“Rescue” Utilization of Abciximab for the Dissolution of Coronary Thrombus Developing as a Complication of Coronary Angioplasty

Objectives. This study sought to test the effect on thrombus score of the “rescue” utilization of the glycoprotein IIb/IIIa antagonist abciximab given to patients in whom intracoronary thrombus has developed as a complication after percutaneous transluminal coronary angioplasty (PTCA) and to determine its clinical utility.

Background. Abciximab is effective in the prevention of acute ischemic complications when given prophylactically to patients during high risk PTCA. However, its ability to therapeutically dissolve newly formed intracoronary thrombus occurring as a complication after PTCA is not known.

Methods. We performed an observational study in 29 consecutive patients who received abciximab (0.25 mg/kg body weight intravenous bolus, followed by a 12-h infusion at 10 μg/min) after attempted PTCA caused either the new development or further progression of thrombus. Angiograms were analyzed to determine thrombus score and Thrombolysis in Myocardial Infarction (TIMI) flow grade before and after abciximab. Procedural and clinical success and long-term outcome were also determined.

Results. Thrombus score decreased from 3.0 ± 0.9 (mean ± SD) to 0.86 ± 0.92 (p < 0.001), and TIMI flow grade increased from 2.5 ± 0.7 to 2.9 ± 0.3 (p = 0.008). No instances of distal embolization or no-reflow were noted. The procedural success (≤50% residual stenosis) rate was 97%. The clinical success (procedural success with no in-hospital myocardial infarction, bypass surgery or death) rate was 93%.

Conclusions. Dissolution of thrombus and restoration of TIMI grade 3 flow were readily achieved after administration of abciximab when delivered in a “rescue” manner after the development of thrombosis after PTCA. This novel use of abciximab will need to be validated in randomized trials.     

Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention

OBJECTIVES

The goal of this study was to test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h infusion reduces mortality after percutaneous coronary intervention (PCI); 2) if prevention of early myocardial infarction (MI) after PCI is a mechanism for reducing mortality; and 3) for risk factors for mortality after PCI.

BACKGROUND

Studies of PCI suggest that MI after intervention is predictive of mortality. Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced the incidence of MI among PCI patients in several trials. The presumed mechanism is prevention of platelet thrombus associated with vessel wall injury and downstream embolization into the microcirculation.

METHODS

In eight trials, 5,154 patients were randomized to a regimen comprising conventional therapy plus a bolus of abciximab within 1 h before PCI followed by a 12-h infusion; 4,136 controls were randomized to conventional therapy alone. Patient follow-up from six months to three years was available. Survival differences are examined using proportional hazards regression and survival curves.

RESULTS

A hazard ratio of 0.71 (95% confidence interval 0.57 to 0.89; P = 0.003) suggests a mortality benefit with abciximab. The absolute reduction in mortality was estimated to be 0.5% through 30 days, 0.7% through six months, 0.9% through one year and 1.8% through three years. Early MI explained 18% of the observed mortality benefit at one year. Multivariate regression suggests that patients with advanced cardiovascular disease may derive the greatest mortality benefit from abciximab.

CONCLUSIONS

The evidence from 9,290 randomized PCI patients shows a mortality benefit provided by abciximab bolus plus 12-h infusion.     

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.

