Glycoprotein IIb-IIIa Antagonists Research Articles

Effects of Antiplatelet Drugs on Platelet-Dependent Coagulation Reactions.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist), or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen and sedimented in multiwell plates, and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, prolonged the lag phase and decreased the maximum rate of plasma clotting and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

Inhibition of Src but not Syk causes weak reversal of GPVI-mediated platelet aggregation measured by light transmission aggregometry

Src tyrosine kinases and spleen tyrosine kinase (Syk) have recently been shown to contribute to sustained platelet aggregation on collagen under arterial shear. In the present study, we have investigated whether Src and Syk are required for aggregation under minimal shear following activation of glycoprotein VI (GPVI) and have extended this to C-type lectin-like receptor-2 (CLEC-2) which signals through the same pathway. Aggregation was induced by the GPVI ligand collagen-related peptide (CRP) and the CLEC-2 ligand rhodocytin and monitored by light transmission aggregometry (LTA). Aggregation and tyrosine phosphorylation by both receptors were sustained for up to 50 min. The addition of inhibitors of Src, Syk or Bruton’s tyrosine kinase (Btk) at 150 sec, by which time aggregation was maximal, induced rapid loss of tyrosine phosphorylation of their downstream proteins, but only Src kinase inhibition caused a weak (~10%) reversal in light transmission. A similar effect was observed when the inhibitors were combined with apyrase and indomethacin or glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, eptifibatide. On the other hand, activation of GPIIb-IIIa by GPVI in a diluted platelet suspension, as measured by binding of fluorescein isothiocyanate-labeled antibody specific for the activated GPIIb-IIIa (FITC-PAC1), was reversed on the addition of Src and Syk inhibitors showing that integrin activation is rapidly reversible in the absence of outside-in signals. The results demonstrate that Src but not Syk and Btk contribute to sustained aggregation as monitored by LTA, possibly as a result of inhibition of outside-in signaling from GPIIb-IIIa to the cytoskeleton through a Syk-independent pathway. This is in contrast to the role of Syk in supporting sustained aggregation on collagen under arterial shear.

Thrombocytopenia induced by glycoprotein (GP) IIb-IIIa antagonists: about two cases

In this paper, we report two cases of induced thrombocytopenia after the infusion of glycoprotein (GP) IIb/IIIa receptors antagonists, following a coronary angioplasty. The first patient is a 65-year-old woman, admitted with acute coronary syndrome requiring percutaneous angioplasty with stenting. The patient was given tirofiban + unfractionated heparin (UFH). Ten hours later, the patient revealed very severe thrombocytopenia and went into hemorrhagic shock (hematemesis and hematoma at the injection site). The patient was transfused with nine units of red blood cells (RBCs), 24 platelets pellets and 4 units of fresh frozen plasma (FFP). The second patient is a 76-year-old woman. She was admitted to hospital for acute coronary syndrome necessitating percutaneous angioplasty with stenting and a glycoprotein IIb/IIIa receptor antagonists, tirofiban + unfractionated (UFH). Four hours later, the patient presented with gingivorrhagia associated thrombocytopenia. She received six platelet pellets transfusion with well clinical and biological improvement. These two observations raise the significance of a close monitoring of platelet count after the initiation of GP IIb/IIIa antagonists infusion, which are sometimes responsible for life-threatening adverse events.

Antiplatelet Therapy in Patients with Acute Coronary Syndrome: An Update

Antiplatelet therapy is the cornerstone in the treatment of acute coronary syndrome. Aspirin is the most widely used antiplatelet agent followed by P2Y12 inhibitors. Glycoprotein (GP) IIb-IIIa antagonists are also gaining popularity as an antiplatelet agents during peri-PCI period. This review article summarizes the indications, duration of dual antiplatelet therapy (DAPT) in ACS setting. Antiplatelet therapy in special situations like atrial fibrillation and thrombocytopenia are discussed here. Issues like switching between P2Y12 inhibitors and genetic testing of antiplatelet agents are also mentioned in this article
 University Heart Journal Vol. 17, No. 1, Jan 2021; 66-70

Effects of two different glycoprotein platelet IIb/IIIa inhibitors and the clinical endpoints in patients with intracranial Pipeline flow diverter implant

