Tirofiban-induced thrombocytopenia.

Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Although generally considered safe, tirofiban has been reported to be associated with thrombocytopenia in several case reports and clinical trials. The pathogenesis for this adverse reaction is not entirely understood, is thought to be due to immune-mediated reaction. This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.

Tirofiban-induced thrombocytopenia usually occurred within the first 24 h of treatment, frequently accompanied by bleeding symptoms. The majority of the time, supportive care is used to manage this adverse event, and the platelet count often returns to normal in a few days.Although the exact cause of this adverse response is unknown, it is thought to be due to drug-dependent antibodies that bind to GP IIb/IIIa, presumably after tirofiban-induced conformational change.Age ≥ 65 years, white blood cell ≥ 12 × 10⁹/L, diabetes mellitus, congestive heart failure, and chronic kidney disease were identified as the risk factors for tirofiban-induced thrombocytopenia. Further investigations are needed for this.

Fatty acid oxidation fuels agonist-induced platelet activation and thrombus formation: Targeting ß-oxidation of fatty acids as an effective anti-platelet strategy.

Platelet mitochondria possess remarkable plasticity for oxidation of energy substrates, where metabolic dependency on glucose or fatty acids is higher than glutamine. Since platelets metabolize nearly the entire pool of glucose to lactate rather than fluxing through mitochondrial tricarboxylic acid cycle, we posit that majority of mitochondrial ATP, which is essential for platelet granule secretion and thrombus formation, is sourced from oxidation of fatty acids. We performed a comprehensive analysis of bioenergetics and function of stimulated platelets in the presence of etomoxir, trimetazidine and oxfenicine, three pharmacologically distinct inhibitors of ß-oxidation. Each of them significantly impaired oxidative phosphorylation in unstimulated as well as thrombin-stimulated platelets leading to a small but consistent drop in ATP level in activated cells due to a lack of compensation from glycolytic ATP. Trimetazidine and oxfenicine attenuated platelet aggregation, P-selectin externalization and integrin αIIb ß3 activation. Both etomoxir and trimetazidine impeded agonist-induced dense granule release and platelet thrombus formation on collagen under arterial shear. The effect of inhibitors on platelet aggregation and dense granule release was dose- and incubation time- dependent with significant inhibition at higher doses and prolonged incubation times. Neither of the inhibitors could protect mice from collagen-epinephrine-induced pulmonary embolism or prolong mouse tail bleeding times. However, mice pre-administered with etomoxir, trimetazidine and oxfenicine were protected from ferric chloride-induced mesenteric thrombosis. In conclusion, ß-oxidation of fatty acids sustains ATP level in stimulated platelets and is therefore essential for energy-intensive agonist-induced platelet responses. Thus, fatty acid oxidation may constitute an attractive therapeutic target for novel antiplatelet agents.

Antithrombotic Activity of the Antiplatelet Agent Angipur on the Model of Arterial Thrombosis in Rats with Isoproterenol-Induced Myocardial Infarction.

We studied the effect of Angipur on the process of experimental thrombosis induced by damage to the carotid artery wall by surface application of 50% ferric chloride (III) solution in rats without comorbidities and with isoproterenol-induced myocardial infarction. In animals without comorbidities, Angipur administered intravenously was 1.2 times less effective, in terms of ED50, than the well-known inhibitor of GPIIb/IIIa platelet receptors tirofiban. However, under conditions of non-coronary myocardial infarction, Angipur significantly prolonged the time of thrombus formation and exhibited 1.4-fold higher activity than the reference drug tirofiban.

Risk of thrombocytopenia with glycoprotein IIb/IIIa inhibitors across drugs and patient populations: a meta-analysis of 29 large placebo-controlled randomized trials.