OBJECTIVES: We sought to study the effect of early infusion of abciximab on coronary patency before primary angioplasty in patients with acute myocardial infarction. BACKGROUND: Glycoprotein IIb/IIIa antagonists have proved to be effective in reducing ischemic events associated with coronary angioplasty. The present study explores whether abciximab alone, without administration of thrombolytic therapy, may induce reperfusion in patients with acute myocardial infarction. METHODS: In the Glycoprotein Receptor Antagonist Patency Evaluation pilot study 60 patients with less than 6 h signs and symptoms of acute myocardial infarction eligible for primary angioplasty received in the emergency room a bolus of abciximab 250 microg/kg followed by a 12-h infusion of 10 microg/min. All patients were also treated with an oral dose of 160 mg aspirin and 5,000 IU of heparin intravenously. As soon as possible a diagnostic angiography was performed to evaluate the patency of the infarct-related artery. RESULTS: The median time between onset of symptoms and the administration of the abciximab bolus was 150 min (range 45 to 345), and the median time between abciximab bolus and first contrast injection in the infarct-related artery was 45 min (range 10 to 150). In 24 patients (40%, 95% confidence interval 28% to 52%) Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at a median time of 45 min (range 10 to 150) after abciximab bolus; TIMI flow grade 3 was observed in 11 patients (18%, 95% confidence interval 9% to 28%). There was no difference in percentage of TIMI flow grade 2 or 3 between patients who received abciximab within 2.5 h after onset of symptoms or thereafter. CONCLUSIONS: Abciximab therapy given in the emergency room in patients awaiting primary angioplasty is associated with full reperfusion (TIMI flow grade 3) in about 20% and with TIMI flow grade 2 or 3 in about 40% of the patients at a median time of 45 min. These figures are higher than those in primary angioplasty trials without such pretreatment. Randomized controlled trials of very early infusion of abciximab, either prehospital or in-hospital, in patients eligible for angioplasty are warranted.     

Feasibility and implications of an early discharge strategy after percutaneous intervention with abciximab in acute myocardial infarction (the CADILLAC Trial)

Early complications may hamper efforts to hasten discharge after primary percutaneous coronary intervention (PCI) for myocardial infarction (MI). Glycoprotein IIb/IIIa inhibitors, by reducing early recurrent ischemia, may aid in these efforts. We examined whether adjunctive abciximab could accelerate discharge and reduce costs within a trial of primary PCI after acute MI. The CADILLAC trial randomized 2,082 patients with MI to 1 of 4 reperfusion strategies in a 2 x 2 factorial design: angioplasty, angioplasty with abciximab, stent implantation, or stenting with abciximab. Patients randomized to abciximab had postprocedural heparin withheld, and discharge scheduled for days 1.5 to 2 (low-risk patients) or days 2 to 3 (high-risk patients) after MI if they were stable. Other patients were discharged at the physician's discretion. Abciximab treatment was associated with significant reductions in the primary end points of in-hospital death, reinfarction, ischemic target vessel revascularization (TVR), or disabling stroke (5.6% vs 2.7%, p = 0.003)--largely reflecting reduced ischemic TVR (3.8% vs 1.4%, p = 0.002)--and in early subacute thrombosis (1.3% vs 0.2%, p = 0.01). Hospitalization was significantly shorter in abciximab-treated patients (median 3.1 vs 3.5 days, p <0.001), but total in-hospital costs did not differ significantly (13,413 +/- 5,309 US dollars vs 13,000 +/- 6,006 US dollars, p = 0.13). Rates of the composite end point did not differ significantly during the week after discharge (0.8% vs 0.2%, p = 0.10), nor did component event rates. Abciximab during primary PCI is associated with fewer early adverse outcomes, likely contributing to offset its cost. Hospitalizations after primary PCI are so short, however, that efforts to accelerate discharge with abciximab appear unfeasible, and overall costs remain unchanged.     

Routine pretreatment with abciximab versus standard periprocedural therapy in mechanically ventilated cardiogenic shock patients undergoing primary percutaneous coronary intervention: Subanalysis of the PRAGUE-7 study

BACKGROUND:

The clinical outcome of patients with myocardial infarction (MI) complicated by cardiogenic shock (CS) who require mechanical ventilation (MV) is poor.

OBJECTIVE:

To analyze the impact of abciximab pretreatment in this high-risk population of MI patients.

METHODS:

The present study was a retrospective subanalysis of the multicentre randomized Routine Upfront Abciximab Versus Standard Peri-Procedural Therapy in Patients Undergoing Percutaneous Coronary Intervention for Cardiogenic Shock (PRAGUE-7) study, which included 80 MI patients in CS undergoing primary percutaneous coronary intervention (PCI). Patients were randomly assigned into group A (routine pretreatment with an abciximab bolus followed by a 1 h abciximab infusion) and group B (standard therapy). The subanalysis included 37 patients requiring MV. Seventeen patients were in group A and 20 were in group B. The primary end point (death/stroke/reinfarction/new severe renal failure) at 30 days, procedural success (thrombosis in myocardial infarction [TIMI] flow) and frequency of bleeding were assessed. The χ² and Student’s t tests were used for statistical analysis; P<0.05 was considered to be statistically significant.

