Abciximab-treated Patients Research Articles

Optimizing Platelet P2Y12 Inhibition for Patients Undergoing PCI

Guidelines recommend that dual antiplatelet therapy using aspirin and clopidogrel should be administered to the majority of patients with acute coronary syndromes, including those undergoing percutaneous coronary intervention (PCI). However, the results of a large randomized, placebo-controlled study suggest that a 300-mg loading dose of clopidogrel must be administered at least 15 h prior to PCI in order to achieve a significant reduction in peri-PCI thrombotic events. Other data suggest that 2 h of pretreatment may be sufficient if a 600-mg loading dose is used. Since it is often difficult to achieve an adequate pretreatment goal with clopidogrel in clinical practice, more rapid achievement of platelet P2Y(12) inhibition may improve patient outcomes. Prasugrel, [6-[2-(3,4-diflurophenyl) cyclopropyl1-1-y1] amino-2-propylthio-9-D-ribofuranosyl-9H-purine (AZD6140), and cangrelor are platelet P2Y(12) receptor antagonists currently in development that offer faster acting inhibition of adenosine diphosphate (ADP)--induced platelet aggregation. These agents act upon the same platelet receptor as clopidogrel, but are distinguished by their routes of administration, reversibility, and pharmacodynamic properties. Prasugrel is an orally administered agent that provides faster, higher, and more consistent inhibition of platelet aggregation than clopidogrel. The results of Phase II testing suggest that the risk of bleeding is similar in prasugrel- and clopidogrel-treated patients. AZD6140 is another orally administered platelet inhibitor with rapid and reversible action. Again, Phase II testing suggests similar bleeding risk for clopidogrel. Preliminary evidence suggests that clinical outcomes may be better in prasugrel- and AZD6140-treated patients than in clopidogrel-treated patients. Cangrelor is an intravenously administered, reversible, short-acting agent with a rapid onset of activity. Bleeding risk and clinical outcomes data are similar in cangrelor- and abciximab-treated patients. The results of ongoing Phase III clinical trials involving more than 40,000 patients will demonstrate whether these agents fulfill their potential to improve outcomes in PCI-treated patients by providing faster, higher, and more consistent inhibition of platelet aggregation.

Alveolar Hemorrhage: An Underdiagnosed Complication of Treatment with Glycoprotein IIb/IIIa Inhibitors

Alveolar hemorrhage (AH) is a rare complication of treatment with GP IIb/IIIa inhibitors. Hemoptysis, a constant sign, lacks in specificity, and may occur in confounding syndromes such as pulmonary edema, pulmonary infarction, and pneumonia. Nonspecific symptoms and signs often delay the diagnosis, thereby allowing serious or even fatal disease progression. Here, we performed a large-scale retrospective analysis to define the incidence and risk factors of AH in the setting of GP IIb/IIIa inhibitors therapy. Randomized controlled trials demonstrate that treatment with glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors may improve the outcome of acute myocardial infarction (AMI) and angioplastic procedures. However, this treatment may rarely lead to severe hemorrhagic complications, in particular AH. Unfortunately, the incidence and risk factors of AH remain poorly defined. We reviewed for the period extending from August 1998 to January 2005 consecutive histories of AMI patients receiving coronary arteriography and treatment with either eptifibatide or abciximab. Concomitantly admitted AMI patients not treated with GP IIb/IIIa inhibitors were reviewed and served as a control group. The diagnosis of AH required the demonstration of typical symptoms and signs including dyspnea, hemoptysis, arterial hypoxemia, pulmonary radiographic changes, and, when available, bronchoscopic signs for AH. Potential covariates including pulmonary disease, pulmonary hypertension, smoking, and use of other anticoagulant or antiplatelet agents were evaluated. Six of 1,810 patients (0.33%) receiving eptifibatide and five of 3,648 patients (0.14%) receiving abciximab exhibited typical symptoms and signs of AH. Contrarily, only one of 4,136 patients (0.025%) receiving no GP IIb/IIIa inhibitors presented with similar symptoms and signs. There was no fatal outcome, though two patients required blood transfusions. Statistically significant differences were found between control patients and patients receiving eptifibatide alone (P = 0.004). There was also a significant difference between untreated patients and those receiving eptifibatide and abciximab (P = 0.017). No differences were found between eptifibatide and abciximab-treated patients (P = 0.19) or between abciximab and untreated control patients (P = 0.105). AH is a rare complication of treatment with GP IIb/IIIa inhibitors. Its incidence ranged from 0.14% in patients treated with abciximab to 0.33% in those receiving eptifibatide. Compared to a control group, patients treated with GP IIb/IIIa inhibitors had a statistically increased risk for AH.

