Use Of Platelet Glycoprotein Research Articles

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project.

Thrombus aspiration in ST-elevation myocardial infarction (STEMI) with high thrombus burden did not improve clinical outcomes. The clinical efficacy of the bailout use of platelet glycoprotein IIb/IIIa inhibitors (GPIs) in this clinical scenario remains unknown. We assessed associations between GPI use and in-hospital major bleeds, ischemic events, and mortality among STEMI patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration in a nationwide acute coronary syndrome registry (the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project). A total of 5896 STEMI patients who received thrombus aspiration were identified, among which 56.3% received GPI therapy. In a 1-to-1 propensity-score-matched cohort, compared with STEMI patients not treated with GPI, GPI use was associated with a 69% increase in major in-hospital bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on mortality (OR: 0.93, 95% CI: 0.55 to 1.58). However, among patients aged < 60years, GPI use was associated with a reduction in ischemic events (OR: 0.27, 95% CI: 0.08 to 0.98), and no significant increase in major bleeds was observed. In a nationwide registry, routine use of GPI following thrombus aspiration was not associated with reduced in-hospital ischemic events and mortality but at the cost of increased major bleeding. However, for patients aged < 60years, there may be a potential net benefit.

Abstract P426: Platelet Glycoprotein IIb/IIIa Inhibitors as an Adjunct to Stent Placement of Carotid Stenosis in Symptomatic Patients

Background: Intra-arterial or intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors have been used as adjunct to stent placement of carotid stenosis in patients with ischemic stroke or transient ischemic attack. Objective: To determine the proportion of patients with ischemic stroke or transient ischemic attack who received platelet GP IIb/IIIa inhibitors as adjunct to carotid stent placement and associated outcomes. Methods: We analyzed data from Cerner Health Facts® which collected data from participating facilities from January 1, 2000 to July 1, 2018. We identified patients with ischemic stroke or transient ischemic attack who underwent carotid stent placement for carotid stenosis and received Abciximab, Eptifibatide, or Tirofiban. Outcome was defined by discharge destination and classified into none to minimal disability, moderate to severe disability, or death. Results: A total of 8.4 % of 4567 patients with ischemic stroke or transient ischemic attack who underwent carotid stent placement for carotid stenosis received platelet GP IIb/IIIa inhibitors. Patients who received platelet GP IIb/IIIa inhibitors were more likely to experience cerebral ischemia (14.8% versus 7.5%) and undergo intubation/mechanical ventilation (4.4% versus 2%). There was a significant difference between patients who did or did not receive platelet GP IIb/IIIa inhibitors in terms of in hospital mortality rates (2.7% versus 1.2%, p=0.0152), none to mild disability (67.3% vs 75.7%, p=0.0003), and moderate to severe disability (30.1% vs 23.1%,p=0.0024). Conclusions: Adjunct use of platelet GP IIb/IIIa inhibitors in patients undergoing carotid stent placement for symptomatic carotid stenosis was associated with increased rates of in hospital mortality and moderate to severe disability.

Novel antiplatelet targets in the treatment of acute coronary syndromes

Acute coronary syndromes (ACS) are a global cause of mortality and morbidity that affect millions of lives worldwide. Following atherosclerotic plaque rupture, platelet activation and aggregation are the two major elements that initiate thrombus formation inside a coronary artery, which can obstruct blood flow and cause myocardial ischemia; ergo, antiplatelet therapy forms a major part of the treatment strategy for ACS. Patients with ACS routinely receive dual antiplatelet therapy (DAPT), which consists of aspirin and a platelet P2Y12 inhibitor to both treat and prevent atherothrombosis. Use of platelet glycoprotein (GP) IIb/IIIa inhibitors is now limited due to the risk of severe bleeding and thrombocytopenia. Thus, administration of GPIIb/IIIa inhibitors is generally restricted to bail out thrombotic events associated with PCI. Furthermore, current antiplatelet medications mainly rely on thromboxane A2 and P2Y12 inhibition, which have broad-acting effects on platelets and are known to cause bleeding, which especially limits the long-term use of these agents. In addition, not all ACS patients treated with current antiplatelet treatments are protected from recurrence of arterial thrombosis, since many platelet mechanisms and activation pathways remain uninhibited by current antiplatelet therapy. Pharmacological antagonism of novel targets involved in platelet function could shape future antiplatelet therapies that could ultimately lead to more effective or safer therapeutic approaches. In this article, we focus on inhibitors of promising targets that have not yet been introduced into clinical practice, including inhibitors of GPVI, protease-activated receptor (PAR)-4, GPIb, 5-hydroxytryptamine receptor subtype 2A (5-HT2A), protein disulfide isomerase, P-selectin and phosphoinositide 3-kinase β.

