Glycoprotein IIb/IIIa Inhibitors Use Research Articles

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.

Anticoagulant Therapy for Percutaneous Coronary Intervention

Received June 2, 2009; accepted November 16, 2009. Percutaneous coronary intervention (PCI) is the most commonly performed invasive therapeutic cardiac procedure and plays an important role in the treatment of ischemic heart disease. Since the first description of coronary angioplasty in a human by Gruntzig,1 the technique, equipment, and associated pharmacotherapy have undergone substantial evolution, leading to significant improvements in periprocedural complications.2 In particular, procedural anticoagulant therapy has been the focus of numerous clinical trials, and several options are now available and supported by practice guidelines; each agent has both advantages and disadvantages, and procedural pharmacotherapy continues to be a focus of drug development. The purpose of this review is to summarize the goals of anticoagulant therapy during PCI, the pharmacokinetics and pharmacodynamics of available agents, and the clinical data surrounding each agent and to identify new agents in development. The goals of pharmacotherapy during PCI are 2-fold: (1) to mitigate the sequelae of iatrogenic plaque rupture from balloon angioplasty or stenting and (2) to reduce the risk of thrombus formation on intravascular PCI equipment. Central to these thrombotic events is thrombin (factor IIa). Iatrogenic damage to the endothelium during PCI leads to increased expression of tissue factor, activation of the coagulation cascade, and formation of activated factor Xa. This ultimately leads to the generation of thrombin, conversion of fibrinogen to fibrin, and thrombus formation.3 In addition to its effects on fibrin, thrombin also directly activates platelets, enhances platelet aggregation, and is proinflammatory.4 Because of its multiple actions in promoting thrombosis, the focus of most anticoagulant agents is thrombin inhibition. Available agents for use include unfractionated heparin (UFH), low-molecular-weight heparins (LMWH, of which enoxaparin has the largest body of clinical data), the synthetic pentasaccharides (of which fondaparinux has the largest body of clinical data), and the …

Drug-eluting stents and glycoprotein IIb/IIIa inhibitors in vessels at low anatomic risk: A retrospective analysis of previously published data from the Basel Stent Kosten Effektivitäts Trial

Background: Drug-eluting stents (DESs) are associated with late stent thromboses, but the exact mechanism of action is unknown. Objective: The goal of this article was to assess the clinical interaction of glycoprotein IIb/IIIa inhibitors (GPIs) with different stent and vessel types in unselected patients undergoing percutaneous coronary intervention (PCI). Methods: This was a predefined retrospective analysis of the randomized controlled Basel Stent Kosten Effektivitats Trial (BASKET), which compared DES with bare-metal stents (BMSs) in patients undergoing PCI. Patients were compared for major adverse clinical events in relation to GPI use (abciximab and tirofiban) after 18 months. In a subgroup analysis prespecified in the study protocol, specific regard was given to angiographic groups at different risk levels for late events (high-risk vessels [ie, small vessels with a diameter <3.0 mm and saphenous vein grafts], and low-risk vessels [ie, large native vessels ≥3.0 mm]). Baseline differences between patients with or without GPI use were identified and incorporated into a multivariable Cox proportional hazards regression analysis if different at a <0.05 level. Results: A total of 826 patients (650 males, 176 females) were enrolled in BASKET; 301 (36%) received GPI therapy. Of these 301 patients, 255 (85%) received abciximab and 46 (15%) received tirofiban. After 18 months, the rate of cardiac death and nonfatal myocardial infarction was higher in patients with GPI use than in those without GPI use (35/301 [12%] vs 32/525 [6%]; P = 0.005). In patients undergoing PCI in anatomically low-risk vessels and receiving GPI therapy, there was a higher rate of cardiac death and nonfatal myocardial infarction at 18 months with a DES versus a BMS (22/151 [15%] vs 3/66 [5%]; P = 0.033). In patients undergoing PCI in anatomically low-risk vessels and without GPI therapy, there was no significant difference for cardiac death and nonfatal myocardial infarction (DES vs BMS, 11/207 [5%] vs 6/134 [4%]). In the multivariable analysis, GPI use (hazard ratio = 2.93; 95% CI, 1.53-5.63; P = 0.001) and age (hazard ratio = 1.034 per year increase; 95% CI, 1.008-1.062; P = 0.012) remained the only significant independent predictors of outcome. Interaction of stent type and GPI use was significant ( P = 0.006). Conclusions: This retrospective analysis of the BASKET data found that GPIs and DESs used in patients with large native vessels may have an adverse interaction in terms of late stent thromboses. However, large prospective studies are needed to confirm these findings.