AIMS: Glycoprotein IIb/IIIa inhibitors (GPIs) reduce myocardial infarction and peri-procedural thrombotic complications in patients undergoing percutaneous coronary intervention (PCI); however, they may cause bleeding and thrombocytopenia, which are associated with poor clinical outcomes. Although the risk of bleeding has been well characterized, the extent of the risk of thrombocytopenia remains uncertain. In this meta-analysis, we aim to evaluate the risk of thrombocytopenia associated with GPI compared with placebo across drugs and patient populations. METHODS AND RESULTS: Risk ratios were calculated for thrombocytopenia (<100 000 platelets/mm(3)) and severe thrombocytopenia (<50 000 platelets/mm(3)) in 29 randomized large trials (>1000 patients) of GPI vs. placebo involving a total of 123 419 patients. We used meta-analysis techniques to estimate the summary effect across all trials, in pre-specified sub-groups, and in sensitivity analyses to assess the robustness of the data. Glycoprotein IIb/IIIa inhibitor use increases the rate of thrombocytopenia [risk ratio (RR) = 1.62, 95% confidence interval (CI) 1.48-1.78] and severe thrombocytopenia (RR = 3.52, 95% CI 2.87-4.30) compared with placebo. These findings are consistent by route of administration (oral vs. intravenous). Patients with ST-segment elevation myocardial infarction (RR 2.66, 95% CI 2.12-3.34) and elective PCI (RR 2.78, 95% CI 1.76-4.40) treated with a GPI had higher risks of thrombocytopenia than patients with non-ST-segment elevation acute coronary syndrome (RR 1.41, 95% CI 1.25-1.58; P < 0.001 for heterogeneity by sub-group). CONCLUSIONS: The administration of GPI compared with placebo was associated with a 63% increased risk of thrombocytopenia (<100 000 platelets/mm(3)), and >3-fold increased risk of severe thrombocytopenia (<50 000 platelets/mm(3)). This corresponds to an average of 10-20 additional cases of thrombocytopenia per 1000 patients given GPIs, of which 6-7 cases are severe.

Safety of "bridging" with eptifibatide for patients with coronary stents before cardiac and non-cardiac surgery.

Patients with previously implanted coronary stents are at risk for stent thrombosis if dual-antiplatelet therapy is prematurely discontinued. Bridging with a glycoprotein IIb/IIIa inhibitor has been advocated as an alternative, with few supporting data. The aim of this study was to determine the safety of such a strategy by retrospectively analyzing bleeding in 100 consecutive patients with previously implanted coronary stents who were bridged to surgery with eptifibatide after discontinuing thienopyridine therapy. A propensity-matched control comparison was performed for a subgroup of 71 patients who underwent cardiovascular surgery. Blood transfusions were required in 65% in the bridged group versus 66% in the control group (p = 0.86). The mean numbers of units transfused were 4.84 ± 6.93 and 3.65 ± 7.46, respectively (p >0.25). Rates of return to the operating room for bleeding or tamponade were 10% and 2.9%, respectively (p = 0.085). Increased rates of transfusion were noted for patients who received concomitant aspirin and/or intravenous heparin infusion. In conclusion, there does not appear to be any increase in the need for blood transfusions or rate of return to the operating room for patients being bridged with eptifibatide when thienopyridines are discontinued in the perioperative period, but concomitant use of additional antiplatelet or anticoagulant agents may increase transfusions and delays to surgery. Clinicians who are considering this strategy must weigh the risks of stent thrombosis versus bleeding.

Bivalirudin for primary percutaneous coronary intervention in acute myocardial infarction: the HORIZONS-AMI trial.

The combination of unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPIs) has been a frequently used anti-thrombotic treatment strategy for acute coronary syndrome patients, including those with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. However, the ischemic benefit of the UFH plus GPI combination came at the expense of high rates of bleeding complications and thrombocytopenia, both of which have been independently associated with increased mortality. By contrast, bivalirudin monotherapy compared with the combination of UFH plus GPI resulted in improved net clinical outcomes, based on similar ischemic protection with significant reductions in bleeding complications in randomized trials including patients with stable angina, those with unstable angina and those with non-ST-segment elevation myocardial infarction. More recently, the HORIZONS-AMI randomized, open-label, multicenter trial has compared the efficacy and safety of bivalirudin alone versus UFH plus a GPI in 3602 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Clinical results derived from this large study, including the final 3-year follow-up data, will be reviewed in the present clinical trial report.

