similar rate of the primary composite clinical endpoint at 90 days in 1876 analysable patients (7·0%vs 7·6%; odds ratio [OR] 0·91; 95% CI 0·64-1·28; p=0·58). The incidence of death (4·5%vs 3·6%; 1·24; 0·78-1·97; p=0·36) and reinfarction (1·8%vs 1·8%; 1·0; 0·51-1·96; p=0·99) did not differ between the treatment groups, whereas less patients in the intracoronary group had new congestive heart failure (2·4%vs 4·1%; 0·57; 0·33-0·97; p=0·04). None of the secondary endpoints or safety measures differed significantly between groups. In patients with STEMI undergoing primary percutaneous coronary intervention, intracoronary as compared to intravenous abciximab did not result in a difference in the combined endpoint of death, reinfarction, or congestive heart failure. Since intracoronary abciximab bolus administration is safe and might be related to reduced rates of congestive heart failure the intracoronary route might be preferred if abciximab is indicated. Lilly, Germany. University of Leipzig-Heart Centre. University of Leipzig, Clinical Trial Centre Leipzig, supported by the Federal Ministry of Education and Research (BMBF).

Meta-Analysis of Prospective Randomized Controlled Trials Comparing Intracoronary Versus Intravenous Abciximab in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Abciximab is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to improve outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention (pPCI). An earlier study reported better efficacy with intracoronary (IC) compared to intravenous (IV) administration, but this finding has not been duplicated in other studies, thus leaving a great deal of uncertainty as to the most efficacious route of administration. To investigate if IC abciximab compared to IV administration decreases mortality and major adverse cardiac events in patients with ST-segment elevation myocardial infarction who undergo pPCI, a meta-analysis was performed consisting only of prospective randomized controlled trials. Subgroup analysis was performed to investigate the source of difference in efficacy between the 2 strategies. A meta-analysis of 4 trials including 1,148 subjects revealed that IC abciximab significantly reduced mortality compared to IV administration (1.5% vs 3.6%, odds ratio 0.44, 95% confidence interval 0.20 to 0.95, p = 0.04). Major adverse cardiac events were also reduced in a subgroup in which <30% of patients received aspiration thrombectomy (6.1% vs 16.2%, odds ratio 0.33, 95% confidence interval 0.18 to 0.61, p = 0.0004). In conclusion, the totality of the data available from relatively small but high-quality studies shows a significant mortality reduction associated using IC abciximab for pPCI compared to IV abciximab. IC abciximab in the setting of pPCI for ST-segment elevation myocardial infarction may be beneficial for patients with higher risk profiles.

2011 Late-Breaking Clinical Trial/Clinical Science: Special Reports Abstracts

HomeCirculationVol. 124, No. 212011 Late-Breaking Clinical Trial/Clinical Science: Special Reports Abstracts Free AccessAbstractPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUB2011 Late-Breaking Clinical Trial/Clinical Science: Special Reports Abstracts Originally published22 Nov 2011https://doi.org/10.1161/CIR.0b013e31823c86a1Circulation. 2011;124:2365–23742011 Late-Breaking Clinical Trial/Clinical Science: Special Reports AbstractsSession Title: Late-Breaking Clinical Trials IIntracoronary Compared with Intravenous Bolus Abciximab Application During Primary Percutaneous Coronary Intervention: AIDA STEMI TrialHolger Thiele1, Jochen Wöhrle2, Rainer Hambrecht3, Harald Rittger4, Ralf Birkemeyer5, Bernward Lauer6, Petra Neuhaus7, Oana Brosteanu7, Peter Sick8, Marcus Wiemer9, Sebastian Kerber10, Ingo Eitel1, Klaus Kleinertz11, Gerhard Schuler11Herzzentrum Leipzig, Leipzig, Germany 2Univ of Ulm, Ulm, Germany 3Klnikum Links der Weser, Bremen, Germany 4Klnikum Coburg, Coburg, Germany 5Klnikum Villingen-Schwenningen, Villingen-Schwenningen, Germany 6Zentralklinik Bad Berka, Bad Berka, Germany 7KKSL, Leipzig, Germany 8Krankenhaus Barmherzige Brüder, Regensburg, Germany 9HERHerz- und Diabeteszentrum NRW, Bad Oeynhausen, Germany 10Herz- und Gefäβ-Klinik, Bad Neustadt, Germany 11Ambulantes Herzzentrum Chemnitz, Chemnitz, GermanyBackground: Intracoronary (IC) abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction in comparison to intravenous (IV) bolus application. Metaanalyses of randomized small to medium-sized trials suggest a reduction of death and reinfarction with the IC bolus application. The hypothesis of this trial is that IC abciximab bolus in comparison to standard IV application will improve the outcome of patients undergoing primary PCI in STEMI. Methods and Results: The AIDA STEMI study randomized 2072 STEMI patients at 27 tertiary centers in a 1:1 fashion from July 2008 to April 2011 to either IC or IV bolus abciximab administration during primary PCI with subsequent IV infusion for 12 h. The primary efficacy endpoint is the composite of all-cause mortality, recurrent infarction or new congestive heart failure within 90 days of randomization. Secondary clinical endpoints are each individual component of the endpoint within 90 days after randomization. Furthermore, ST-segment resolution and infarct size assessed indirectly by enzyme release are assessed. The trial is registered under www.clinicaltrials.gov: NCT00712101 and the study design has been published previously.1 Current patient characteristics showed no significant differences in baseline characteristics. The last clinical follow-up will be performed in the end of July 2011 and the final study results will be available during the Late Breaking Clinical Trial session. Conclusions: The AIDA STEMI study is the first adequately powered trial for clinical endpoints addressing important questions regarding efficacy and safety of IC versus IV abciximab bolus administration during primary PCI in patients with STEMI. The trial results will impact the route of glycoprotein IIb/IIIa-inhibitor administration.