ObjectiveTo compare the antiplatelet effect and major adverse cerebrovascular events of Pipeline for intracranial aneurysms using glycoprotein IIb/IIIa antagonists (GPI) eptifibatide and tirofiban. MethodsRetrospective analysis of relevant data of patients using GPIs combined with oral antiplatelet therapy in Nanfang Hospital of Southern Medical University from December 2017 to December 2019. The study was approved by the ethics Committee of Nanfang Hospital of Southern Medical University. According to the random use of GPIs drugs, they were assigned to the eptifibatide group and tirofiban group. Basic data, platelet inhibition rates at baseline, 24h and 72h after administration, short-term major adverse cerebrovascular events, and bleeding complications were compared between the two groups. ResultsA total of 47 patients were included in this study, including 24 patients in eptifibatide group and 23 patients in tirofiban group. There was no significant difference in average age (53.75 vs. 53.91 years) and body mass index (BMI) (24.39 vs. 22.73 ​kg/m2) between eptifibatide group and tirofiban group. There was no significant difference in coagulation factor function (R), fibrinogen function (K), fibrinolysis function (EPL), comprehensive coagulation index (Cl), arachidonic acid pathway inhibition rate (AA%) and adenosine diphosphate inhibition rate (ADP%). However, the baseline level of residual platelet function MA (ADP) in eptifibatide group was significantly higher than that in tirofiban group (50.79 vs. 35.29 ​mm, P ​= ​0.0026). There was a statistical difference in the platelet aggregation function MA (65.38 vs. 62.54 ​mm, p ​= ​0.0442), the rate of spontaneous hemorrhagic stroke (4.3% vs. 0%) and the rate of asymptomatic minor bleeding (26.08% vs. 4.1%) in the two groups (P ​< ​0.05). ConclusionBoth eptifibatide and tirofiban can effectively inhibit platelets, but the effect of etifeptide is better than that of tirofiban in preventing intracranial microhemorrhage and asymptomatic cerebral infarction.

Prolonged enoxaparin therapy compared with standard-of-care antithrombotic therapy in opiate-treated patients undergoing primary percutaneous coronary intervention

A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (1:1) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding: one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients.

Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction

Morphine can delay absorption of P2Y12-inhibitors in ST-elevation myocardial infarction (STEMI) patients, which has the potential to expose these patients to increased stent thrombosis risk after primary percutaneous coronary intervention (PPCI). Limited evidence exists for pharmacotherapeutic strategies aiming to mitigate this risk. We evaluated the impact of guideline-driven ‘routine’ glycoprotein IIb/IIIa antagonist (GPI) use in morphine-treated patients undergoing PPCI. A total of 3224 consecutive STEMI patients undergoing PPCI at a large tertiary cardiac center between 2012 and 2017 were evaluated. GPI use and outcomes before and after introduction of a local guideline were compared, and rates of definite stent thrombosis were identified at 24 h and 30 days. GPI use increased from 42.4% to 69.9% after the introduction of the new guideline. Stent thrombosis occurred in 1.3% (26/1947) pre-guideline and 0.6% (7/1244) post-guideline (P = .037). Of the 33 stent thrombosis cases, 90% (27/30) had received morphine, of whom 85.2% (23/27) had not received adjunctive GPI. Complete records for assessing 30-day bleeding rates were only available in 374 patients and, in this subset, there was no significant difference in rates of GUSTO moderate or severe bleeding before vs. after introduction of the local guideline (1.7% vs 2.8%; P = .47) although, in both cohorts combined, any GUSTO bleeding was observed more frequently in GPI-treated patients (21.8%) compared to those not receiving a GPI (10.0%; P = .002). In conclusion, routine GPI use in morphine-treated STEMI patients undergoing PPCI appears to protect against stent thrombosis. Large-scale studies are needed to establish the overall risk-benefit of GPI therapy in morphine-treated PPCI patients and to assess alternative strategies for preventing acute stent thrombosis in these patients.