RESULTS:

The primary end point occurred in nine (53%) patients in group A and 12 (60%) patients in group B (P=0.66). TIMI flow after primary PCI was higher in group A (2.75 versus 2.31; P<0.05). Major bleeding occurred in 12% of patients in group A versus 10% of patients in group B (P=0.86). Minor or minimal bleeding was more common in group A (29%) compared with group B (5%; P<0.05).

CONCLUSION:

The results of the present study suggest that routine pretreatment with abciximab before primary PCI in mechanically ventilated patients with MI complicated by cardiogenic shock was associated with better angiographic results but also with a higher incidence of bleeding.     

Evidence for Prevention of Death and Myocardial Infarction With Platelet Membrane Glycoprotein IIb/IIIa Receptor Blockade by Abciximab (c7E3 Fab) Among Patients With Unstable Angina Undergoing Percutaneous Coronary Revascularization

Objectives. We sought to evaluate whether patients with unstable angina undergoing coronary intervention derive particular clinical benefit from potent platelet inhibition.Background. Plaque rupture and platelet aggregation are pathogenetic processes common to unstable angina and ischemic complications of percutaneous coronary intervention.Methods. Of the 2,099 patients undergoing a coronary intervention in the Evaluation of 7E3 in Preventing Ischemic Complications (EPIC) trial, 489 were enrolled with the diagnosis of unstable angina and randomized to receive placebo, an abciximab (c7E3) bolus immediately before the intervention or an abciximab bolus followed by a 12-h infusion. The primary end point was a composite of death, myocardial infarction (MI) or urgent repeat revascularization within 30 days of randomization. The occurrence of death, MI or any revascularization within 6 months was also assessed.Results. Compared with placebo, the bolus and infusion of abciximab resulted in a 62% reduction in the rate of the primary end point (12.8% vs. 4.8%, p = 0.012) among patients with unstable angina, due primarily to a reduction in the incidences of death (3.2% vs. 1.2%, p = 0.164) and MI (9% vs. 1.8%, p = 0.004). By 6 months, cumulative death and MI were further reduced by abciximab (6.6% vs. 1.8%, p = 0.018 and 11.1% vs. 2.4%, p = 0.002, respectively). The magnitude of the risk reduction with abciximab was greater among the patients with unstable angina than among other patients in the EPIC trial without unstable angina for the end points of death (interaction: p = 0.008 at 30 days, p = 0.002 at 6 months) and MI (interaction: p = 0.004 at 30 days, p = 0.003 at 6 months).Conclusions. The syndrome of unstable angina identifies patients who will experience particularly marked reductions in the risk of death and MI with abciximab during coronary intervention.(J Am Coll Cardiol 1997;30:149–56)     

Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty.

AIM: To investigate the effect of abciximab on microvascular integrity and left ventricular (LV) functional recovery in patients with acute myocardial infarction (MI) treated by primary coronary angioplasty (PTCA). METHODS AND RESULTS: Thirty-one patients (27 males; age 39-76 years) with first, acute MI (<6 h after onset) were randomized to receive either abciximab+primary PTCA (n=17) or primary PTCA alone (n=14). Baseline characteristics of the two groups were similar. Myocardial reperfusion was studied shortly after PTCA by corrected TIMI frame count (cTFC) and intracoronary myocardial contrast echocardiography (MCE), after 48 h by intravenous MCE using intermittent, harmonic power Doppler, and after 1 month by intravenous MCE and 99 mTc-tetrofosmin SPECT. The patients treated with abciximab showed a shorter cTFC (23+/-4 vs 30+/-9 frames; P<0.05), a more preserved microvascular integrity shortly after PTCA (77% vs 55%; P<0.01), after 48 h (86% vs 50%; P<0.005) and at 1-month follow-up (86% vs 54% by MCE, P<0.001, and 68% vs 60% by SPECT, P<0.005) than patients treated with PTCA alone. Abciximab patients also showed a better recovery of LV function, as demonstrated by greater reduction in wall motion score index (1.4+/-0.3 vs 1.5+/-0.2; P<0.05) and increase in LV ejection fraction (53+/-7% vs 48+/-5%; P<0.001). CONCLUSIONS: Abciximab improves microvascular perfusion and LV functional recovery in primary PTCA.     

