Intravenous Abciximab Administration Research Articles

Intracoronary Compared With Intravenous Bolus Abciximab Application During Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction

The aim of the AIDA STEMI (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction. The AIDA STEMI trial randomized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group. CMR can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights. We enrolled 795 patients in the AIDA STEMI CMR substudy. CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory-masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed. The area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the intracoronary and the intravenous abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intramyocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction. This largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events.

Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: A meta-analysis of clinical trials

Successful reperfusion of epicardial coronary arteries does not necessarily result in actual myocardial perfusion. Local intracoronary (IC) delivery of GP IIb/IIIa inhibitors (GPI) has been proposed to achieve further clinical efficacy when compared to standard intravenous (IV) administration. However clinical trials have shown conflicting results. The aim of the present study was to compare IC with IV abciximab administration on mortality and MACEs in patients with ACS undergoing PCI. We performed a meta-analysis of all available clinical trials comparing intracoronary versus intravenous abciximab administration. At short-term analysis, incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.56; 95% CI 0.35-0.89; p=0.015). Interestingly, subgroup analysis showed that most benefit was coming from those studies with a main baseline LVEF<50% (OR=0.33 95% CI 0.18-0.59). Similarly, long-term incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.47; 95% CI 0.31-0.71; p<0.001), with most benefit coming from those studies enrolling patients with a main baseline EF<50% (OR=0.38 95% CI 0.23-0.63 p<0.001). In addition, long-term incidence of death was also lower in the IC group than in the IV group (OR=0.42; 95% CI 0.20-0.86; p=0.009). Our meta-analysis provides evidence of a net clinical benefit for intracoronary versus intravenous abciximab administration, with the highest benefit observed in high-risk ACS patients, such as those with reduced baseline LVEF.

Updated evidence on intracoronary abciximab in ST-elevation myocardial infarction: A systematic review and meta-analysis of randomized clinical trials

Intracoronary (IC) abciximab administration remains a promising approach aimed to increase a drug concentration in the target area and possibly improve clinical outcomes in the setting of ST-segment elevation myocardial infarction (STEMI). The goal of this literature review and meta-analysis is to update available knowledge comparing IC and intravenous (IV) abciximab administration in STEMI patients. A total of 7 randomized clinical trials (RCTs) with a median follow-up of 3 months were included in the meta-analysis (n = 3311). All-cause mortality was selected as the primary end point while recurrent myocardial infarction (re-MI), target vessel revascularization (TVR) and major bleeding complications were the secondary end points. IC abciximab did not provide any benefits in terms of all-cause mortality as compared with IV abciximab (odds ratio [OR] 0.67; 95% confidence interval [CI] 0.34-1.34). However, this neutral effect was driven by the AIDA STEMI trial. The IC route was associated with a reduced rate of re-MI when compared with IV administration (OR 0.61; 95% CI 0.40-0.92) but the difference disappeared after one of the RCTs was excluded from the analysis. Both strategies were equal regarding TVR (OR 0.66; 95% CI 0.40-1.09) and major bleeding complications (OR 1.18; 95% CI 0.76-1.83). Our updated meta-analysis shows that the clinical superiority of IC over IV abciximab administration in STEMI patients is no longer clear after the release of the AIDA STEMI trial results. Further research in high-risk STEMI patients is warranted to finally determine clinical advantages of IC vs IV abciximab administration.

Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris during percutaneous coronary interventions under an adjunctive antithrombotic therapy with abciximab: design and rationale of the High Intensity Transient Signals ReoPro (HITS-RP) study