Controlled Reperfusion with Intravenous Bivalirudin and Intracoronary Abciximab Combination Therapy in the Porcine Myocardial Infarction Model

IntroductionThe reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion. Materials and MethodsMyocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n=11) or saline (n=12) through the central lumen of an OTW catheter. All animals were followed for 48 hours. ResultsHistological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6±8% vs. 57.1±7%, p=0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p=0.07). ConclusionsDespite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab.

TCT-442: The Controlled Reperfusion with Bivalirudin and Intra Coronary Abciximab in the Porcine Mycoardial Infarction/Reperfusion Model

TCT-442: The Controlled Reperfusion with Bivalirudin and Intra Coronary Abciximab in the Porcine Mycoardial Infarction/Reperfusion Model

Platelet inhibition and GP IIb/IIIa receptor occupancy by intracoronary versus intravenous bolus administration of abciximab in patients with ST-elevation myocardial infarction

In patients with ST-elevation myocardial infarction (STEMI), direct intracoronary bolus administration of the glycoprotein (GP) IIb/IIIa receptor antagonist abciximab is associated with a reduction in infarct size, better myocardial salvage, less microvascular obstruction and improved myocardial blush grade as compared to intravenous bolus injection, presumably caused by higher local drug concentrations leading to a more pronounced inhibition of platelet aggregation. We investigated whether there are differences in the degree of GP IIb/IIIa receptor occupancy and platelet inhibition in blood drawn from the coronary sinus (CS) shortly after intracoronary versus intravenous abciximab bolus administration. A total of 16 patients with acute STEMI undergoing primary percutaneous coronary intervention within 12h of symptom onset underwent blood sampling from the CS before, immediately after and 30min after abciximab bolus administration (intracoronary bolus: n=8 patients; intravenous bolus: n=8 patients). Immediately after bolus application, GP IIb/IIIa receptor occupancy in CS blood was significantly higher in patients who received direct intracoronary bolus injection compared to administration via a peripheral vein (intracoronary bolus: 93.5% [IQR 92.7-95.4]; intravenous bolus: 74.0% [IQR 17.6-94.0], p=0.04). The degree of platelet inhibition was also markedly higher with intracoronary compared to intravenous dosing. At late sampling after 30min no significant differences were found between groups for both platelet reactivity and GP IIb/IIIa receptor occupancy. Acutely, direct intracoronary bolus injection resulted in a more pronounced local inhibition of platelet function and a higher degree of GP IIb/IIIa receptor occupancy as compared to standard intravenous bolus injection.