Efficacy and safety of tirofiban as an adjunctive therapy in patients with acute ST-segment elevation myocardial infarction undergoing percutaneous transluminal coronary angioplasty

Background: The introduction of stents and the use of platelet glycoprotein IIb/IIIa inhibitors, either alone or in combination with reduced-dose fibrinolytic therapy, has allowed percutaneous coronary intervention (PCI) to be performed more safely and synergistically following pharmacologic reperfusion therapy. Aims and Objectives: The present study was conducted to evaluate the efficacy and safety of tirofiban as an adjunct to angioplasty/stenting in acute ST-elevation myocardial infarction (MI) patients. Materials and Methods: A total of 156 consecutive patients diagnosed with acute ST-segment elevation MI (STEMI) presenting within 12 h of symptoms were randomly allocated to primary PCI alone or primary PCI along with tirofiban. Clinical characteristics, angiographic findings (including thrombolysis in MI [TIMI] flow rate), and ST-segment resolution were compared post-procedurally; left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, reinfarction, and target vessel revascularization) were compared at 30 days clinical follow-up. Results: Post-procedurally, TIMI Grade 3 reflow was significantly different between two groups (P = 0.01) and was associated with better in-hospital outcomes in tirofiban group compared with control group. Greater resolution of ST-elevation was achieved in patients given tirofiban than in non-tirofiban group, and the results were highly significant. Statistically significant improvement in LVEF was also observed in tirofiban group. There was non-significant difference in MACE and bleeding complications between two groups. Conclusion: Adjunctive tirofiban therapy for patients with acute STEMI, who underwent primary PCI, seems to be safe and effective treatment modality to achieve improved reperfusion, better LVEF, and clinical outcome at 30 days follow-up.

Incidence and Predictors of Early Left Ventricular Thrombus After ST-Elevation Myocardial Infarction in the Contemporary Era of Primary Percutaneous Coronary Intervention

The aim of this study was to define the incidence of left ventricular thrombus (LVT) and its predictors in the contemporary era of primary percutaneous intervention (pPCI) and contrast echocardiography. We retrospectively analyzed 1,059 patients presenting with ST-elevation myocardial infarction (STEMI) to our tertiary cardiac center and treated with pPCI. Preprocedural pharmacology and procedural technique (including access route, the use of drug-eluting stents, and thrombectomy) were at the operators' discretion. Transthoracic echocardiography was performed before discharge; echo contrast agent was used when appropriate. LVT was detected in 42 subjects (4%). There were no significant differences in baseline demographics or pre-PCI clinical features between the 2 groups. Post-treatment, mean ejection fraction (EF) in patients with LVT was 35±8.4% and in those without LVT was 47±10%, p<0.001. Thirty-seven patients (88%) in the LVT group presented with an anterior STEMI versus 471 patients (42%) in the without LVT group (p<0.001). Apical akinesis was noted in all patients with LVT irrespective of the principal location of the MI. Multivariate analysis predictors of LVT were reduced EF, anterior site of MI, and the use of platelet glycoprotein IIb/IIIa inhibitors. After diagnosis of LVT, patients were treated with warfarin for 3 to 6 months. No significant difference in mortality was detectable at discharge between the 2 groups. In conclusion, in the contemporary era of pPCI, the incidence of LVT in patients with STEMI is significantly lower than that of the previous (thrombolysis) literature. The early presence of LVT is more likely in patients with anterior STEMI (involving the apex) and reduced EF.