Variability in Extent of Platelet Function Inhibition After Administration of Optimal Dose of Glycoprotein IIb/IIIa Receptor Blockers in Patients Undergoing a High-Risk Percutaneous Coronary Intervention

The Ultegra Rapid Platelet Function Assay was used to measure the inhibition of platelet aggregation at baseline and 10 minutes and 8 hours after starting therapy in 114 patients undergoing high-risk percutaneous coronary intervention with the planned use of a glycoprotein IIb/IIIa inhibitor. The abciximab-treated patients received a 0.25 mg/kg bolus, followed by a 0.125 microg/kg/min infusion for 12 hours; the eptifibatide-treated patients received 2 boluses of 180 microg/kg administered 10 minutes apart, followed by a 2 microg/kg/min infusion for 24 hours; the tirofiban-treated patients received a 25 microg/kg bolus, followed by a 0.15 microg/kg/min infusion for 18 hours. Ten minutes after starting therapy, the mean level of platelet inhibition was 86 +/- 9% for abciximab, 92 +/- 6% for eptifibatide, and 95 +/- 5% for tirofiban (p <0.001); > or =95% platelet inhibition was achieved in 29% of the patients treated with abciximab, 44% of those receiving eptifibatide, and 68% of the those receiving tirofiban (p = 0.02). In conclusion, at the evaluated doses, tirofiban seemed to be the most effective drug in achieving "optimal" platelet inhibition very early after percutaneous coronary intervention.

Three-year duration of benefit from abciximab in patients receiving stents for acute myocardial infarction in the randomized double-blind ADMIRAL study

The Abciximab Before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-term Follow-up (ADMIRAL) study demonstrated that early inhibition of the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor with abciximab led to improved coronary patency, left ventricular function, and clinical outcomes. The current long-term follow-up study evaluated the durability of the positive outcomes. The randomized double-blind ADMIRAL trial enrolled 300 patients who received either abciximab plus stenting or placebo plus stenting for the treatment of ST-elevation myocardial infarction (STEMI). Abciximab (bolus of 0.25 mg/kg body weight, followed by 12 h infusion of 0.125 microg/kg per min) was administered to 149 patients, whereas 151 patients received placebo. Long-term follow-up was conducted in a blinded manner by either patient chart review or telephone interview. Long-term follow-up data were obtained on 288 patients (96%). After 3 years, using an intent-to-treat analysis, the outcome of all-cause mortality occurred in 9.1% of abciximab-treated patients when compared with 12.2% of placebo patients, absolute and relative risk reductions of 3.1 and 25%, respectively (P=0.36). Parallel Kaplan-Meier curves were observed for the cumulative incidence of death or re-infarction, which was reduced from 16.9% in the placebo group to 11.8% in the abciximab group, absolute and relative risk reductions of 5.1 and 30%, respectively (P=0.20). Rates of recurrent ischaemia were significantly reduced from 21.7 to 11.5% (P=0.05). Adjunctive abciximab to primary stenting for STEMI elicits favourable clinical outcomes with the same absolute risk reductions of hard clinical outcomes from 30 days up to 3 years of follow-up.