BackgroundEmbolization of atherosclerotic debris from the rupture of a vulnerable atherosclerotic plaque occurs iatrogenically during percutaneous coronary interventions (PCI) and can induce myocardial necrosis. These microembolizations are detected as high intensity transient signals (HITS) using intracoronary Doppler technology.Presentation of the hypothesisIn the presented study we will test if abciximab (ReoPro®) infusion reduces high intensity transient signals in patients with stable angina pectoris undergoing PCI in comparison to standard therapy alone.Testing the hypothesisThe High Intensity Transient Signals ReoPro® (HITS-RP) study will enroll 60 patients. It is a prospective, single center, randomized, double-blinded, controlled trial. The study is designed to compare the efficacy of intravenous abciximab administration for reduction of microembolization during elective PCI. Patients will be randomized in a 1:1 fashion to abciximab or placebo infusion. The primary end point of the HITS-RP-Study is the number of HITS during PCI measured by intracoronary Doppler wire. Secondary endpoints are bleeding complications, elevation of cardiac biomarkers or ECG changes after percutaneous coronary interventions, changes in coronary flow velocity reserve, hs-CRP elevation, any major adverse cardio-vascular event during one month follow-up.Implications of the hypothesisThe HITS-RP-Study addresses important questions regarding the efficacy of intravenous abciximab administration in reducing microembolization and periprocedural complications in stable angina pectoris patients undergoing PCI.Trial registrationThe trial is registered under http://www.drks-neu.uniklinik-freiburg.de/drks_web/:DRKS00000603.

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.

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.

Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration

Background— Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. Methods and Results— A total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P =0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P =0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group ( P =0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P =0.786). Conclusions— In ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00927615.

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.

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 …

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

Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention—Effects on soluble CD40 ligand concentrations

Introduction CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI. Methods Patients were randomized to receive IC ( n = 25) or IV ( n = 25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60 min post bolus administration. Results Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6 ± 42.13 pg/mL vs 124.9 ± 43.04 pg/mL, P = 0.49). At 60 min post PCI, however, sCD40L levels decreased by 23% ( P < 0.001) in the IC group and by 11% ( P < 0.001) in the IV group. sCD40L levels 60 min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04 ± 12.21 pg/mL vs 99.92 ± 25.89 pg/mL, P < 0.001). Conclusion In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation.

Prehospital versus periprocedural abciximab in ST -elevation myocardial infarction treated by percutaneous coronary intervention

To investigate the potential benefit of an earliest possible out-of-hospital start of abciximab (ReoPro) therapy in ST-elevation myocardial infarction (STEMI; Lilly, Bad Homburg, Germany) and planned primary percutaneous intervention compared with periprocedural abciximab treatment on reperfusion and clinical outcome. Randomization of one hundred and one patients with STEMI to prehospital or periprocedural abciximab treatment. Evaluation of thrombolysis in myocardial infarction (TIMI) flow, ST-segment resolution, myocardial blush grade, and maximal creatine kinase release before and after as well as clinical follow-up until 6 months after the index event. Prehospital abciximab (group 1) was initiated a median of 101 min (37-165 min) earlier compared with periprocedural treatment (group 2). Initial TIMI 3 flow (24 vs. 15%, P=NS), ST-segment resolution before percutaneous coronary intervention (PCI) (<30%: 33 vs. 46%, P=NS; >70%: 38 vs. 33%, P=NS), post-PCI myocardial blush grade 2 and 3 (72 vs. 75%, P=NS), maximal cardiac enzyme release (creatinine kinase MB median 77 U/l; range 33-137 vs. 74 U/l; range 39-143 U/l, P=NS), and 6 months follow-up (recurrent myocardial infarction or repeat coronary intervention, and PCI, need for coronary bypass surgery) did not differ significantly between both treatment groups. Prehospital intravenous administration of abciximab, although safe and feasible in a trained surrounding, does not add angiographic or clinical benefit to patients with STEMI.

Effects of intracoronary compared to intravenous abciximab administration in patients undergoing transradial percutaneous coronary intervention: A sub-analysis of the EASY trial