Anticoagulation during Cardiopulmonary bypass in Patients with Heparin-Induced Thrombocytopenia using Heparin and the Platelet Glycoprotein IIb-IIIa Antagonist

Anticoagulation during Cardiopulmonary bypass in Patients with Heparin-Induced Thrombocytopenia using Heparin and the Platelet Glycoprotein IIb-IIIa Antagonist

Abstract 19565: The Safety and Efficacy of Platelet Glycoprotein Iib Iiia Antagonist by Intracoronary Administration versus Intravenous Administration in Patients With St Segment Elevation Myocardial Infarction: A Meta-analysis

Objective: Evaluate the administration (IC) and intravenous(IV) administration of platelet glycoprotein IIb / IIIa antagonist in STEMI patients. Methods: We searched PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library, the retrieval time is May 2015. The papers which compared the safety and efficacy of IC and IV STEMI patients with platelet glycoprotein IIb / IIIa antagonist were included.Two researchers evaluated the trails and collected data according to 5.0.2 Cochrane Handbook. The data were merged by RevMan 5.0 software. Results: Finally we included 17 RCTs(n=8279, including 4260 IC administration patients, and 4019 IV administration patients). The GP IIb / IIIa antagonist was injected in the coronary after stent releasing during PCI in the IC group. Meta analysis showed: In the STEMI trials, intracoronary group had better clinical outcomes than intravenous group in the following index: short time MACE (one month after PCI) [OR=0.47,95%CI:0.23-0.97], congestive heart failure [OR=0.59,95%CI:0.41-0.84], left ventricular ejection fraction [MD=1.11, 95%CI: 0.48-1.74], infarct size [MD=-1.00, 95%CI: -1.65~ -0.35], myocardial blush grade 3 [OR=1.60, 95%CI: 1.12-2.27], drug occupational rate [OR=4.16, 95%CI: 1.45-11.92], wall motion score index[MD=-0.27,95%CI: -0.51~ -0.03]. And the IC and IV group were similar in the death, long time MACE(1 year after PCI), stent thrombosis, sever bleeding, ST-segment resolution -1 month after PCI, target vessel revascularization, myocardial infarction recurrence, TIMI grade 3 after PCI, left ventricular end systolic volume, left ventricular end diastolic volume, intervention success rate, life threatening arrhythmia, stroke after PCI, CK-MB, operation time, E/ A, cardiac death, minor bleeding, with no significant difference (P&gt; 0.05). Conclusions: This updated meta-analysis shows, compared to the IV, IC administration of platelet glycoprotein IIb / IIIa antagonist could reduce the risk of short time MACE (one month after PCI), congestive heart failure, and improve left ventricular ejection fraction, so IC administration of platelet glycoprotein IIb / IIIa antagonist could be a considerable way to be used in STEMI patients.

PP.LB03.24

Objective: Obesity is a risk factor for cardiovascular disease and mortality, however several studies have been reported that patients with obesity who have admitted with acute myocardial infarction or have undergone percutaneous coronary intervention (PCI) have better clinical outcomes than their normal weight counterparts. The impact of body mass index (BMI) on myocardial perfusion and early clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients revascularized totally with manual thrombus aspiration remains unclear. Design and method: The study included 94 consecutive patients who underwent thrombus aspiration and stent-based primary PCI for STEMI between the years 2009 and 2013. Revascularization success was achieved in 83 patients with STEMI. These patients were divided into two groups according to BMI as normal weight (BMI < 25) or overweight (BMI > 25). At least 50% resolution of ST-segment up to 90 minutes after the procedure was defined as electrocardiographic good flow. Results: Among the 83 patients, 80% were overweight. While good flow observed in 79% of the patients, electrocardiographic perfusion success rates were similar in both groups. Overweight patients had better Killip class and higher initial left ventricular ejection fraction than normal weight patients. Angiographic characteristics were similar between the two groups except for the stent diameter which was higher in normal weight patients(Table 1). The usage of Glycoprotein IIb-IIIa antagonists was similar between the groups. In hospital and 30 day period, major adverse cardiac events (MACE) were not significantly different among the BMI categories.Conclusions: In the study, we demonstrated that despite similar myocardial reperfusion, patients with normal BMI had lower initial left ventricular ejection fraction and worse Killip class. The better results in overweight patients might indicate the presence of the phenomenon “obesity paradox” in patients who underwent thrombus aspiration in stent-based primary PCI for STEMI.

Absence of obesity paradox in Saudi patients admitted with acute coronary syndromes: insights from SPACE registry.