Optimal Use of Platelet Glycoprotein IIb/IIIa Receptor Antagonists in Patients Undergoing Percutaneous Coronary Interventions

Discovery of the central role of platelets in the pathogenesis of acute coronary syndromes (ACS) and ischaemic complications of percutaneous coronary interventions (PCI) has led to the widespread use of oral and parenteral platelet inhibitors to treat these conditions. Glycoprotein (GP) IIb/IIIa (also known as α(IIb)β(3)) receptors on the surface of platelets play an essential role in platelet aggregation and serve as a key mediator in the formation of arterial thrombus. When activated, GP IIb/IIIa receptors bind to fibrinogen, which serves as the 'final common pathway' in platelet aggregation. Of the numerous agents developed for modulating platelet activity, intravenous platelet GP IIb/IIIa receptor antagonists are the most potent. There are four agents in clinical use, including abciximab, eptifibatide, tirofiban and lamifiban, although lamifiban is not approved for use in the US. While all agents block fibrinogen binding to GP IIb/IIIa, they do so by different mechanisms. Abciximab is a humanized form of a murine monoclonal antibody directed against GP IIb/IIIa, eptifibatide is a synthetic, cyclic heptapeptide that contains a lysine-glycine-aspartic acid (KGD) sequence that mimics the arginine-glycine-aspartic acid (RGD) sequence found on GP IIb/IIIa, tirofiban is a non-peptide antagonist derived by optimization of the tyrosine analogue that structurally mimicks the RGD-containing loop of the disintegrin echistatin, and lamifiban is a synthetic, non-cyclic, non-peptide, low-molecular-weight compound. In clinical trials, use of these agents reduces ischaemic adverse cardiovascular events in patients with ACS undergoing PCI, but at a cost of increased bleeding.

Safety and feasibility of intraarterial eptifibatide as a revascularization tool in acute ischemic stroke

Experience with the use of platelet glycoprotein (GP) IIb-IIIa inhibitor eptifibatide in patients with ischemic stroke is limited. The authors report the off-label use of intraarterial eptifibatide during endovascular ischemic stroke revascularization procedures for reocclusion after documented recanalization or formed fresh thrombi in distal vessels that were inaccessible to endovascular devices. Patients who received intraarterial eptifibatide were identified from a prospectively collected database of patients in whom endovascular revascularization for acute ischemic stroke was attempted between 2005 and 2008. Data were analyzed retrospectively. The intraarterial eptifibatide dose was a single-bolus dose of 180 μg/kg body weight. Primary outcome measures were angiographic recanalization (Thrombolysis in Myocardial Infarction Grade 2 or 3), symptomatic intracranial hemorrhage rate, overall mortality rate, and favorable 3-month modified Rankin Scale score (≤ 2). The study included 35 patients (mean age 62 years, range 18-85 years). The median presenting National Institutes of Health Stroke Scale score was 13. Two patients received intravenous tissue plasminogen activator before endovascular therapy. The median time from symptom onset to therapy initiation was 230 minutes (range 90-1370 minutes). Twelve patients (34%) received intraarterial tissue plasminogen activator without mechanical measures. Mechanical revascularization measures used were Merci retriever in 19 (54%), Penumbra device in 1 (3%), balloon angioplasty in 15 (43%), and stent placement in 22 (63%) patients. The mean dose of intraarterial eptifibatide was 11.6 mg (range 5-16.6 mg). Partial-to-complete recanalization (Thrombolysis in Myocardial Infarction Grade 2 or 3) was achieved in 27 patients (77%). Postprocedure intracranial hemorrhage occurred in 13 patients (37%), causing symptoms in 5 (14%). In the 5 symptomatic intracranial hemorrhage cases, all patients but one presented more than 8 hours after symptom onset and all received intraarterial recombinant tissue plasminogen activator. The median discharge National Institutes of Health Stroke Scale score was 7 (range 0-17). At 3 months postprocedure, 21 patients (60%) had a modified Rankin Scale score ≤ 2, and 8 patients (23%) had died. Adjunctive intraarterial eptifibatide is a feasible option for salvage of reocclusion and thrombolysis of distal inaccessible thrombi during endovascular stroke revascularization. Its safety and efficacy need to be studied further in larger, multicenter, controlled studies.