The benefit of abciximab in percutaneous coronary revascularization is not device-specific

Abciximab has been shown to decrease adverse outcomes after percutaneous coronary interventions, but it is unclear whether this beneficial effect is more or less pronounced with specific devices. This study sought to determine the relative magnitude of the benefit of abciximab among different interventional devices. Data from the 5 placebo-controlled trials of abciximab during coronary intervention were pooled. Patients were divided into groups based on whether they received balloon angioplasty alone, elective stenting, bailout stenting, or directional coronary atherectomy. In the patients undergoing balloon angioplasty, the 30-day hazard ratio for death or myocardial infarction (MI) in the group randomized to abciximab versus the placebo-treated group was 0.52 (p <0.001), for elective stenting the hazard ratio was 0.51 (p <0.001), for bailout stenting the hazard ratio was 0.38 (p <0.001), and for directional coronary atherectomy the hazard ratio was 0.38 (p = 0.007). A Cox proportional-hazards model revealed that overall, the use of abciximab decreased the composite end point of 30-day death or MI rates (hazard ratio 0.55, 95% confidence interval 0.43 to 0.69, p <0. 001). However, bailout stenting and directional coronary atherectomy were associated with increased rates of death or MI compared with balloon angioplasty, as was elective stenting in women compared with men. There was no significant increase in major bleeding episodes associated with abciximab in any of the device categories. These findings from all the controlled coronary revascularization trials using abciximab demonstrate that a decrease in death and MI is achieved with abciximab regardless of the type of device used, without an increase in significant bleeding complications.     

Results of primary percutaneous transluminal coronary angioplasty plus abciximab with or without stenting for acute myocardial infarction complicated by cardiogenic shock.

This study examines the effects of abciximab as adjunctive therapy in primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) complicated by cardiogenic shock. Abciximab improves the outcome of primary PTCA for AMI, but its efficacy in cardiogenic shock remains unknown. Case report forms were completed in-hospital and follow-up was obtained by telephone, outpatient visit, and review of hospital readmission records. A total of 113 patients with cardiogenic shock from AMI were included. All underwent emergency PTCA during which abciximab was administered to 54 patients (48%). The 2 groups of patients who received and did not receive abciximab were similar at baseline. Coronary stents were implanted slightly more often in the abciximab group (59% vs 42%; p = 0.1). A significantly improved final TIMI flow, less no-reflow, and a decrease in vessel residual diameter stenosis occurred in the abciximab group. At 30-day follow-up, the composite event rate of death, myocardial reinfarction, and target vessel revascularization was better in the abciximab group (31% vs 63%; p = 0.002). The combination of abciximab and stents was synergistic and resulted in improvement of all components of the composite end point beyond that seen with each therapy alone. Thus, abciximab therapy improves the 30-day outcome of primary PTCA in cardiogenic shock, especially when combined with coronary stenting.     

Coronary Flow Reserve During Coronary Angioplasty in Patients With a Recent Myocardial Infarction: Relation to Stenosis and Myocardial Viability

Objectives. In the present study, we examined post-stenotic coronary flow before and after percutaneous transluminal coronary angioplasty (PTCA) in patients with and without a recent myocardial infarction (MI) and related it to stenosis severity and residual viability.

Background. Post-stenotic coronary blood flow velocity reserve (CFVR) has been used with success to estimate functional stenosis severity in patients with stable angina. However, in patients with a recent MI, the impaired coronary vasodilator response of the reperfused myocardium may substantially alter the flow dynamics of the infarct-related artery.