Antiplatelet therapy in acute coronary syndromes.

Antiplatelet therapy is integral to the acute and long-term management of acute coronary syndromes (ACSs) and for minimizing the thrombotic complications of percutaneous coronary intervention (PCI). This article reviews the most commonly used antiplatelet agents in ACS therapy--aspirin, adenosine diphosphate (ADP)-receptor blockers, and glycoprotein IIb/IIIa inhibitors. More recent data are also reviewed on novel ADP-receptor blockers and thrombin inhibitors before addressing issues of adherence to antiplatelet regimens.

A risk score to predict bleeding in patients with acute coronary syndromes.

OBJECTIVES: The aim of this study was to develop a practical risk score to predict the risk and implications of major bleeding in acute coronary syndromes (ACS). BACKGROUND: Hemorrhagic complications have been strongly linked with subsequent mortality in patients with ACS. METHODS: A total of 17,421 patients with ACS (including non-ST-segment elevation myocardial infarction [MI], ST-segment elevation MI, and biomarker negative ACS) were studied in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) and the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trials. An integer risk score for major bleeding within 30 days was developed from a multivariable logistic regression model. RESULTS: Non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days occurred in 744 patients (7.3%) and had 6 independent baseline predictors (female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non-ST-segment elevation MI, or ST-segment elevation MI) and 1 treatment-related variable (use of heparin + a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) (model c-statistic = 0.74). The integer risk score differentiated patients with a 30-day rate of non-CABG-related major bleeding ranging from 1% to over 40%. In a time-updated covariate-adjusted Cox proportional hazards regression model, major bleeding was an independent predictor of a 3.2-fold increase in mortality. The link to mortality risk was strongest for non-CABG-related Thrombolysis In Myocardial Infarction (TIMI)-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality. CONCLUSIONS: Patients with ACS have marked variation in their risk of major bleeding. A simple risk score based on 6 baseline measures plus anticoagulation regimen identifies patients at increased risk for non-CABG-related bleeding and subsequent 1-year mortality, for whom appropriate treatment strategies can be implemented.

Prolonged infusion of eptifibatide as bridge therapy between bare-metal stent insertion and cardiovascular surgery: case report and review of the literature.

Dual antiplatelet therapy with aspirin and clopidogrel is the standard of care after coronary artery stent insertion. Clopidogrel, however, has been associated with an increased risk of bleeding if it is used before coronary artery bypass grafting (CABG), and current guidelines recommend that it be discontinued at least 5 days before surgery. Compared with dual antiplatelet therapy, single antiplatelet therapy or the combination of an antiplatelet agent and an anticoagulant is associated with an increased risk of subacute stent thrombosis. Management of patients who require semiurgent CABG after stent insertion presents a clinical challenge. Intravenous glycoprotein IIb-IIIa inhibitors provide antiplatelet coverage with a shorter duration of action; thus, in theory, they may be useful for these clinical situations. We describe a 47-year-old man who came to the emergency department with sudden-onset, retrosternal chest pain. An electrocardiogram confirmed a diagnosis of ST-segment elevation myocardial infarction. The patient underwent angioplasty and received a bare-metal stent. Because significant disease was revealed in other arteries, CABG was scheduled. Clopidogrel was discontinued in preparation for surgery, and the patient received an infusion of eptifibatide 2 microg/kg/minute as bridging therapy to surgery for a total of 9 days. No major hemorrhagic or clinically evident thrombotic complications occurred before or after the surgery. Eptifibatide may be safe and effective as bridging therapy for patients with intracoronary stents who require CABG.

HORIZONS trial: a step forward for primary percutaneous coronary intervention.