Circulating procoagulant microparticles and soluble GPV in myocardial infarction treated by primary percutaneous transluminal coronary angioplasty. A possible role for GPIIb‐IIIa antagonists

Circulating procoagulant microparticles (MP) were measured as markers of vascular damage and prothrombotic risk in patients undergoing ST-segment myocardial infarction (STEMI) treated by primary percutaneous transluminal coronary angioplasty (PTCA) and additional GPIIb-IIIa antagonists. Cells possibly more responsive to GPIIb-IIIa (alpha(IIb)beta(3)) antagonists were evidenced through MP phenotypes by comparison with healthy volunteers (HV) and STEMI patients treated by PTCA without GPIIb-IIIa antagonist (CP). In 50 STEMI patients, blood samples were collected at day 1 and day 6. Circulating procoagulant MP were captured on annexin V and quantified by prothrombinase assay as nanomolar phosphatidylserine equivalents (nm PhtdSer). Platelet activation by thrombin was confirmed through independent measurement of soluble GPV (sGPV). With respect to HV, procoagulant MP levels were high in patients with STEMI or unstable angina, platelet-derived MP and elevated sGPV testifying to significant platelet activation. A substantial release of endothelial-derived MP was evidenced simultaneously. In abciximab-treated patients, procoagulant MP, mainly of platelet origin, decreased precociously at day 1 (4.2 +/- 0.6 vs. CP 15.5 +/- 2.1 nm PhtdSer; P = 0.001) together with sGPV (36 +/- 3 vs. CP 58 +/- 8 ng mL(-1); P = 0.02). Leukocyte-derived MP decreased at day 6 (0.12 +/- 0.04 vs. CP 0.56 +/- 0.12 nm PhtdSer; P = 0.01) suggesting a possible effect on underlying inflammatory status. In patients presenting cardiovascular events at 6-month follow-up, procoagulant MP levels at day 1 could be indicative of a worsened outcome. MP could constitute a relevant parameter for the follow-up of STEMI patients treated by GPIIb-IIIa antagonists.

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 × 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 vs $13,000 ± $6,006, 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.

Carotid Angioplasty and Stent Placement: A Prospective Analysis of Perioperative Complications and Impact of Intravenously Administered Abciximab

To determine the frequency of perioperative complications since the introduction of abciximab, we prospectively evaluated our experience in a consecutive series of patients undergoing carotid angioplasty and stent placement (CAS). CAS has been introduced recently for treatment of carotid artery stenosis. A major limitation to this modality is the risk of perioperative thromboembolic and ischemic events. To reduce the risk of ischemic complications, abciximab, a platelet glycoprotein IIb/IIIa receptor inhibitor, has been introduced as adjunctive treatment for high-risk patients. Each patient was evaluated by a neurologist before, immediately after, and 24 hours after CAS for identification and classification of new neurological deficits. Bleeding events or other complications during hospitalization were recorded. Bleeding complications were classified as major (hemoglobin decrease,g5 g/dl), minor (hemoglobin decrease, 3-5 g/dl), or insignificant. Abciximab was administered intravenously as a single bolus (0.25 mg/kg) and then via infusion (10 microg/min) for 12 hours as an adjunct to CAS in patients considered to be at high risk for thromboembolic events owing to recent ischemic symptoms and/or complex lesion morphology. Intravenously administered abciximab was used in 37 patients (mean age, 70 yr; 21 patients were men) as an adjunct to high-risk CAS. Thirty-three other patients underwent CAS performed with standard intraprocedural heparinization (mean age, 69 yr; 17 patients were men). Minor ischemic strokes were observed in 1 of 37 abciximab-treated patients and in 4 of 33 heparin-treated patients. No major ischemic strokes were observed in either group. Transient neurological deficits were observed in nine patients in the abciximab-treated group and in one patient in the heparin-treated group. Transient neurological deficits in abciximab-treated patients were mainly related to hemodynamic factors (associated with balloon inflation in two patients and with hypotension in another two patients) or occurred after completion of infusion (in three patients). Minor bleeding complications were observed in three patients who received abciximab and in four patients who received standard heparinization. Major bleeding complications were observed in four patients from each group. Two patients who received abciximab developed intracerebral hemorrhages; one hemorrhage was fatal. The frequency of ischemic stroke in high-risk patients (3%) with the use of intravenously administered abciximab was lower, but not significantly so, than rates observed in lower-risk patients (12%), although the benefit was lost because of the high rate of intracranial hemorrhages (5%). Further efforts are required to determine appropriate selection criteria for use of intravenously administered abciximab and the effect of other strategies that involve distal protection devices.