Effectiveness of the transradial approach to reduce bleedings in patients undergoing urgent coronary angioplasty with GPIIb/IIIa inhibitors for acute coronary syndromes

To analyze the effectiveness of the transradial approach in reducing bleeding rates following urgent percutaneous coronary intervention (PCI) in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors (GPIs). PCI and use of GPIs are recommended in acute coronary syndromes, but are strong predictors of severe hemorrhagic complications, which, in turn, are associated with reduced survival. The transradial approach represents a simple and effective solution to reduce vascular access site bleedings, particularly with GPIs. All consecutive patients undergoing urgent transradial PCI under GPI treatment were enrolled in the registry. No patients were excluded. In addition, we performed a case-matched comparison of the transradial versus transfemoral approach using propensity analysis to adjust for known risk factors for bleeding. The primary end point was the rate of bleedings, graded according to the Thrombolysis in Myocardial Infarction (TIMI) classification. Five hundred thirty-one consecutive patients were prospectively enrolled in the registry. TIMI major, minor, and minimal bleedings were 0.2%, 1.7%, and 6.4%, respectively. Transfusion rate was 0.8%. After propensity-matched analysis, the transradial approach was associated with significantly lower rates of all types of bleedings, while the transfemoral approach was the strongest predictor of TIMI major/minor bleedings (odds ratio 6.67; 95% confidence interval 1.72-25; P = 0.006). The transradial approach dramatically reduces access site bleedings, including TIMI major and minor bleedings, and transfusion rate, while preserving procedural success and clinical outcome. The transradial approach is an attractive solution to reduce bleeding complications in patients treated with GPIs.

Guidelines to Practice Gap in the Use of Glycoprotein IIb/IIIa Inhibitors: From ISAR‐REACT to Overreact?

Adjunctive use of glycoprotein IIb/IIIa inhibitors (GPI) is associated with favorable outcomes following percutaneous coronary intervention (PCI). Guidelines for use of GPI have been published by various national societies including National Institute of Clinical Excellence (NICE), United Kingdom. The latter has not been updated since publication. The impact of contemporary trials such as ISAR-REACT (which showed no benefit of abciximab and 600 mg of clopidogrel compared with 600 mg of clopidogrel alone, in elective patients) on adherence to NICE guidelines is unknown. We audited use of GPI against NICE guidelines following publication in May 2002. Data were collected from 1,685 patients between September and November in years 2002, 2003, 2004, and 2007. In 2002 and 2003, only 10.2% and 11.8%, respectively, of patients were noncompliant to NICE guidelines. Over time, there was an increase in patients not given GPI despite meeting NICE criteria. After publication of ISAR-REACT, the comparative figures for noncompliance in 2004 and 2007 were 40.0% and 44.5%. A similar pattern was seen in patients with diabetes; in 2002 and 2003 noncompliance was 16.7% and 11.1%, respectively, and in 2004 and 2007 noncompliance was 38.0% and 44.7%, respectively. Qualitatively, similar findings were recorded in patients with NSTE-ACS. The overall noncompliance to NICE guidelines increased from 11.0% to 42.1% (P < 0.0001) after the ISAR-REACT study. We found a decline in compliance to NICE guidelines on GPI usage during PCI. This was likely influenced by contemporary trials demonstrating little or no benefit of GPI in patients undergoing elective PCI who are adequately pretreated with clopidogrel. Our findings suggest the need for a mechanism whereby regular updates to guidelines can be disseminated following new trial evidence.