BACKGROUND AND OBJECTIVESTo describe the distribution of body mass index (BMI) and its relationship with clinical features, management, and in-hospital outcomes of patients admitted with acute coronary syndromes (ACS).DESIGN AND SETTINGSThe Saudi Project for Assessment of Coronary Events is a prospective registry. ACS patients admitted to 17 hospitals from December 2005–2007 were included in this study.METHODSBMI was available for 3469 patients (68.6%) admitted with ACS and categorized into 4 groups: normal weight, overweight, obese, and morbidly obese.RESULTSOf patients admitted with ACS, 72% were either overweight or obese. A high prevalence of diabetes (57%), hypertension (56.6%), dyslipidemia (42%), and smoking (32.4%) was reported. Increasing BMI was significantly associated with diabetes, hypertension, and hyperlipidemia. Overweight and obese patients were significantly younger than the normal-weight group (P=.006). However, normal-weight patients were more likely to be smokers and had 3-vessel coronary artery disease, worse left ventricular dysfunction, and ST elevation myocardial infarction. Glycoprotein IIb-IIIa antagonists were used significantly more in overweight, obese, and morbidly obese ACS patients than in normal-weight patients (P≤.001). Coronary angiography and percutaneous intervention were reported more in overweight and obese patients than in normal-weight patients (P≤.001). In-hospital outcomes were not significantly different among the BMI categories.CONCLUSIONHigh BMI is prevalent among Saudi patients with ACS. BMI was not an independent factor for in-hospital outcomes. In contrast with previous reports, high BMI was not associated with improved outcomes, indicating the absence of obesity paradox observed in other studies.

Correlation of platelet number and mean platelet volume with enhanced clopidogrel response in acute coronary syndrome determined by impendance aggregometry

Objective: Responsiveness to clopidogrel is characterized by large variablity in platelet inhibition among patients. (1) Enhanced response to clopidogrel correlates with higher risk for bleeding. (2) We sought to evaluate correlation of platelet count and mean platelet volume (MPV) with enhanced clopidogrel response in patients with acute coronary syndrome undergoing PCI. Methods: Two hundred and forty six consecutive patients with acute coronary syndromes (ACS) were included in the study. Patients with thrombocytopenia and those who received glycoprotein IIbIIIa antagonists during and after PCI were excluded (86 patients).

Suboptimal platelet response to clopidogrel after percutaneous coronary intervention in patients with acute coronary syndrome is not associated with total platelet count and mean platelet volume

Cardiologia CROATICA Objectives: Responsiveness to clopidogrel is characterized by large variability in platelet inhibition among patients. Suboptimal response to clopidogrel is known to be associated with higher risk for subsequent cardiovascular ischaemic events such as in-stent thrombosis or recurrent acute coronary syndrome (ACS). We sought to evaluate correlation of platelet count and mean platelet volume (MPV) with low clopidogrel response in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Patients and Methods: We enrolled 359 consecutive ACS patients in the study. Patients with thrombocytopenia, suboptimal PCI and those who received glycoprotein IIbIIIa antagonists during and/or after PCI were excluded (120 patients). Residual platelet activity specific to clopidogrel was measured using Multiplate function analyzer — a point of care instrument which determines platelet function in small quantities of whole blood. Results: Fifty-three patients (22.2%) had suboptimal response to clopidogrel. Average platelet number and MPV in patients with decreased response was 240.8x10/L (SD ± 52.40) and 9.63 fL (SD ± 1.00), respectively. Patients with normal or increased response had average platelet number of 226.6x10/L (SD ± 53.02) and average MPV 9.3 fL (SD ± 0,91). There was no statistically significant difference in total platelet number (P=0.07) nor MPV values (P=0.13) between low responders and other patients. Conclusion: MPV and total platelet number are not associated with low respond to clopidogrel after successful PCI in ACS.