Methods. Distal coronary flow velocities were recorded before and after PTCA in 36 patients at day 13 ± 7 (mean ± SD) after acute MI and in 38 patients without MI. The CFVR was assessed by the ratio of distal hyperemic to baseline average peak velocity, using a 0.014-in. Doppler guide wire. Stenosis severity was analyzed by quantitative coronary angiography, and infarct size was assessed scintigraphically.

Results. For similar angiographic stenosis severity, pre- and post-PTCA values of CFVR were significantly lower in patients with than without MI: 1.22 ± 0.26 versus 1.50 ± 0.45 before PTCA (p < 0.05) and 1.72 ± 0.43 versus 2.21 ± 0.74 after PTCA, respectively (p < 0.01). Although CFVR increased significantly (p < 0.0001) after angiographically successful PTCA in both study groups, abnormal CFVR (≤2.0) was still observed in 80% of patients with MI and in 44% of those without MI (MI vs. no MI, p = 0.001). Patients with an extensive infarction (relative infarct size ≥50%) and those with a small infarction (relative infarct size <50%) had comparable levels of post-PTCA CFVR (1.6 ± 0.3 vs. 1.8 ± 0.5, p = NS). Among a variety of factors, angiographic stenosis severity was the most important determinant of CFVR in both study groups.

Conclusions. In patients with a recent MI, CFVR was significantly lower than in those without MI, both before and after PTCA. Besides the presence of this postreperfusion-related impairment of the coronary vasodilating response, CFVR was mainly influenced by stenosis severity and not by residual viability.

(J Am Coll Cardiol 1996;28:1712–9)>     

Role of Coronary Artery Lumen Enlargement in Improving Coronary Blood Flow After Balloon Angioplasty and Stenting: A Combined Intravascular Ultrasound Doppler Flow and Imaging Study

Objectives. This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting.

Background. Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in ≥50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results.

Methods. To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity.

Results. The percent diameter stenosis decreased from (mean ± SD) 84 ± 13% to 37 ± 18% after angioplasty and to 8 ± 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 ± 0.79 at baseline to 1.89 ± 0.56 (p = NS) after angioplasty but increased to 2.49 ± 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 ± 2.09 vs. 5.10 ± 2.03 mm², p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001).

Conclusions. In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.

(J Am Coll Cardiol 1997;29:1520–7)     

Routine upfront abciximab versus standard periprocedural therapy in patients undergoing primary percutaneous coronary intervention for cardiogenic shock: The PRAGUE-7 Study. An open randomized multicentre study

Background: The outcome of acute myocardial infarction (AMI) complicated with cardiogenic shock is poor. The aim of this study was to analyse, whether upfront abciximab administration could improve the outcomes of cardiogenic shock. Methods: This multicentre open trial randomized 80 patients with AMI complicated by cardiogenic shock expected to undergo primary PCI into group A (routine upfront—pre-procedural—abciximab bolus followed by 12-h abciximab infusion) and group B (standard therapy). The study primary objective was 30-day combined outcome (death/reinfarction/stroke/new severe renal failure). Results: PCI was technically successful in 90% (A) versus 87.5% (B) patients. Abciximab was used in 100% (A) versus 35% (B). The primary endpoint occurred in 17 group A patients (42.5%) and 11 group B patients (27.5%, P = 0.24). Ejection fraction among survivors after 30 days was 44 ± 11% (A) versus 41 ± 12% (B, P = 0.205). Major bleeding occurred in 17.5% (A) versus 7.5% (B, P = 0.310). No differences (A versus B) were found in TIMI-flow and MBG after PCI. Conclusions: This study did not show any benefit from routine pre-procedural abciximab when compared with a selective abciximab use during the intervention in patients with cardiogenic shock undergoing primary PCI. However, small sample size of the trial preclude any definitive conclusion, a larger prospective, randomized, multicentered trial is needed.     

Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-up.