Estudio aleatorizado con abciximab o eptifibatide en angioplastia coronaria compleja. Resultados intrahospitalarios y a 30 días

Introduction and objectives The use of platelet glycoprotein IIb/IIIa inhibitors (IGP) in patients undergoing high risk percutaneous coronary angioplasty (PCA) is increasing. In this prospective randomized study we compare abciximab (ABX) vs eptifibatide (EPT). The primary endpoints were to compare the incidence of major adverse events during the first month after PCA (death, stroke, the need for revascularisation, and myocardial infarction) and vascular complications in both groups. Methods A total of 208 patients were recruited, and received abciximab (103) or eptifibatide (105) after the coronary angioplasty. Patients with non-ST acute coronary syndrome or angina with multivessel coronary disease and complex lesions were included. Patients with ST-segment elevation myocardial infarction of less than 24 h of clinical progression were excluded. Results Clinical characteristics and baseline angiographic findings were similar in ABX and EPT: diabetic: 35.9 versus 37.1%; multivessel coronary disease 79.6 vs 76.1%, respectively ( P=ns). No difference was observed in major adverse events: ABX 22 patients (21%) vs EPT 26 (24%), ( P=0.5). There was a death in the ABX group, probably due to a stent thrombosis at 15 days after PCA: Myocardial Infarction (Troponin I >1 ng/dl): 21 versus 26 patients ( P=0.45). There were some vascular complications in 8 patients on ABX and 4 on EPT ( P=0.22). There were no haemorrhagic complications or major bleeding. One minor and 3 slight bleedings were reported in each group. Conclusions No difference was observed between ABX and EPT in major adverse events during the first month after PCA, and there was a small percentage of bleeding complications in both groups.

Use of platelet glycoprotein IIb/IIIa inhibitors in diabetics undergoing PCI for non-ST-segment elevation acute coronary syndromes: impact of clinical status and procedural characteristics

BackgroundThe most recent ESC guidelines for percutaneous coronary intervention (PCI) recommend the use of glycoprotein IIb/IIIa inhibitors (GPI) in high risk patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), particularly in diabetics. Little is known about the adherence to these guidelines within Europe.Methods and resultsBetween May 2005 and April 2008 a total of 47,407 consecutive patients undergoing PCI were prospectively enrolled into the PCI-Registry of the Euro Heart Survey Programme. In the present analysis we examined the use of GPI in 2,922 diabetics who underwent PCI for NSTE-ACS. In this high risk population only 22.2% received a GPI; 8.9% upstream and 13.4% during PCI. The strategy of the individual institution had a major impact on the usage of GPI. In the multiple regression analysis clinical instability and complex lesion characteristics were strong independent determinants for the use of GPI, whereas renal insufficiency was negatively associated with its use. After adjustment for confounding variables no significant differences in hospital mortality could be observed between the cohorts, but a significantly higher rate of non-fatal postprocedural myocardial infarction was observed among patients receiving GPI upstream.ConclusionsDespite the recommendation for its use in the current ESC guidelines, only a minority of the diabetics in Europe undergoing PCI for NSTE-ACS received a GPI. The use of GPI was mainly triggered by high-risk interventional scenarios.

AS-98: Thrombus Aspiration during Primary Percutaneous Coronary Intervention Improves Myocardial Reperfusion with and without Use of Platelet Glycoprotein IIb/IIIa Receptor Blockers

Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with ST-segment elevation myocardial infarction. However, myocardial reperfusion following primary PCI (pPCI) is limited by microembolism and atherothrombotic events. Platelet glycoprotein (GP) IIb/IIIa receptor blockers and thrombus aspiration both reduce the incidence of such events during PCI. This was a prospective, randomized study intended to compare effectiveness of upstream use of Clotinab (a product made in Isu Abxis), aspiration devices, and both strategies in reducing microembolic complications during pPCI.

Reperfusion Strategies in Acute ST-Elevation Myocardial Infarction: An Overview of Current Status