The bivalirudin paradox

A series of trials have shown that bivalirudin, a direct thrombin inhibitor that does not require the cofactor antithrombin III to be effective, is a reasonable alternative to unfractionated heparin (UFH) alone or associated with glycoprotein IIb/IIIa antagonists (GPI) in patients undergoing percutaneous coronary interventions (PCI). Particularly in patients with acute coronary syndromes (ACS), the effects of bivalirudin are striking. In the HORIZONS-AMI trial, patients with persistent ST-segment elevation (STEMI) had lower 30-day rates of net adverse clinical events and major bleeding, largely due to the significantly lower 30-day rate of non-coronary artery bypass grafting major bleeding. Bivalirudin also resulted in significantly lower rates of all-cause mortality and cardiac mortality, a benefit that extended up to 3-year follow-up. The beneficial effects of bivalirudin as compared to UFH associated with abciximab were also observed in 1721 non-ST elevation myocardial infarction (NSTEMI) patients undergoing PCI in the ISAR REACT 4 study. Although no difference was found between the two treatment strategies in the 30-day primary endpoint, bivalirudin use resulted in a lower rate of major bleeding. Despite the abundant evidence of benefit provided by bivalirudin in the treatment of ACS and the high level of recommendation received by the most recent Guidelines, its use is still low. The reasons for this underuse are multifactorial, the most likely being the preference of operators for the use of a low-cost agent, like UFH, that can be associated with a GPI. Countering platelet hyperreactivity is still the main goal of interventional cardiologists treating ACS patients invasively, apparently downplaying the pathogenetic role of thrombin in this clinical condition.

Elevating local concentrations of GPIIb–IIIa antagonists counteracts platelet thrombus stability

Glycoprotein IIb–IIIa (GPIIb–IIIa) antagonists have the capacity to destabilize coronary thrombi and restore vessel patency. Antagonist concentration and residence time, which can be increased by local intracoronary (LIC) administration, and thrombus age may be key factors that influence thrombus stability. Light transmission aggregometry was used to examine the effects of exposing human platelet aggregates to extremely high local levels of GPIIb–IIIa antagonists versus conventional therapeutic levels in vitro. Freshly-formed or aged platelet aggregates were subjected to GPIIb–IIIa antagonists (abciximab, eptifibatide) or direct thrombin inhibitor bivalirudin at concentrations simulating either conventional intravenous (IV) or LIC administration. The degree of antagonist-induced disaggregation was significantly higher using elevated (LIC) doses versus conventional (IV) doses (60.1 % vs. 7.4 % for abciximab, 41.6 % or 45.3 % vs. 17.6 % for eptifibatide, p < 0.01). Bivalirudin did not promote disaggregation. Microscopy confirmed noticeably smaller, more dispersed aggregates for antagonist LIC treatments. Dosing at LIC levels also induced more disaggregation than IV levels when aggregates were aged for 30 min prior to exposure. An in vitro perfusion model was used to simulate the fluid dynamics of IV or LIC administration of abciximab using a microporous local drug delivery balloon catheter such as the Atrium ClearWay™ RX. The perfusion model resulted in more rapid thrombus clearance with LIC dosing levels compared to IV. In summary, boosting the concentration of GPIIb–IIIa antagonists enhances dispersal of human platelet aggregates in vitro. These data provide a foundation for investigating increased local concentrations of GPIIb–IIIa antagonists in patients, as with LIC administration.

Current Issues with Glycoprotein IIb-IIIa Antagonists

The development of glycoprotein (GP) IIb-IIIa antagonists is reviewed with particular emphasis on the characteristics of each agent, the pharmacodynamic profile of each agent, results in pivotal clinical trials, and the associated implications. GP IIb-IIIa antagonists have greatest benefit when used as adjunctive therapy during percutaneous coronary intervention (PCI) when the patient has intra-coronary thrombosis. These agents appear to provide greatest benefit when used in combination with heparin. The clinical niche for parenteral GP IIb-IIIa antagonists is evolving but appears to be for patients in transition, such as individuals requiring emergent PCI before oral agents are fully active and for unstable patients requiring transport to PCI centers. Subsequent studies should evaluate the optimal duration of therapy with GP IIb-IIIa antagonists.

Anti‐platelet therapy: glycoprotein IIb‐IIIa antagonists

Glycoprotein (GP) IIb-IIIa antagonists inhibit the aggregation of activated platelets. Three agents are approved for clinical use. In this review, the characteristics of each agent, their pharmacodynamic profile, results in pivotal clinical trials and the associated clinical implications are discussed. GP IIb-IIIa antagonists have greatest benefit when used as adjunctive therapy during percutaneous coronary intervention (PCI) when the patient has intra-coronary thrombosis. These agents appear to provide greatest benefit when used in combination with heparin. The clinical niche for parenteral GP IIb-IIIa antagonists is evolving. The rapid onset and offset of GP IIb-IIIa antagonists plus dosing designed to inhibit extensively platelet aggregation differentiates them from oral agents. The contemporary niche appears to include patients in transition, such as individuals requiring emergent PCI before oral agents are fully active and for unstable patients requiring transport to PCI centres, particularly in patients likely to have intracoronary thrombus. Subsequent studies should evaluate the optimal duration of therapy with GP IIb-IIIa antagonists.