Percutaneous coronary interventions in octogenarians: Acute and 12 month results in a large single‐centre experience

To review the results of PCI in patients aged >or=80 years. Octogenarians represent a growing proportion of patients treated with PCI; in this subset of high-risk patients, the role of complete revascularization is still controversial. We examined in-hospital, 30 days, and 12-month events in 356 patients aged >or=80 years submitted to PCI from 2004 to 2006 and 754 patients aged <80 years treated in 2006. Octogenarians had a higher risk profile. A complete revascularization was obtained in 48% of them and in 65% of younger patients (P < 0.001); glycoprotein IIb/IIIa inhibitors (GPI) use was common in both groups (43 vs. 46.5%). In-hospital mortality was higher in octogenarians (3.9 vs. 1.3%, P = 0.01) as well as vascular complications (2.8 vs. 1%, P = 0.058). Mortality resulted 5.9 vs. 1.2% at 30 days (P < 0.001), and 16.3 vs. 3.9% at 12 months (P <0.001) in the two groups whereas repeat revascularization procedures did not differ (9.3 vs. 8.4%, respectively). In patients aged >or=80, there was no difference in 12 months total events (20 vs. 28%, P = 0.07) and repeat revascularizations (8 vs. 10%, P = 0.498) in completely or uncompletely revascularized subjects. At multivariate analysis age (P = 0.002), diabetes (P = 0.002), three vessel disease (P = 0.020) and procedural success (P = 0.002) were independent predictors of total events at 12 months. In our experience, frequent GPI use and multivessel PCI in 41% of >or=80 years-old patients resulted in good immediate and mid-term clinical outcomes, irrespective of the completeness of revascularization achieved.

Are glycoprotein inhibitors safe during percutaneous coronary intervention in patients on chronic warfarin treatment?

The aim of this study was to evaluate the safety of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI) in patients on chronic warfarin therapy due to atrial fibrillation (AF). We analysed all consecutive AF patients (N = 377, mean age 70 years, male 71%) on warfarin therapy referred for PCI in seven centres. Major bleeding, access site complications and major adverse cardiovascular events were recorded during hospitalisation. A total of 111 patients (29%) received periprocedural GPIs with a wide inter-hospital variation in their use (range 3-68%). The use of GPIs increased with the severity of the disease presentation and 49% of patients with ST-elevation myocardial infarction received GPIs. Mean periprocedural international normalised ratio (INR) of patients who received GPIs was 1.89 (range 1.1-3.3). Major bleeding was more common in the patients treated with GPIs (9.0% vs. 1.5%, p = 0.001) than in those without GPIs, but there was no difference in major adverse cardiovascular events between the groups. In multivariable analysis, use of GPIs (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.3-20.6, p = 0.02) and old age (OR 1.2, 95% CI 1.0-1.3, p= 0.02) remained as the only independent predictors of major bleeding. Also after adjusting for propensity score, GPIs remained as a significant predictor of major bleeding (OR 3.8, 95% CI 1.03-14.1, p = 0.045). In the GPI group, major bleeding was not predicted by INR level or warfarin pause. GPIs increase the risk of major bleeding events irrespective of periprocedural INR levels and should be used with caution in this fragile patient group.