Several randomized trials and meta-analyses have shown that primary angioplasty is superior to thrombolysis in the treatment of ST-segment elevation myocardial infarction (MI) in terms of death, reinfarction, and stroke. However, primary angioplasty should be regarded as the preferred strategy as long as it can not be applied with a reasonable time delay to treatment, as compared with the administration of thrombolysis. In fact, time-to-treatment has been shown to be a determinant of survival not only for thrombolysis but also for primary angioplasty. Recent guidelines consider a time from first medical contact to PCI of 90 minutes or a PCI-related delay of 60 minutes as reasonable cutoffs to identify the best reperfusion strategy. The beneficial effects of primary angioplasty could be expected particularly after the first 3 hours from symptom onset, when thrombolysis, particularly streptokinase, may be less effective, whereas within the first 3 hours, thrombolysis (started in the prehospital setting, preferably) may represent a valid therapeutic option. Because the survival benefits of primary angioplasty depends on the patient's risk profile and timely application of reperfusion, we would suggest, among patients in the first hours from symptom onset, a strategy of early pharmacologic reperfusion and transfer to primary PCI centers, where the decision of performing angiography acutely may be based on the assessment of myocardial reperfusion and risk profile, whereas after the first 3 hours from symptoms onset, primary angioplasty should be considered the preferred strategy if applicable, particularly in regions when streptokinase still represents the only available lytic therapy. However, even though primary angioplasty is able to achieve thrombolysis and TIMI 3 flow in most patients, a still relevant proportion of patients experience poor myocardial reperfusion, with negative impact on acute and long-term survival. The use of platelet glycoprotein IIb/IIIa complex inhibitors has significantly improved survival, with additional benefits obtained by early administration aiming at early reperfusion, which are to be recommended, particularly among high-risk patients and those presenting within the first hours from symptom onset. The use of adjunctive mechanical devices has reduced the incidence of distal embolization without any apparent benefit in survival. Until the results of larger randomized trials become available, these devices may be considered in patients at high risk for distal embolization, such as those with large thrombotic burden. The use of coronary stenting has significantly reduced restenosis, as compared with balloon angioplasty. Several randomized trials have recently been conducted on drug-eluting stents in ST-segment elevation MI, showing the safety and significant benefits of these devices in terms of restenosis, as compared with bare metal stents (BMSs). However, because of unpredictable compliance to long-term double oral antiplatelet therapy in acute patients, caution should be taken with extensive use of drug-eluting stents in primary angioplasty.

Management of recurrent cerebral arterial occlusion in a patient with cardiac decompensation

We describe a woman with congestive heart failure who presented with acute cardiac decompensation followed by ischemic stroke. The management of the patient posed unique challenges for thrombolytic treatment (due to existing coagulopathy) and subsequent optimization of hemodynamic status. Issues related to rethrombosis and use of platelet glycoprotein IIB/IIIA inhibitors are also discussed.

Impacto do diabetes mellitus na mortalidade em síndromes coronarianas agudas

Diabetes mellitus (DM) is a leading cause of mortality in the world, mainly on account of cardiovascular diseases. At present we know that not only DM but also other hyperglycemic states are a risk factor for coronary arterial disease. In the context of acute coronary syndromes, DM determines a worst prognosis, either in short- or long-term outcomes. Since the absolute risk of death is greater among diabetic patients when compared to non-diabetic patients, therapeutical interventions have a greater impact in terms of benefits to these patients as well. Strategies such as strict control of hyperglycemia during hospitalization, acute reperfusion management (either by thrombolysis or by percutaneous coronary intervention), use of platelet glycoprotein IIb/IIIa inhibitors and angiotensin-converting enzyme (ACE)-inhibitors have recently proven to be of greater benefit for diabetics over non-diabetic patients. Meanwhile, in spite of all proven benefits of the use of evidence-based interventions to the treatment of acute coronary syndromes on diabetic patients, there is still an under utilization of these measures. Therefore, taking into account the predictions of an increasing number of diabetics in the world for the future years, and the fact that acute coronary syndromes will be the leading cause of death among them, it becomes increasingly necessary for both cardiologists and endocrinologists to work together in order to reduce the unfavorable outcomes that are expected to arise.

Use of Platelet Glycoprotein IIb/IIIa Inhibitors in Saphenous Vein Graft Percutaneous Coronary Intervention and Clinical Outcomes