Meta-analysis of effectiveness and safety of abciximab versus eptifibatide or tirofiban in percutaneous coronary intervention

Three platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been evaluated in patients undergoing percutaneous coronary intervention (PCI). One of these agents, abciximab, is structurally and pharmacologically quite different from the other 2, eptifibatide and tirofiban. We conducted a meta-analysis to determine whether different antagonist types achieved different clinical outcomes, possibly related to their structural differences. Odds ratios (OR) were calculated and a random effects model was used to combine the outcomes of 14,644 patients enrolled in 8 prospective, randomized, placebo-controlled clinical trials assessing treatment with a GP IIb/IIIa inhibitor to prevent ischemic complications of PCI. Neither abciximab (OR 0.69; 95% confidence interval [CI] 0.4 to 1.9) nor eptifibatide or tirofiban treatment (OR 0.74; 95% CI 0.4 to 1.28) resulted in reductions in mortality. Only the abciximab-treated patients had reductions in myocardial infarction (4.3% vs 8.5%, OR 0.49; 95% CI 0.40 to 0.59). There was no effect of eptifibatide or tirofiban on myocardial infarction (OR 0.85; 95% CI 0.69 to 1.04). Urgent revascularization was reduced in both abciximab-treated (2.7% vs 6.2%, OR 0.42; 95% CI 0.34 to 0.53) and eptifibatide- and tirofiban-treated (4.2% vs 5.5%, OR 0.76; 95% CI 0.60 to 0.96) groups. Only abciximab-treated patients had increased major bleeding (5.8% vs 3.8%; OR 1.53; 95% CI 1.24 to 1.90). There was no effect of eptifibatide or tirofiban on major bleeding (5.0% vs 4.3%; OR 1.19; 95% CI 0.94 to 1.52). Thus, significant differences exist between clinical outcomes achieved by abciximab and those achieved by eptifibatide or tirofiban following PCI procedures.

Current status of cardiac surgery in the abciximab-treated patient

Background. Early surgical experience with abciximab and other glycoprotein (GP) IIb/IIIa receptor antagonists suggested a tendency toward excessive bleeding in patients treated with these agents. With increased use of GP IIb/IIIa inhibitors, cardiac surgeons have become aware of their hazards, as well as potential benefits, during and after cardiac surgery. Although published experience with the GP IIb/IIIa inhibitor abciximab is limited in scope, it suggests management guidelines for urgent coronary artery bypass grafting in abciximab-treated patients. As more urgent and elective surgical data are presented, a clearer picture of true bleeding risk will evolve. Methods. Two large retrospective studies examining reexploration for postoperative bleeding have identified risk factors, including advanced age, preoperative renal dysfunction, and operation/reoperation other than coronary artery bypass grafting. Other risk factors for transfusion requirement and increased morbidity and mortality are emergent operation, postoperative coagulopathy, and prolonged bypass time. Results. To minimize real and perceived bleeding effects, some authors have suggested delaying operation until platelet function has normalized, employing platelet transfusion in patients in whom delay is not possible, and exacting heparin management during cardiopulmonary bypass. Later reports have not noted increased bleeding when incorporating these modifications plus early platelet transfusion, if required. Further experience with abciximab removal and reversal may also ultimately reduce or eliminate excess transfusion requirements. Conclusions. Surgeons should work closely with perfusionists and anesthesiologists on issues of heparinization in the abciximab-treated patient. The apparent paradox of preserved platelet numbers and depressed platelet function with abciximab use has led to speculation about a role for this agent and other shorter-acting GP IIb/IIIa inhibitors for “platelet anesthesia” during cardiopulmonary bypass. With careful surgical care, GP IIb/IIIa receptor antagonists can maintain and improve beneficial outcomes.

Clinical experience in coronary bypass surgery for abciximab-treated patients

Abciximab effectively inhibits platelet aggregation and, therefore, there is considerable concern regarding bleeding complications in patients who require coronary artery bypass graft (CABG) surgery while affected by the drug. This presentation reviews the available published literature regarding CABG in abciximab-treated patients, the clinical results of emergency CABG in 12 patients, and management suggestions for the abciximab-treated patient requiring emergency surgery.