AIMS: Varying results have been reported in studies evaluating glycoprotein (GP) IIb/IIIa inhibition in primary coronary stenting of acute ST-elevation myocardial infarction (STEMI), usually with limited clinical follow-up. We performed a meta-analysis on case specific data of primary stenting in STEMI with a long-term evaluation. METHODS AND RESULTS: For this meta-analysis, studies of rescue percutaneous coronary intervention (PCI) after failed lytic therapy, plain balloon angioplasty studies and studies with an angiographic selection of patients were excluded. The ISAR-2, ADMIRAL, and ACE studies fulfilled inclusion criteria and all individual data were analysed together. The primary endpoint was the composite of death or re-infarction up to 3 years of follow-up. A total of 1101 patients, presenting for primary PCI and stenting of STEMI were randomized to abciximab (n=550) or placebo (n=551). This population had high-risk characteristics with 41% of anterior MI, 30% with a prior history of MI, 8.4% of cardiogenic shock, and 3.1% of previous coronary artery bypass graft (CABG). The primary endpoint of death or re-infarction was significantly reduced from an estimated cumulative hazard rate of 19.0% with placebo to 12.9% with abciximab [RR(95% IC): 0.633 (0.452; 0.887), P=0.008]. The mortality rate was reduced from an estimated cumulative hazard rate of 14.3% in the placebo arm to 10.9% in the abciximab arm [0.695 (0.482; 1.003), P=0.052]. Re-infarction was reduced from an estimated cumulative hazard rate of 5.5% with placebo to 2.3% with abciximab [0.41 (0.203; 0.831), P=0.013]. Major bleedings were 2.5 and 2% with and without abciximab, respectively (NS). In the control arm, both the death or MI cumulative hazard rate (54 vs. 13.5%) and mortality rate (39.7 vs. 10.1%) were four-fold higher in diabetics when compared with non-diabetics. Abciximab provided a significant benefit on the primary endpoint for diabetics [0.525 (0.303; 0.911), P=0.022]. CONCLUSION: Abciximab has a strong and persistent impact on hard clinical endpoints in patients undergoing primary stenting for STEMI.     

Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction

Objectives. The purpose of this study was to test the hypothesis that the incidence of restenosis after primary percutaneous transluminal coronary angioplasty for acute myocardial infarction is largely influenced by the preexistent coronary collateral circulation to the infarct-related coronary artery.

Background. The occurrence of restenosis after coronary angioplasty is the most limitation of this procedure. However, prediction of restenosis is difficult. Severe preexistent stenosis of the infarct-related coronary artery causing the development of collateral circulation may result in a high frequency of restenosis.

Methods. The study group consisted of 152 consecutive patients undergoing primary coronary angioplasty within 12 h after the onset of a first acute myocardial infarction. Of this group, 124 patients were angiographically followed up during the convalescent period of infarction and were classified into two groups according to the extent of preexistent collateral circulation to the infarct-related coronary artery.

Results. Restenosis occurred in 26 (38%) of 69 patients with poor or no collateral circulation (group A) in contrast to 35 (64%) of 55 patients with good angiographic collateral circulation (group B, p < 0.005). The frequency of preinfarction angina was significantly lower (p < 0.05) in group A (26% [18 of 60]) than in group B (44% [24 of 55]).

Conclusions. These findings indicate that the presence of well developed collateral circulation to the infarct-related coronary artery predicts a higher frequency of restenosis after primary coronary angioplasty. The difference in restenosis rates observed between the patients with and without good collateral circulation probably reflects the impact of underlying severity of stenosis on the long-term outcome after coronary angioplasty.     

Effect of abciximab on angiographic complications during percutaneous coronary stenting in the Evaluation of Platelet IIb/IIIa Inhibition in Stenting Trial (EPISTENT)