Platelet glycoprotein (GP) IIb/IIIa inhibitors are widely used in percutaneous coronary intervention (PCI). Previous studies have suggested that they do not offer benefit in saphenous vein graft PCI. Nonetheless, their use remains widespread during vein graft angioplasty. We retrospectively analyzed 1,537 patients who underwent saphenous vein graft PCI. Patients who received a GP IIb/IIIa inhibitor (n = 941) were compared with those who did not receive any GP IIb/IIIa inhibitor (n = 596). The primary end point was myonecrosis after PCI (creatine kinase-MB level >3 times the upper reference limit). The incidence of myonecrosis after PCI was similar between the group that received GP IIb/IIIa and the group that did not (odds ratio for GP IIb/IIIa use 1.39, 95% confidence interval 0.97 to 2.00, p = 0.07). Propensity-adjusted analysis demonstrated no significant difference in myonecrosis after PCI, in-hospital mortality, Q-wave myocardial infarction, or bleeding (blood transfusion, retroperitoneal bleed, or hematoma) between the 2 groups. In an analysis restricted to patients who were treated with an emboli protection device, GP IIb/IIIa use was not associated with decreased myonecrosis after PCI (this was also the case for patients who were not treated with an emboli protection device). Unadjusted survival (mean follow-up 5.5 +/- 0.1 years) was similar between the group that received GP IIb/IIIa and the group that did not (log-rank test, p = 0.89). There was no difference in survival after adjusting for the propensity to receive a GP IIb/IIIa inhibitor (adjusted odds ratio for GP IIb/IIIa use 0.92, 95% confidence interval 0.69 to 1.23, p = 0.59). In conclusion, adjunctive use of platelet GP IIb/IIIa inhibitors in saphenous vein graft PCI does not appear to be associated with less myonecrosis or improved survival.

Equipoise in the Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial (ESPRIT): a critical appraisal

Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial (ESPRIT) was a multicenter randomized controlled clinical trial in which participants were randomized between eptifibatide and placebo. A "clinical hold" was initially placed on the trial by the US Food and Drug Administration (FDA), which was concerned about the placebo-only control arm. The hold was lifted after additional information concerning the use of platelet glycoprotein IIb/IIIa inhibitors in clinical practice, derived from a survey of interventional cardiologists, was provided. The trial's principal investigator and colleagues have described how these issues were resolved, and advance a claim of equipoise for the trial. In this critical appraisal we examine the information and arguments proffered in support of the trial design and conclude that they evidence a misunderstanding of equipoise. We believe that a placebo-only control arm was not justified by the information provided by the trialists.

Use of Bivalirudin During Percutaneous Coronary Intervention in Patients With Diabetes Mellitus: An Analysis From the Randomized Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial

The objective of this study was to confirm that the efficacy and safety of percutaneous coronary intervention (PCI) in diabetic patients are not compromised by a bivalirudin-based antithrombotic strategy. Previous studies have shown a survival benefit with use of platelet glycoprotein (GP) IIb/IIIa inhibitors in diabetic patients undergoing PCI. The Randomized Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial showed the non-inferiority of a strategy of bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. The relative efficacy of these two strategies in diabetic patients has not been studied. We evaluated the diabetic patients enrolled in the REPLACE-2 trial to assess the impact of these antithrombotic strategies on the short- and long-term outcome after PCI. The REPLACE-2 trial enrolled 1,624 diabetic patients and 4,368 non-diabetic patients. Compared with non-diabetic patients, diabetic patients had similar short-term outcome but higher mortality at 1 year (3.06% vs. 1.85%, p = 0.004). There was no difference in short-term or long-term ischemic events among the diabetic patients randomized to the two arms. Specifically, the 1-year mortality rate was non-significantly lower in the bivalirudin arm, suggesting no differential survival impact of the two strategies (2.3% vs. 3.9%). There was less minor bleeding in the bivalirudin arm in diabetic patients (12.6% vs. 24.4%, p < 0.001), whereas no difference was seen in the incidence of major bleeding (3.0% vs. 3.3%, p = 0.69). Compared with routine GP IIb/IIIa inhibition, the use of bivalirudin with provisional GP IIb/IIIa inhibitors in diabetic patients is associated with no differences in clinical outcomes at 30 days, a trend toward lesser mortality at 1 year, and a reduction in minor bleeding.