Clinical efficacy and safety of intracoronary vs. intravenous abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention: A meta-analysis of randomized trials

Adjunctive therapy with abciximab has been proven to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over the IV route. We aimed to perform a meta-analysis of randomized controlled trials to assess the clinical efficacy and safety of IC vs. IV abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). The primary endpoint was mortality, while recurrent myocardial infarction and target vessel revascularization (TVR) were selected as secondary endpoints. The safety endpoint was the risk of major bleeding complications. A total of six randomized trials were finally included in the meta-analysis, enrolling a total of 1246 patients. Compared to IV route, IC abciximab was associated with a significant reduction in mortality (odds ratio, OR [95% confidence interval (CI)] = 0.43 [0.20 − 0.94], p = 0.03), and TVR (OR [95% CI] = 0.53 [0.29 − 0.99], p = 0.05). No differences in terms of recurrent myocardial infarction (OR [95% CI] = 0.54 [0.23 − 1.28], p = 0.17) or major bleeding complications (OR [95% CI] = 0.91 [0.46 − 1.79], p = 0.79) were observed between the two strategies. The present meta-analysis showed that IC administration of abciximab is associated with significant benefits in mortality at short-term follow-up compared to IV abciximab administration, without any excess of major bleeding in STEMI patients undergoing PPCI. However, further trials are warranted to establish the optimal strategy of abciximab treatment in this setting.

580 Intracoronary abciximab during primary percutaneous coronary intervention is associated with reduced myocardial edema, myocardial hemorrhage and microvascular obstruction

580 Intracoronary abciximab during primary percutaneous coronary intervention is associated with reduced myocardial edema, myocardial hemorrhage and microvascular obstruction

Letter by Niccoli et al Regarding Article, “Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration: The Comparison of Intracoronary Versus Intravenous Abciximab Administration During Emergency Reperfusion of ST-Segment Elevation Myocardial Infarction (CICERO) Trial”

To the Editor: We read with great interest the article by Gu et al,1 who compared the effects of intracoronary abciximab versus intravenous administration on myocardial reperfusion in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration. They found that intracoronary administration of abciximab, compared with intravenous administration, did not improve the rate of successful myocardial reperfusion, as …

Rationale and design of the INFUSE-AMI study: A 2 × 2 factorial, randomized, multicenter, single-blind evaluation of intracoronary abciximab infusion and aspiration thrombectomy in patients undergoing percutaneous coronary intervention for anterior ST-segment elevation myocardial infarction

Whether thrombus aspiration and local glycoprotein IIb/IIIa administration reduce infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been established in multicenter studies. INFUSE-AMI is a multicenter, open-label, controlled, single-blind randomized study enrolling 452 subjects with anterior STEMI and an occluded proximal or mid-left anterior descending artery with thrombosis in myocardial infarction 0, 1, or 2 grade flow undergoing primary PCI with bivalirudin anticoagulation. Subjects are randomized in a 2 × 2 factorial to one of the following 4 arms: (1) local infusion of abciximab using the ClearWay RX Local Therapeutic Infusion Catheter (ClearWay, Atrium Medical Corp, Hudson, NH) after aspiration with a 6F Export Aspiration Catheter (Medtronic, Inc, Minneapolis, MN), (2) local infusion of abciximab using the ClearWay RX Infusion Catheter and no aspiration, (3) no local infusion of abciximab and aspiration with a 6F Export Aspiration Catheter, or (4) no local infusion of abciximab and no aspiration. The primary end point is infarct size (percentage of total left ventricular mass) at 30 days measured by cardiac magnetic resonance imaging. Other secondary end points include microvascular obstruction by cardiac magnetic resonance imaging at 5 days, ST-segment resolution, angiographic myocardial perfusion, thrombus burden, angiographic complications, and clinical events through 1-year follow-up. Safety end points include major and minor bleeding. INFUSE-AMI is testing the hypothesis that the intracoronary administration of an abciximab bolus with or without thrombus aspiration before stent implantation compared to no infusion with or without thrombus aspiration reduces infarct size among patients undergoing primary PCI for anterior STEMI who are treated with bivalirudin.

Intracoronary versus intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: 6-month effects on infarct size and left ventricular function

Administration of abciximab during primary percutaneous coronary intervention (PCI) reduces major adverse cardiac events (MACE) in patients with ST-elevation myocardial infarction (STEMI). Intracoronary (IC) abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction early after infarction. Aim of this study was to investigate whether the early benefits of an IC abciximab administration in STEMI patients undergoing PCI are sustained at 6 months. We performed 6-month follow-up of 154 STEMI patients undergoing PCI, who were randomised to either IC (n = 77) or intravenous (IV) (n = 77) bolus abciximab administration with subsequent 12-h intravenous infusion. The primary endpoint was infarct size at 6-month follow-up as assessed by delayed enhancement magnetic resonance imaging. Clinical end points were MACEs within 6 months after infarction. The median infarct size after 6 months was significantly reduced in the IC abciximab group (16.7 vs. 24.1%, p = 0.002). A significant recovery of LV function was only observed in the IC abciximab group (p < 0.001), and IC abciximab group patients had significantly less adverse remodelling as compared to standard IV abciximab treatment (p = 0.03). These beneficial effects also translated into a strong trend towards a reduced MACE rate in the IC abciximab group at 6-month follow-up (10 vs. 21%, p = 0.07). Intracoronary abciximab application in STEMI patients undergoing PCI is superior to standard IV treatment with respect to infarct size, recovery of LV function and reverse remodelling 6 months after infarction.