In the Evaluation of Platelet IIb/IIIa Inhibition in Stenting Trial (EPISTENT), abciximab reduced ischemic complications of stent implantation at 30 days and 6 months. The responsible mechanisms remain unclear. We sought to determine if abciximab decreases ischemic complications by decreasing the incidence of angiographic complications during coronary stenting. In EPISTENT, patients were randomized to stenting with abciximab (abciximab group), stenting with placebo (placebo group), or balloon angioplasty with abciximab. Angiographic complications (including major or minor dissection, distal embolization, thrombus postprocedure, side branch or other vessel occlusion, residual stenosis >50%, transient coronary occlusion, and Thrombolysis In Myocardial Infarction final flow <3) were recorded prospectively. Creatine kinase (CK)-MB enzyme levels after intervention were measured at 6-hour intervals. We analyzed angiographic complications and CK-MB elevations in the abciximab group (n = 784) and the placebo group (n = 803). Angiographic complications were 29% less frequent in the abciximab group compared with the placebo group (17.0% vs 23.8%; p = 0.001). In patients with angiographic complications, there was a nonsignificant reduction in the incidence of CK-MB elevation >3 times normal with abciximab therapy (19.7% vs 24.5% in placebo group; p = 0.314). Abciximab (compared with placebo) significantly reduced the incidence of CK-MB elevation >3 times normal in those without any angiographic complications (6.5% vs 10.7%; p = 0.007). In summary, abciximab (compared with placebo) significantly reduced angiographic complications during coronary stenting. Abciximab also prevented CK-MB elevations in patients without angiographic complications.     

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.     

Rescue use of abciximab improves regional left ventricular function after early incomplete reperfusion in acute myocardial infarction

BACKGROUND: Abciximab was shown to have important beneficial effects beyond the maintenance of epicardial coronary artery patency. However, it remains uncertain whether abciximab may lead to a better functional outcome in patients with acute myocardial infarction (AMI) and with incomplete reperfusion after primary angioplasty (PA). HYPOTHESIS: The study aimed to evaluate whether rescue use of abciximab may lead to a better functional outcome in such patients. METHODS: The study included 25 patients with first AMI who met the following criteria: (1) total occlusion of the infarct-related artery, (2) PA within 12 h of symptom onset, (3) postprocedural diameter stenosis < 30%, and final Thrombolysis in Myocardial Infarction (TIMI) flow grade 2. Echocardiographic examination was performed before and on Days 7 and 30 after PA. The study population was divided into two groups: Group 1 (usual care, n = 13) and Group 2 (rescue use of abciximab, n = 12). Baseline characteristics were similar between the two groups. RESULTS: Peak level of creatine kinase was higher in Group 1 than in Group 2 (5,800+/-2,700 vs. 3,800+/-2,000 U/I, p < 0.05). At 1 month follow-up, infarct zone wall motion score index (2.71+/-0.26 vs. 2.05+/-0.63, p < 0.01) and left ventricular (LV) volume indices were smaller in Group 2 than in Group 1, whereas LV ejection fraction was higher in Group 2 than in Group 1 (52.1+/-7.8 vs. 42.1+/-6.4, p < 0.01). At 1-month, abciximab was the only independent predictor of wall motion recovery index by multiple regression analysis. CONCLUSIONS: Rescue use of abciximab may reduce the infarct size in patients with AMI and TIMI grade 2 flow after PA, which may improve the recovery of regional LV function.     

Predictors of and outcomes of early thrombosis following balloon angioplasty versus primary stenting in acute myocardial infarction and usefulness of abciximab (the CADILLAC trial)

We sought to identify the predictors and clinical outcomes of early thrombosis after primary angioplasty and stenting for acute myocardial infarction (AMI). Little is known about the correlates and prognosis of acute and subacute thromboses after percutaneous coronary intervention (PCI) for AMI. We therefore studied the frequency, clinical determinants, and implications of early thrombosis in a large trial of patients who had primary PCI. In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications trial, 2,082 patients who had AMI were randomized in a 2 x 2 factorial design to primary stenting or to balloon angioplasty, each with and without abciximab. Early thrombosis occurred in 19 patients (0.9%) at a median of 2 days (range 0 to 23). Maximal balloon diameter was smaller, and aneurysmal and bifurcation lesions were more prevalent in the group with early thrombosis. Early thrombosis occurred in 0.4% of patients who had been randomized to receive abciximab versus 1.5% of control patients (p <0.01) and in 0.5% of patients who had been randomized to undergo stenting versus 1.4% of those who underwent balloon angioplasty (p = 0.04). By multivariate analysis, abciximab use was an independent predictor of no thrombosis (hazard ratio 0.27, 95% confidence interval 0.09 to 0.86, p = 0.026). Within 30 days, 5.3% of patients who had early thrombosis died, 32.9% developed reinfarction, and 89.5% required repeat target vessel revascularization (including bypass surgery in 11.1%). As a result, patients who had versus those who did not have early thrombosis had markedly higher rates of major adverse cardiac events at 30 days (94.7% vs 5.0%, p <0.0001) and at 1 year (94.7% vs 16.9%, p <0.0001). Patients who develop early thrombosis after primary PCI have a very high rate of major adverse cardiac events, including death and reinfarction, and usually require repeat coronary angioplasty or surgery for management. Complex baseline angiographic morphology and smaller maximal balloon diameter are predictors of early thrombosis after primary PCI for AMI. The incidence of early thrombosis after primary angioplasty and stenting is decreased by abciximab use.     