Platelet inhibitors and bleeding in cardiac surgical patients

A variety of measures may affect bleeding and transfusion requirements in abciximab-treated patients. These measures include recognition of the risk factors for increased bleeding and transfusion requirements, use of proper transfusion practices, conservation or increasing of red cell mass, appropriate heparin dosing and protamine reversal, reversal of anticoagulation, awareness of factors that affect activated clotting time (ACT), and appropriate anticoagulation for cardiopulmonary bypass.

Coronary artery bypass graft in abciximab-treated patients

In an assessment of available literature regarding appropriate treatment algorithms for patients who fail cardiac interventions and require coronary bypass grafting with abciximab “on board,” few surgeons reported significant variation in bleeding or other issues. There are many problems with postmarketing data collection, and such data would lack rigor and randomization. Prospective collection of data would be extremely difficult. Few patients go to surgery nowadays, and it is generally believed that because of the wealth of data supporting glycoprotein (GP) IIb/IIIa inhibition associated with percutaneous intervention, it would be unethical to subject patients to a placebo control in the catheterization laboratory. For those reasons, we returned to the clinical trials database and did a retrospective analysis of EPILOG and EPISTENT, the two studies that most appropriately reflect state-of-the-art intervention and abciximab use. We omitted EPIC, the original registration trial of high-risk angioplasty patients, because this study no longer reflects current recommendations regarding heparinization, abciximab administration, or groin care.

Occurrence and clinical significance of pseudothrombocytopenia during abciximab therapy

OBJECTIVESThis study determined the incidence of pseudothrombocytopenia during abciximab therapy administered for percutaneous coronary interventions and compared the clinical course of patients with pseudothrombocytopenia with the clinical courses of patients with thrombocytopenia and patients with normal platelet counts.BACKGROUNDAlthough pseudothrombocytopenia has been previously reported during therapy with abciximab, the incidence and significance of this occurrence are unknown. The failure to differentiate pseudothrombocytopenia from thrombocytopenia could lead to unnecessary interruption of abciximab infusions or to platelet transfusions.METHODSThe incidences of pseudothrombocytopenia and thrombocytopenia were determined in four large placebo-controlled abciximab trials: c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE), Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation of Percutaneous Transluminal Coronary Angioplasty to Improve Long-term Outcome of c7E3 GpIIb/IIIa Receptor Blockade (EPILOG) and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT). The clinical features, bleeding complications and major clinical outcomes of patients with pseudothrombocytopenia and those with thrombocytopenia were compared with each other and with those of patients with normal platelet count.RESULTSPseudothrombocytopenia occurred in 2.1% (95% confidence intervals [CI]: 1.7%, 2.5%) of abciximab-treated patients and in 0.6% of placebo-treated patients (p < 0.001). Thrombocytopenia occurred in 3.7% (95% CI: 3.2%, 4.2%) of abciximab-treated patients and in 1.8% (95% CI: 1.3%, 2.3%) of placebo-treated patients (p < 0.001). Patients with thrombocytopenia had significantly higher rates of major bleeding, major decreases in hemoglobin and increased transfusion requirements of both blood and platelets compared with those without thrombocytopenia. By contrast, pseudothrombocytopenic patients did not differ from patients with normal platelet counts in any of the measures of blood loss or transfusion requirements. Thrombocytopenic patients, but not those with pseudothrombocytopenia, had increased rates of revascularization at 30 days and six months. As previously reported, there was also a higher rate of death and myocardial infarction in the thrombocytopenic patients.CONCLUSIONSPseudothrombocytopenia is the cause of more than one third (36.3%) of low platelet counts in patients undergoing coronary interventions who are treated with abciximab. This study demonstrates that pseudothrombocytopenia is a benign laboratory condition that does not increase bleeding, stroke, transfusion requirements or the need for repeat revascularization. It is important to recognize pseudothrombocytopenia so that the beneficial effects of abciximab are not lost by premature termination of therapy.