Perioperatives Management der antithrombotischen Behandlung bei Stent-Patienten

Perioperative management of antiplatelet treatment in patients with coronary stents remains challenging as premature discontinuation may cause thrombotic events. To date, there is a lack of evidence-based results and guidelines to recommend adequate antithrombotic drug therapy in patients at high risk of stent thrombosis who undergo noncardiac surgery. According to our clinical experience with these patients, we propose a perioperative bridging of discontinued dual antiplatelet therapy by the „off-label“ use of low molecular weight glycoprotein IIbIIIa antagonist for up to 24 hours. Patients should be monitored by a perioperative point-of-care-testing and, thus, could benefit from the individually adapted antiplatelet therapeutic issue.

Delivery of Glycoprotein IIb/IIIa Inhibitor Therapy for Percutaneous Coronary Intervention

A major goal of any antithrombotic regimen administered during percutaneous coronary intervention (PCI) is the preservation of coronary microvascular perfusion, which is critical for myocardial survival. In addition to macrovascular thrombosis, microembolization into the downstream coronary artery bed that occurs during spontaneous plaque rupture and PCI plays a prominent role in the development of microvascular dysfunction that leads to myocardial infarction. In addition to physical obstruction of the lumen by the embolus, vasoconstriction and edema due to inflammation also impair microvascular flow.1 These events likely occur more frequently during PCI performed in the setting of unstable coronary syndromes.2 With Doppler guidewire technology, it was estimated that an average of 25 embolic events occurred during primary PCI for ST-segment elevation myocardial infarction.3 Article see p 784 Platelet aggregates are important components of coronary microemboli, along with leukocytes, erythrocytes, platelet-leukocyte aggregates, cholesterol crystals, and hyalin. Platelets and leukocytes within microemboli play a particularly important role in the pathophysiological changes of blood flow by promoting in situ microvascular thrombosis, vasoconstriction, and inflammation. Interestingly, the composition of the embolized material is similar in the settings of spontaneous and catheter-induced plaque rupture.1 In animal models, distal microembolization of inert microspheres is associated with an immediate reduction in flow due to vessel occlusion, followed by enhanced blood flow due to the effects of adenosine released from the embolized myocardium into the adjacent noninvolved myocardium.4 Microembolization results in overall reduced flow reserve and the progressive loss of contractile function, which often reverses within weeks. The degree of myocardial contractile dysfunction is disproportionate to the degree of infarction and is the result of inflammation.5 However, in the clinical condition, a more complex pathophysiology exists due to the influence of multiple components of the emboli. Platelets aggregate when fibrinogen binds to the active …

038 Glycoprotein IIbIIIa Inhibitors Improve Clinical Outcome after Coronary Stenting in Clopidogrel non Responders: a Prospective, Randomized Study

Numerous biological studies have reported inter-individual variability in platelet response to clopidogrel with clinical relevance. High Post treatment platelet reactivity (ADP-induced aggregation >70%) has been proposed to define Non response to clopidogrel. We assessed in clopidogrel non responders undergoing elective percutaneous coronary intervention (PCI) the benefit of adjusted antiplatelet therapy with glycoprotein IIbIIIa (GPIIbIIIa) antagonist administration during PCI for one month clinical outcome. 149 clopidogrel non-responders referred for elective PCI were prospectively included and randomized to “conventional group” (n=75) or “active group” with GPIIbIIIa antagonist (n=74). All patients received 250 mg aspirin and 600 mg clopidogrel before PCI and platelet testing. The rate of CV events at one month was significantly lower in the “active group” than in the “conventional group”: 19% (n=14) vs. 40% (n=30), p=0.006, [OR (95%CI): 2.8(1.4-6.0)]. No patient in either group had post procedural TIMI major bleeding or required transfusions. The present study suggested benefit of tailored antiplatelet therapy during elective PCI with GPIIbIIIa antagonist for clopidogrel non responders without increased bleeding risk.