Femoral pseudoaneurysms and current cardiac catheterization: Evaluation of risk factors and treatment

Objectives We sought to determine the incidence of femoral pseudoaneurysm (FPA) following cardiac catheterization, identify the risk factors for FPA and factors influencing therapeutic strategy. Methods 11,992 consecutive patients who underwent cardiac catheterization via femoral artery were studied over a period of four years in one University Hospital. Our prospective case control group analysis registered patients who developed FPA after the procedure. Patient-related factors, procedure related factors and peri-procedure treatment were compared between the two groups. Results 76 FPA were diagnosed over the study period accounting for a global incidence of 0.6% procedures. By univariate analysis, interventional procedure ( p < 0.01), rhythmologic procedure ( p = 0.03), sheath ≥ 6F ( p = 0.04) and left groin puncture ( p < 0.001) were FPA risk factors. By multivariate analysis, interventional procedure (adjusted odds ratio [OR] = 1.99; 95% confidence interval [CI]1.14–3.44 p = 0.01) and left groin puncture (OR = 4.65; 95% CI, 1.78–12.1 p = 0.001) are independent predictive factors of FPA. FPA thrombosis was obtained by ultrasound guided compression (UGC) in 71% of the cases. By univariate analysis, PFA diameter larger than 4 cm ( p < 0.001), the use of anticoagulation ( p < 0.01) or GPIIbIIIa inhibitors ( p = 0.001) and UGC under anticoagulation ( p = 0.01) are predictive factors of need for FPA surgical repair. By multivariate analysis, FPA diameter > 4 cm and use of GPIIbIIIa inhibitors are independent predictive factors of FPA's surgical treatment. Superficial femoral puncture was predictive of successful UGC both by uni and multivariate analysis. Conclusions Our study shows that FPA occurrence is mainly due to by procedure-related factors. FPA size, level of puncture and the use of GPIIbIIIa inhibitors are independent predictive factors of need for surgical therapy.

Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use

Clopidogrel pretreatment before percutaneous coronary intervention (PCI) has been shown to reduce the risk of death and ischemic complications after PCI. However, the need for clopidogrel pretreatment is debated in patients receiving a glycoprotein IIb/IIIa inhibitor (GPI). We performed a collaborative meta-analysis of the results of 3 randomized trials of clopidogrel pretreatment: PCI-CURE, CREDO, and PCI-CLARITY. Patients were stratified based on GPI use at the time of PCI (a postrandomization subgroup analysis). Odds ratios (ORs) and 95% CIs for the effect of clopidogrel pretreatment versus placebo pretreatment on the incidence of cardiovascular death, myocardial infarction (MI), or stroke for up to 30 days after PCI were calculated for each trial within each GPI stratum and were combined using a random effects model. Six thousand three hundred twenty-five patients were included, 32.4% of whom received a GPI. There was a consistent benefit of clopidogrel pretreatment in reducing the incidence of cardiovascular death, MI, or stroke after PCI both in patients who did not receive a GPI (OR 0.72, 95% CI 0.53-0.98, P = .03) and in those who did (OR 0.69, 95% CI 0.47-1.00, P = .05). There was no evidence of heterogeneity in the benefit of clopidogrel pretreatment between GPI use strata (P = .85 for heterogeneity). Clopidogrel pretreatment was not associated with a significant excess of TIMI major or minor bleeding, either in those who did not receive a GPI (OR 1.20, 95% CI 0.76-1.92) or in those who did (OR 1.22, 95% CI 0.71-2.09) (P = .97 for heterogeneity). Clopidogrel pretreatment before PCI is beneficial and safe regardless of whether a GPI is used at the time of PCI.

Platelet glycoprotein IIb/IIIa inhibitors in acute ischemic stroke

Acute ischemic stroke (AIS) is a common cause of morbidity and mortality worldwide. Thrombolytic therapy with tissue plasminogen activator, the only approved treatment for AIS, is received by less than 2% of patients. Moreover, there is a slight increase in hemorrhagic complications with thrombolysis. Therefore, there is a need for newer therapeutic modalities in AIS, which could be used in window periods beyond 3-6 h after stroke onset with fewer hemorrhagic complications. Glycoprotein IIb/IIIa inhibitors (GPI), after their initial success in patients with acute coronary syndromes, promised much in patients with AIS over the past decade or so. However, their exact role in patients with AIS, including the window periods and type of strokes, and the risk of symptomatic or asymptomatic hemorrhage are unclear at the moment. The current review focuses on the literature concerning the use of GPI in AIS and looks at the available evidence regarding their use. Abciximab thought to be safe and effective in initial case series and early trials, has not been shown to improve outcomes in AIS, and is associated with higher rates of hemorrhage. Tirofiban appears to be safe and effective in initial trials and there is a need to conduct further trials to establish its role in AIS.