Emergency coronary artery bypass graft surgery in abciximab-treated patients

Background. Although the platelet antiaggregant abciximab is frequently used with percutaneous coronary interventions, results of emergency coronary artery bypass graft operations in patients recently treated with abciximab are poorly characterized.Methods. During a 29-month period, 12 patients required emergency coronary artery bypass grafting within 12 hours (mean, 1.9 hours) of abciximab therapy. Our full standard heparin dose regimen was used (mean heparin dose, 53,000 U per patient). Each patient received a single platelet transfusion dose after protamine administration, and further blood products were transfused as necessary. Clinical outcome and transfusion requirements were compared with predicted results based on risk-adjusted historical patients.Results. No patients died and none were returned to the operating room for coagulopathy-related bleeding. Per-patient transfusion requirements were as follows: red blood cells, 3.6 units; apheresis platelets, 1.4 units; and fresh frozen plasma, 1.5 units. As compared with predicted values, there was no excessive incidence of mortality, stroke, or red blood cell transfusion requirements.Conclusions. Emergency coronary artery bypass graft operations using full-dose heparin can be performed successfully in acutely ischemic abciximab-treated patients. Prophylactic transfusion of platelets after protamine administration appears to be useful.

Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis ( reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial)

We evaluated the effects of abciximab treatment during early angioplasty after clinically failed thrombolysis for acute myocardial infarction. In the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial of reteplase versus alteplase for acute infarction (n = 15,059), 392 patients underwent angioplasty a median of 3.5 hours after thrombolysis and had complete procedural data. We compared 30-day mortality and in-hospital outcomes between patients who received abciximab (n = 83) and those who did not (n = 309), and (among patients given abciximab) between those randomized to alteplase versus reteplase. Patients given abciximab had anterior infarction less often, but were more often in Killip classes III or IV. The 30-day mortality rate tended to be lower with abciximab (3.6% vs 9.7%, p = 0.076), more so after adjustment for baseline differences (p = 0.042). The composite of death, stroke, or reinfarction did not differ significantly with abciximab treatment (12% vs 14%, p = 0.7), but it occurred less often among abciximab-treated patients who had been randomized to reteplase (n = 55) versus alteplase (n = 28) (7% vs 21%, p = 0.08). Severe bleeding was increased among abciximab-treated patients (3.6% vs 1.0%, p = 0.08), despite less heparin use. No intracranial hemorrhages occurred with abciximab. The use of abciximab for early angioplasty after clinically failed thrombolysis resulted in trends toward lower 30-day mortality and increased bleeding.

Platelet glycoprotein IIb/IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional coronary atherectomy

We determined the efficacy of abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, combined with low-dose weight-adjusted heparin in reducing ischemic complications in patients undergoing directional coronary atherectomy (DCA). The Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial demonstrated a reduction in the incidence of non–Q-wave myocardial infarction in DCA patients who were treated with abciximab bolus and infusion plus heparin. This benefit, however, was associated with increased bleeding complications. Of the 2,792 patients who had coronary intervention in the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa receptor blockade (EPILOG) trial, 144 (5%) underwent DCA. Patients were randomly assigned to 3 treatment groups: placebo with standard-dose, weight-adjusted heparin; abciximab with low-dose weight-adjusted heparin; or abciximab with standard-dose weight-adjusted heparin. Study end points included 30-day and 6-month composite incidence of death, myocardial infarction, or revascularization. Compared with those undergoing percutaneous transluminal coronary angioplasty (PTCA), DCA patients had a higher rate of myocardial infarction (11.1 % vs 4.9%, p = 0.001) and predominantly non–Q-wave myocardial infarction (9.7% vs 4.4%, p = 0.004). Abciximab was associated with a 57% lower combined rate of death, myocardial infarction, or urgent revascularization within 30 days following DCA (20% placebo vs 8.7% abciximab with low-dose heparin) without excess risk of bleeding complications. A combined analysis of data from the EPIC and EPILOG trials demonstrates a reduction in the rate of death or myocardial infarction (19.9% vs 8.4%, p = 0.008) at 30 days that was sustained for up to 6 months in the abciximab-treated patients. These findings support the premise that non–Q-wave myocardial infarction in DCA patients are platelet mediated.

Partial Reversal of Heparin Anticoagulation by Intravenous Protamine in Abciximab-Treated Patients Undergoing Percutaneous Intervention

Serious hemorrhage and vascular complications after abciximab therapy are associated with elevated activated clotting time values. Our preliminary experience suggests that low-dose intravenous protamine administration is both safe and effective in reducing elevated in-laboratory activated clotting time values and the potential for serious hemorrhage in abciximab-treated patients.