Bivalirudin has been associated with decreased bleeding, with similar rates of ischemia in patients with stable angina, unstable angina, non-ST elevation myocardial infarction and elective percutaneous coronary intervention (PCI). The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial tested whether with primary PCI, bivalirudin--compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor--reduced bleeding and net clinical benefit (bleeding, death, reinfarction, target-vessel revascularization for ischemia or stroke). Bivalirudin reduced major bleeding by 40% (4.9 vs 8.3%; risk ratio [RR]: 0.60; 95% confidence interval [CI]: 0.46-0.77; p < 0.0001) as compared with unfractionated heparin and a IIb/IIIa antagonist. Net adverse clinical events were reduced (9.2 vs 12.1%; RR: 0.76: 95% CI: 0.63-0.92; p = 0.005). Cardiac death and total death at 30 days were reduced with bivalirudin (1.8 vs 2.9%; p = 0.03) and (2.1 vs 3.1%; p = 0.047), and at 12 months (2.1 vs 3.8%; p < 0.005) and (3.4 vs 4.8%; p = 0.029), respectively. Bivalirudin reduced bleeding and net adverse clinical events as well as mortality compared with unfractionated heparin and a glycoprotein IIb/IIIa inhibitor. Bivalirudin is an attractive antithrombotic choice in patients undergoing primary PCI.

Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial).

OBJECTIVES: This prospective randomized trial evaluates the impact of early abciximab administration on angiographic and left ventricular function parameters. BACKGROUND: Glycoprotein IIb/IIIa inhibitors improve myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. METHODS: Two-hundred ten consecutive patients with first AMI undergoing primary PCI were randomized to abciximab administration either in the emergency room (early group: 105 patients) or in the catheterization laboratory, after coronary angiography (late group: 105 patients). Primary end points were initial Thrombolysis In Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and myocardial blush grade (MBG), as well as left ventricular function recovery as assessed by serial echocardiographic evaluations. RESULTS: Angiographic pre-PCI analysis showed a significantly better initial TIMI flow grade 3 (24% vs. 10%; p = 0.01), cTFC (78 +/- 30 frames vs. 92 +/- 21 frames; p = 0.001), and MBG 2 or 3 (15% vs. 6%; p = 0.02) favoring the early group. Consistently, post-PCI tissue perfusion parameters were significantly improved in the early group, as assessed by 60-min ST-segment reduction > or =70% (50% vs. 35%; p = 0.03) and MBG 2 or 3 (79% vs. 58%; p = 0.001). Left ventricular function recovery at 1 month was significantly greater in the early group (mean gain ejection fraction 8 +/- 7% vs. 6 +/- 7%, p = 0.02; mean gain wall motion score index 0.4 +/- 0.3 vs. 0.3 +/- 0.3, p = 0.03). CONCLUSIONS: In patients with AMI treated with primary PCI, early abciximab administration improves pre-PCI angiographic findings, post-PCI tissue perfusion, and 1-month left ventricular function recovery, possibly by starting early recanalization of the infarct-related artery.

An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards.

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death. We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting. A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%). Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes. The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors and clopidogrel alone and in combination in non-ST-segment elevation myocardial infarction (from the National Registry of Myocardial Infarction-4).