Aborted myocardial infarction in intracoronary compared with standard intravenous abciximab administration in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction

Backgound Abciximab reduces major adverse cardiac events (MACEs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary (IC) abciximab bolus application might be more effective than a standard intravenous (IV) bolus. So far the occurrence of aborted MI, a new therapeutic target of effective treatment in STEMI, has not been evaluated in IC versus IV abciximab administration in STEMI patients undergoing primary PCI. Methods To investigate the extent of aborted MI, 154 patients undergoing primary PCI were randomized to either IC (n = 77) or IV (n = 77) bolus abciximab administration with subsequent 12-hour intravenous infusion. For assessment of infarct size and extent of microvascular obstruction, all patients underwent late enhancement magnetic resonance imaging (MRI). Aborted MI was defined by major (≥ 50%) ST-segment resolution and a lack of subsequent cardiac enzyme rise ≥ 2 the upper normal limit. We also assessed the occurrence of true aborted MI defined as the absence of myocardial necrosis in MRI. Results The incidence of aborted MI was significantly higher in the IC group (p = 0.04); true aborted MI was only observed in the IC abciximab group (p = 0.01). At multivariable logistic regression analysis, IC abciximab application was a significant independent predictor of true aborted MI (p = 0.03). Aborted MI patients had an excellent prognosis at 6-month follow-up with no MACE as compared to 24 events in patients with non-aborted MI. Conclusions IC bolus application of abciximab in STEMI patients undergoing primary PCI results in a higher incidence of aborted MI and subsequent improved clinical outcome.

Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention: Design and rationale of the Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction (AIDA STEMI) trial

Intravenous abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction. The hypothesis of this trial is that abciximab bolus intracoronary in comparison to standard intravenous application will improve the outcome of patients undergoing primary PCI in STEMI. The Abciximab Intracoronary versus intravenously Drug Application in STEMI (AIDA STEMI) study is a 1,912-patient, prospective, multicenter, randomized, open-label, controlled trial. The study is designed to compare the efficacy and safety of intracoronary versus intravenous bolus abciximab administration during primary PCI with subsequent intravenous infusion for 12 hours. Patients will be randomized in a 1:1 fashion to 1 of the 2 treatments. The primary efficacy end point of AIDA STEMI is the composite of all-cause mortality, recurrent MI, or new congestive heart failure within 90 days of randomization. The primary safety outcome assessment will be major bleeding. The AIDA STEMI study addresses important questions regarding the efficacy and safety of intracoronary abciximab bolus administration during primary PCI in patients with STEMI, potentially optimizing the route of administration of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory.

Comparison between fixed-dose, intracoronary bolus-only versus standard weight-adjusted dose, intravenous bolus and infusion administration of abciximab in patients undergoing primary percutaneous coronary intervention

We studied the safety and effectiveness of fixed-dose, intracoronary bolus-only abciximab in 195 patients who underwent primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. The patients were divided into 2 groups: Group A (n=120, 61.5%) received fixed-dose, intracoronary bolus-only, abciximab 10 mg; and Group B (n=75, 38.5%) received standard intravenous bolus (0.25 mg/kg) and maintenance abciximab infusion of 0.125 μg/kg/min for 12 h. There was no statistically significant difference in the baseline and post-procedure TIMI flow between Groups A and B. Final TIMI 3 flow was achieved in 90.0% and 89.3% of the patients in Groups A and B, respectively (p=0.14). Final TIMI myocardial perfusion grade 2/3 was achieved in 92.5% and 96.0% of the patients in Groups A and B, respectively (p=0.45). The six-month clinical outcomes were similar between Groups A and B (8.3% versus 5.3%, p=0.62).