Pharmacodynamics and pharmacokinetics of the platelet GPIIb/IIIa inhibitor tirofiban in patients undergoing percutaneous coronary intervention: implications for adjustment of tirofiban and clopidogrel dosage

Introduction Despite extensive data supporting the use of platelet glycoprotein (GP) IIb/IIIa (GPIIb/IIIa) inhibitors in the therapy of patients with acute coronary syndromes (ACS), there is considerable debate as to the optimal choice of antiplatelet regimen. The objective of this study was to conduct a detailed time-resolved analysis of the effects of the GPIIb/IIIa inhibitor tirofiban with concomitant clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) to improve the dosing regimen of these two commonly used antiplatelet drugs. Methods The study was performed in 14 patients with non-ST-segment elevation (NSTE) ACS who underwent PCI while being treated with the current typically utilized regimen of tirofiban (10 μg/kg bolus, 0.15 μg/kg/min infusion) and clopidogrel (300 mg). Platelet function was assessed before, during, and after tirofiban infusion using a panel of agonists for ADP receptors, PAR1 and PAR4 thrombin receptors, and collagen receptors. Results Measurements of circulating tirofiban levels demonstrated a trough, which paralleled a reduction in platelet inhibition for all platelet agonists during the time when PCI was being performed. Interestingly, younger ACS patients (<55 years) exhibited less inhibition of platelet function both during the PCI procedure and after termination of the tirofiban infusion. These apparent age differences were primarily attributed to a decreased responsiveness of the younger patients to clopidogrel. Conclusions This study shows that the currently utilized tirofiban dosage is suboptimal and suggests that patients may benefit from a higher dose regimen.

Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting: Risk factors, prevention, and treatment

ObjectivesThe study defined the incidence of cerebral hyperperfusion syndrome and intracranial hemorrhage (ICH) and the risk factors for their development following carotid artery stenting (CAS). BackgroundHyperperfusion syndrome and ICH can complicate carotid revascularization, be it endarterectomy or CAS. Although extensive effort has been devoted to reducing the incidence of ischemic stroke complicating CAS, little is known about the incidence, etiology, and prevention strategies for hyperperfusion and ICH following CAS. MethodsWe retrospectively reviewed the prospective database of 450 consecutive patients who were treated with CAS in our department to identify patients who developed hyperperfusion syndrome and/or ICH. ResultsThe mean age of the patients was 72.7 ± 10.9 years, and the mean diameter narrowing was 84 ± 12.8%. Five (1.1% [95% confidence interval 0.4% to 2.6%]) patients developed hyperperfusion. Three (0.67%) of the five developed ICH. Two of these patients died (0.44%). Symptoms developed within a median of 10 h (range, 6 h to 4 days) following stenting. All five patients had correction of a severe internal carotid stenosis (mean 95.6 ± 3.7%) with a concurrent contralateral stenosis >80% or contralateral occlusion and peri-procedural hypertension. These same risk factors are involved in cerebral hyperperfusion following carotid endarterectomy. The use of platelet glycoprotein IIb/IIIa receptor blockers did not appear to increase the risk ICH. ConclusionsThe hyperperfusion syndrome occurs infrequently following CAS, and ICH occurs in 0.67% of patients. Patients with severe bilateral carotid stenoses may be predisposed to ICH, particularly if there is concurrent arterial hypertension. Patients with these factors may require more intensive hemodynamic monitoring after CAS, including prolongation of hospitalization in some cases.

Acute myocardial infarction: Fibrinolytic therapy

Fibrinolytic therapy (also known as thrombolytic therapy) is an established, simple, widely available and cost-effective treatment option for acute myocardial infarction. Adjunctive use of antiplatelet and antithrombin therapies has been shown to reduce reinfarction rates by 30% to 40%. These agents may also improve reperfusion rates and facilitate percutaneous coronary intervention (PCI). Adjunctive use of platelet glycoprotein IIb/IIIa inhibitors and newer antithrombotic agents (eg, low molecular weight heparin, bivalirudin, or pentasaccharide) has not been shown to reduce 30-day mortality rates. Bolus administration of fibrinolytic agents enhances their acceptability for prehospital use, and dose adjustment of antithrombotic therapy may help to reduce the risk of bleeding, particularly in lighter-weight patients and the elderly. There is a need for trials comparing newer fibrinolytic regimens with primary PCI and facilitated PCI. The time from symptom onset to reperfusion is the most important factor affecting patient outcome.

Abciximab Adds No Benefit to Clopidogrel in Low- and Intermediate-Risk PCI

Routine use of platelet glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) has shown the greatest benefits in patients with high risk for complications and in those with inadequate platelet antagonism. Now, in a partially industry-supported, multicenter, double-blind trial, researchers randomized 2159 low- and intermediate-risk patients (>95% in Europe) to placebo or the GPIIb/IIIa inhibitor abciximab. …