Variable response to the biological inhibition of platelets by abciximab in patients subjected to percutaneous coronary angioplasty]

INTRODUCTION AND OBJECTIVES: Abciximab has been shown to reduce the risk of thrombotic complications during coronary angioplasty, however there are still many aspects to be resolved. The aim of this study was to investigate the various biological effects of abciximab on platelets during coronary angioplasty. METHODS: The degree of platelet inhibition (with 5 and 20 mol/l concentrations of ADP), occlusion time (measurement of platelet haemostatic capacity, PFA-100), and the platelet activation markers were determined in 15 patients who underwent basal coronary angioplasty and abciximab treatment. Determinations were obtained before, 15 minutes after procedure initiation, at procedure termination, and 24 hours after procedure termination. RESULTS: More than 80% platelet aggregation inhibition was observed in 13 patients during the procedure, but after 24 hours (p < 0.05) was only detected in two. The occlusion time during the procedure was > 300 sec. in 13 patients, 6 of whom evolved to normal values after 24 hours (p < 0.05). A high correlation (p = 0.02) was found between these two parameters during the intervention, but not after 24 hours. No platelet inhibition or occlusion time changes were observed in 2 patients during the study. The expression of p-selectin increased significantly during the procedure (p < 0.05). CONCLUSIONS: The variability of platelet function inhibition and existence of circulating activation during coronary angioplasty following the administration of abciximab support the use of early analytical controls with the objective of modifying guidelines for use in order to optimize its effect or to combine it with other antithrombotic agents.     

Comparison in patients having primary coronary angioplasty of abciximab versus tirofiban on recovery of left ventricular function

In patients treated with primary coronary angioplasty, the use of abciximab improves microvascular perfusion and enhances the recovery of contractile function. This study compared the effects of the new dose regimen of tirofiban (25-microg/kg bolus followed by an 18-hour infusion at 0.15 microg/kg/min) on left ventricular function with those of abciximab in patients who underwent direct angioplasty. One hundred patients who underwent primary coronary angioplasty were randomized to receive a standard dose of abciximab or a large-dose bolus of tirofiban. The primary end point of the study was change in the infarct-zone wall motion score index between the initial and 30-day follow-up echocardiographic studies. The secondary end points were procedural evaluations before and after Thrombolysis In Myocardial Infarction (TIMI) grade flow, TIMI grade myocardial perfusion, and corrected TIMI frame count. Baseline global and regional ventricular functions were similar in the 2 treatment groups. After the procedure, a TIMI grade 3 flow was obtained in 86% of patients treated with abciximab and 88% of those receiving tirofiban (p = 1.0), whereas TIMI grade 3 myocardial perfusion was present in 70% and 76%, respectively (p = 0.65); corrected TIMI frame count was 22.5 +/- 1.9 and 22.1 +/- 2.5 (p = 0.37). After 30 days, we obtained 87 paired echocardiographic studies. The infarct-zone wall motion score index decreased from 2.20 +/- 0.3 to 1.99 +/- 0.2 in the abciximab group and from 2.18 +/- 0.3 to 1.95 +/- 0.3 in the tirofiban group (p = 0.67). Thus, in patients who had primary coronary angioplasty, abciximab, and the large-dose bolus of tirofiban showed similar effects on the initial angiographic results and 30-day recovery of left ventricular function.