Background In the EASY trial, we have shown the clinical equivalence between abciximab bolus-only and abciximab bolus followed by 12-h infusion in a wide spectrum of patients after percutaneous coronary intervention (PCI). Some reports have suggested better outcomes following intracoronary (IC) abciximab administration compared to intravenous (IV) delivery. We sought to compare cardiac biomarkers release and early and late clinical outcomes after IC or IV abciximab bolus delivery. Methods From 1005 patients randomized in the EASY trial and undergoing transradial coronary stent implantation, 208 received IC abciximab bolus and 797 received IV abciximab bolus. Route of administration was left to operators' discretion. Creatine Kinase-MB, and Troponin-T (Tn-T) were obtained immediately prior to angiography, 4–6 h after PCI and the next day. MACE (death, MI, TVR) rate was evaluated at 30 days, 6 months and 12 months. Results There were more patients with acute coronary syndrome (75% vs 64%, P = 0.004) and previous MI (53% vs 42%, P = 0.005) in the IC group and more patients with ≥ 3 dilated sites in the IV group (2% IC vs 7% IV, P = 0.03). After PCI, the extent of Tn-T and CK-MB release remained comparable in both groups. The MACE rate was 2% in both groups at 30 days, 9% in IC bolus vs 5% in IV bolus ( P = 0.04) at 6 months and 10% in IC bolus vs 9% in IV bolus ( P = 0.50) at 12 months. By multivariate analysis, IC abciximab bolus was not associated with better outcomes at 12 months compared to IV bolus (HR 1.07, 95% CI 0.82–1.35, P = 0.62). Conclusion Compared to IV abciximab administration, IC abciximab was not associated with less cardiac biomarkers release or better clinical outcomes after uncomplicated transradial PCI. Further studies are required in clinical scenarios including patients with higher thrombotic burden and/or occluded vessels as in primary and rescue PCI.

Emergency Administration of Abciximab for Treatment of Patients With Acute Ischemic Stroke: Results of an International Phase III Trial

A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset. An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke. The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221; P=0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, approximately 5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (P=0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo). This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.

Acute Left Main Occlusion During Percutaneous Coronary Intervention Associated with Heparin Induced Thrombocytopenia with Thrombosis Syndrome

A 76-year-old male was admitted with Braunwald IIIB unstable angina and treated with intravenous heparin. Coronary angiography 20 days later revealed a severe stenosis in the left circumflex artery. During coronary angioplasty thrombus developed in the circumflex artery, extended in the left main and lead to its occlusion. Normal left coronary artery patency and flow were achieved after intracoronary and intravenous administration of abciximab, and multiple stenting. Platelet-count decrease and an ELISA assay documented the presence of heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). HITTS should be suspected after acute thrombus formation during coronary angioplasty.

Initial Experience with the Combination of Reteplase and Abciximab for Thrombolytic Therapy in Peripheral Arterial Occlusive Disease: A Pilot Study

To report the efficacy of catheter-directed thrombolysis with a combination of a thrombolytic agent (reteplase) and a glycoprotein (GP) IIb/IIIa platelet receptor antagonist (abciximab) in peripheral arterial occlusive disease. Fifteen patients with lower extremity arterial thromboses (age range, 40-96 y; mean, 73 y) were prospectively enrolled in a protocol approved by the Institutional Review Committee. Nine patients had native arterial occlusions, three (33%) of whom had subacute symptoms (>14 d) and one of whom had chronic symptoms (>3 mo). Four patients had acute arterial graft thromboses. Two patients with lower extremity bypass grafts presented with subacute limb ischemia. All patients received catheter-directed infusion of reteplase (0.5 U/h) in combination with intravenous administration of abciximab (0.25-mg/kg bolus followed by 0.125 microg/kg/min infusion) for 12 hours without systemic heparinization. The thrombolytic success was studied by Doppler ultrasonography (US) and angiography. Complete thrombolysis and clinical success was achieved in 14 of the 15 patients (93%). One patient with unsuccessful thrombolysis underwent major amputation. The mean thrombolysis time per Doppler US procedure was 6.8 hours (range, 2-30 h). Angiographic patency was achieved at a mean of 17.5 hours (range, 4-36 h) corresponding to a mean dose of reteplase of 8.8 U. The mean increase in ankle-brachial index was 0.52 (range, 0-0.9). No major hemorrhagic complications occurred. The 30-day primary patency rate was 93%. The combination of reteplase and abciximab in catheter-directed arterial thrombolysis is feasible and effective. This combination therapy pilot study suggests short thrombolysis times and minimal adverse effects in catheter-directed thrombolytic therapy for peripheral arterial occlusive disease.