We investigated whether a combination of clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors safely decreases hospital mortality, reinfarction, and major bleeding beyond either therapy alone in patients with non-ST-elevation myocardial infarction (NSTEMI). GP IIb/IIIa inhibitors and clopidogrel, separately, have been shown to decrease adverse outcomes in patients with non-ST-elevation acute coronary syndromes, but the need for combination therapy is uncertain. Multivariate and propensity analyses compared the frequency of death, reinfarction, and major bleeding during hospitalization in 38,691 patients with NSTEMI who were enrolled in the National Registry of Myocardial Infarction 4 from July 2000 to December 2003. Of these, 65% received GP IIb/IIIa inhibitors only, 16.1% clopidogrel only, and 18.8% combination therapy. Among patients who did not undergo percutaneous coronary intervention (PCI), the composite end point of death, reinfarction, and major bleeding was significantly lower with combination therapy than with GP IIb/IIIa inhibitors alone (odds ratio 0.77, 95% confidence interval 0.67 to 0.88). In contrast, this composite end point was significantly higher when combination therapy was employed rather than clopidogrel alone (odds ratio 1.55, 95% confidence interval 1.33 to 1.81). However, among patients who underwent PCI, the composite end point was similar between combination therapy and GP IIb/IIIa inhibitor-only groups (odds ratio 1.01, 95% confidence interval 0.89 to 1.14). Further, there was a strong trend toward a higher composite end point among patients who received combination therapy rather than clopidogrel alone (odds ratio 1.31, 95% confidence interval 0.99 to 1.72). In conclusion, commonly employed strategies using a GP IIb/IIIa inhibitor alone or with the combination of clopidogrel plus GP IIb/IIIa inhibitor in NSTEMI may not be justified in comparison with a simpler strategy of clopidogrel used alone, especially in patients who have not undergone PCI.

Treating patients with acute coronary syndromes with aggressive antiplatelet therapy (from the Global Registry of Acute Coronary Events).

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.

Splenic rupture complicating periinterventional glycoprotein IIb/IIIa antagonist therapy for myocardial infarction in polycythemia vera.

Polycythemia vera is a myeloproliferative disorder predisposing to thromboembolic and bleeding complications. We report the case of a patient with polyglobuly, leukocytosis, and thrombocytosis, who suffered from acute ST-segment elevation myocardial infarction due to thrombotic high-grade pre-stent stenosis two months after percutaneous coronary intervention for complex coronary one vessel disease. Following re-PTCA and stent implantation in conjunction with periinterventional GP IIb/IIIa antagonist treatment, the patient was initially symptom free for about two hours before rapidly developing signs of a hemorrhagic shock. An abdominal CT scan showed splenic rupture with massive intraabdominal hemorrhage as a consequence of secondary bleeding into multiple pre-existing splenic infarctions. The patient's condition stabilized after emergency splenectomy. Subsequent bone marrow biopsy revealed the presence of polycythemia vera. Post-operatively, the patient was treated with the anti-platelet agents aspirin and clopidogrel to prevent subacute stent thrombosis. Additionally, cyto-reductive therapy with hydroxyurea was initiated because of a further increase in the platelet count. In patients with polycythemia vera, the indication for treatment with GP IIb/IIIa antagonists should be carefully weighed against the potentially serious bleeding complications. Should treatment be established, a risk stratification using abdominal sonography and bleeding time testing is recommended, while during treatment red blood count, platelet count, coagulation tests, and hemodynamic parameters should be closely monitored.

Access-site complications after rescue percutaneous coronary intervention during thrombolysis for acute myocardial infarction.

Aggressive antithrombotic medical therapy may increase the rate of access-site complications after percutaneous coronary intervention. Frequently, emergency coronary interventions have to be performed in a situation when thrombolysis therapy was administered as the first-line therapeutic approach in acute myocardial infarction but failed to achieve stable conditions. We analyzed the rate of femoral bleeding complications after emergency coronary intervention in 76 consecutive patients with unsuccessful thrombolysis in acute myocardial infarction. All invasive procedures were performed in a time period no longer than eight hours after thrombolysis was administered. Additional antithrombotic therapy with heparin and glycoprotein IIb/IIIa-inhibitors was given during intervention in 100% and 38.2% of patients, respectively. In three patients (3.9%) femoral hematomas without therapeutic consequences were documented; one patient (1.3%) developed a hematoma requiring blood transfusion. A pseudoaneurysm, fistula or surgical vascular intervention did not occur. Coronary interventional procedures in rescue situations can be performed with excellent safety with respect to access-site bleeding complications even under conditions of ongoing thrombolysis therapy and aggressive antithrombotic medical regimens.

Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade: a REPLACE-2 substudy.