Delivery of Glycoprotein IIb/IIIa Inhibitor Therapy for Percutaneous Coronary Intervention

A major goal of any antithrombotic regimen administered during percutaneous coronary intervention (PCI) is the preservation of coronary microvascular perfusion, which is critical for myocardial survival. In addition to macrovascular thrombosis, microembolization into the downstream coronary artery bed that occurs during spontaneous plaque rupture and PCI plays a prominent role in the development of microvascular dysfunction that leads to myocardial infarction. In addition to physical obstruction of the lumen by the embolus, vasoconstriction and edema due to inflammation also impair microvascular flow.1 These events likely occur more frequently during PCI performed in the setting of unstable coronary syndromes.2 With Doppler guidewire technology, it was estimated that an average of 25 embolic events occurred during primary PCI for ST-segment elevation myocardial infarction.3 Article see p 784 Platelet aggregates are important components of coronary microemboli, along with leukocytes, erythrocytes, platelet-leukocyte aggregates, cholesterol crystals, and hyalin. Platelets and leukocytes within microemboli play a particularly important role in the pathophysiological changes of blood flow by promoting in situ microvascular thrombosis, vasoconstriction, and inflammation. Interestingly, the composition of the embolized material is similar in the settings of spontaneous and catheter-induced plaque rupture.1 In animal models, distal microembolization of inert microspheres is associated with an immediate reduction in flow due to vessel occlusion, followed by enhanced blood flow due to the effects of adenosine released from the embolized myocardium into the adjacent noninvolved myocardium.4 Microembolization results in overall reduced flow reserve and the progressive loss of contractile function, which often reverses within weeks. The degree of myocardial contractile dysfunction is disproportionate to the degree of infarction and is the result of inflammation.5 However, in the clinical condition, a more complex pathophysiology exists due to the influence of multiple components of the emboli. Platelets aggregate when fibrinogen binds to the active …

ClearWayRX System to reduce intracoronary thrombus in patients with acute coronary syndromes according to Optical Coherence Tomography after Abciximab Intracoronary Local infusion trial (COCTAIL): study rationale and design

Prompt reperfusion with percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes (ACS) improves clinical outcomes through salvage of myocardial tissue. Although use of intracoronary glycoprotein IIb/IIIa inhibition with PCI can result in improved rates of normal epicardial flow and myocardial perfusion, several unmet needs remain. The purpose of this trial is to evaluate the efficacy and safety of an intracoronary bolus of abciximab delivered using the ClearWayRX Therapeutic Perfusion Catheter followed by a dosing regimen of intravenous abciximab infusion after PCI, compared with intracoronary abciximab infusion, via the guiding catheter, followed by a dosing regimen of intravenous abciximab infusion after PCI in patients with ACS. Patients with ACS (either unstable angina/non-ST-elevation myocardial infarction or ST-elevation myocardial infarction with open infarct-related artery) and visible thrombus referred for PCI will be randomized to receive one of the two treatment regimens: local intracoronary infusion of abciximab through the ClearWayRX System or intracoronary infusion of abciximab via the guiding catheter. Both groups will receive intravenous infusion of abciximab during the 12-h period following the procedure. Optical coherence tomography assessment will be performed prior to abciximab administration and after the intracoronary infusions to document the change in the thrombus score. In addition, postintervention assessments of coronary microcirculatory function will be evaluated by means of the corrected thrombolysis in myocardial infarction frame count flow and the 'myocardial blush grade'. If local intracoronary infusion of abciximab through the ClearWayRX System significantly reduces thrombus burden, it will lend support to the use of this delivery system as a valuable tool in patients with ACS treated with PCI.

Intracoronary versus intravenous abciximab in ST-segment elevation myocardial infarction: rationale and design of the CICERO trial in patients undergoing primary percutaneous coronary intervention with thrombus aspiration

BackgroundAdministration of abciximab during primary percutaneous coronary intervention is an effective adjunctive therapy in the treatment of patients with ST-segment elevation myocardial infarction. Recent small-scaled studies have suggested that intracoronary administration of abciximab during primary percutaneous coronary intervention is superior to conventional intravenous administration. This study has been designed to investigate whether intracoronary bolus administration of abciximab is more effective than intravenous bolus administration in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration.Methods/DesignThe Comparison of IntraCoronary versus intravenous abciximab administration during Emergency Reperfusion Of ST-segment elevation myocardial infarction (CICERO) trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 530 patients with STEMI undergoing primary percutaneous coronary intervention are randomly assigned to either an intracoronary or intravenous bolus of weight-adjusted abciximab. The primary end point is the incidence of >70% ST-segment elevation resolution. Secondary end points consist of post-procedural residual ST-segment deviation, myocardial blush grade, distal embolization, enzymatic infarct size, in-hospital bleeding, and clinical outcome at 30 days and 1 year.DiscussionThe CICERO trial is the first clinical trial to date to verify the effect of intracoronary versus intravenous administration of abciximab on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration.Trial registrationClinicalTrials.gov NCT00927615