OBJECTIVES: The purpose of this study was to assess if clopidogrel pretreatment affects the relative efficacy of bivalirudin versus heparin with glycoprotein (GP) IIb/IIIa blockade for percutaneous coronary interventions (PCI). BACKGROUND: Although thienopyridine pretreatment may improve clinical outcomes with PCI, it is unknown if bivalirudin's efficacy compared with heparin is dependent upon such pretreatment. METHODS: The Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events (REPLACE-2) trial was a double-blind, triple-dummy, randomized-controlled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI. The primary end point was a composite of death, myocardial infarction (MI), urgent revascularization at 30 days, and major in-hospital bleeding. The secondary end point was a 30-day composite of death, MI, and urgent revascularization. Clopidogrel pretreatment was encouraged (300 mg loading, 75 mg/day). RESULTS: Of 6,010 patients enrolled, 5,893 received clopidogrel, with 85.8% in the bivalirudin and 84.6% in the heparin group receiving clopidogrel pretreatment. Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the heparin group for both primary and secondary end points. Clopidogrel pretreatment did not affect the relative efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment duration. Pretreatment was associated with significantly lower primary end point with bivalirudin (8.7% pretreatment vs. 12.9% no pretreatment, p = 0.007), and nonsignificantly with heparin (9.7% vs. 11.7%, respectively, p = 0.20). Multivariable models showed a trend toward lower primary and secondary end points with clopidogrel pretreatment. CONCLUSIONS: Clopidogrel pretreatment at the doses and time administered in this trial did not influence the relative efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI. However, pretreatment was associated with a trend towards lower clinical events after PCI.

Glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia: clinical predictors and effect on outcome.

Glycoprotein IIb/IIIa inhibitors are used as an adjunct to antiplatelet therapy in percutaneous coronary intervention to reduce postprocedural enzyme elevations. Previous studies have shown a risk for thrombocytopenia that is associated with these agents. We sought to evaluate the incidence and outcomes of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia in an unselected series of patients undergoing percutaneous coronary intervention. We reviewed 984 interventions performed on 908 subjects over a specific time period. Glycoprotein IIb/IIIa inhibitors were used in 58.8% of cases. Their use increased from 38 to 82% during the study period (p < 0.0001). The incidence of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia was 5.4%. The occurrence of thrombocytopenia was not associated with higher age, gender or ethnicity. The preprocedural platelet count was not associated with induced thrombocytopenia (237 +/- 76 vs. 209 +/- 68 x 10(3), p > 0.05). The occurrence of thrombocytopenia was not associated with increased in-hospital mortality, 1-year mortality, myocardial infarction or revascularization, but was associated with a hospital stay twice as long as in those patients without thrombocytopenia (5.6 +/- 11.3 vs. 2.1 +/- 2.2 days, p < 0.001). Of the 5.4% of patients who developed thrombocytopenia, only 2 patients (7.1%) required platelet or blood cell transfusion.

Role of platelet glycoprotein IIb/IIIa inhibitors in rescue percutaneous coronary interventions.

In the setting of acute myocardial infarction, thrombolytic therapy fails to restore an adequate epicardial flow in a large number of patients. Although an increasing number of patients undergoes a percutaneous coronary intervention (PCI) after failed thrombolysis, this treatment has been poorly investigated. This review focuses particularly on the safety and prognostic impact of glycoprotein (GP) IIb/IIIa receptor inhibitors after failed thrombolysis. GPIIb/IIIa inhibitors have been demonstrated to improve the clinical outcome in patients undergoing primary PCI. However, the increased risk of bleeding with the administration of potent antiplatelet drugs after full-dose thrombolytics has limited the widespread use of GPIIb/IIIa inhibitors during rescue PCI. We recently reported that abciximab treatment during rescue PCI has a beneficial effect on the short-term prognosis, without excess bleeding complications. This result can be achieved by using the radial approach, a low-dose weight-adjusted heparin regimen, and by limiting the use of aortic counterpulsation. In conclusion, in case of thrombolysis failure, patients should be referred to tertiary hospitals where rescue PCI can be performed with expertise.