Predictors and Impact of Major Hemorrhage on Mortality Following Percutaneous Coronary Intervention from the REPLACE-2 Trial

Patients undergoing percutaneous coronary intervention (PCI) have a significant risk of hemorrhagic complications. Predictors of major hemorrhage and its relation to mortality in PCI are not well defined. Baseline and periprocedural predictors of major hemorrhage and its impact on mortality in patients undergoing elective or urgent PCI randomly assigned to heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin plus provisional GPIs in the REPLACE-2 Trial were determined. Of 6,001 patients, 3.2% experienced a major hemorrhage. Independent baseline predictors of major hemorrhage included advanced age, female gender, impaired creatinine clearance, and anemia. Independent periprocedural predictors of major hemorrhage included treatment with heparin plus GPI, increased procedural duration, provisional use of GPI, increased time to sheath removal, length of intensive care unit stay, and use of an intra-aortic balloon pump (all p <0.05). Mortality rates were higher in patients with than without major hemorrhage at 30 days (5.1% vs 0.2%), 6 months (6.7% vs 1.0%), and 1 year (8.7% vs 1.9%; p <0.001 for all). Furthermore, major hemorrhage was an independent predictor of 1-year mortality (odds ratio 2.66, 95% confidence interval 1.44 to 4.92, p = 0.002). In conclusion, in patients undergoing elective or urgent PCI, major hemorrhage was an independent predictor of 1-year mortality. A number of baseline and periprocedural factors independently predicted major hemorrhage, including treatment with heparin plus GPI.

Comparison of Patient Outcomes with Bivalirudin versus Unfractionated Heparin in Percutaneous Coronary Intervention

To compare clinical outcomes and glycoprotein IIb-IIIa inhibitor use in patients undergoing percutaneous coronary intervention (PCI) who received bivalirudin or unfractionated heparin (UFH) in a real-world setting. Retrospective cohort analysis. University-affiliated medical center. One thousand seventy-five adult patients who underwent PCI and received either bivalirudin (539 patients) or UFH (536 patients) from April 1, 2003-April 1, 2004. Patient data on demographics, comorbidities, laboratory values, and reports of radiologic examinations, cardiac catheterizations, and discharge summaries were obtained. Outcomes evaluated included rates of in-hospital mortality, myocardial infarction, revascularization, and length of stay (LOS), as well as Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) and Thrombosis in Myocardial Infarction (TIMI) bleeding categorization. Bivalirudin use was associated with a significant reduction in TIMI major (5.0% vs 9.7%, p=0.003), REPLACE-2 major (5.4% vs 12.9%, p<0.001), and TIMI minor (1.7% vs 6%, p<0.001) bleeding complications compared with UFH use. Significantly fewer patients in the bivalirudin group received glycoprotein IIb-IIIa inhibitors (27.3% vs 62.7%, p<0.001). Patients receiving bivalirudin had significantly fewer myocardial infarctions after catheterization (10.7% [40/375] vs 18.0% [51/284], p=0.007). No differences were noted in mortality and revascularization rates between groups. A shortened LOS was observed in the bivalirudin group. This real-world analysis that included high-risk patients provides further evidence that bivalirudin is an attractive alternative to UFH because of a decrease in bleeding events without compromising efficacy.

The efficacy and safety of combination glycoprotein IIbIIIa inhibitors and reduced-dose thrombolytic therapy–facilitated percutaneous coronary intervention for ST-elevation myocardial infarction: A meta-analysis of randomized clinical trials

We reviewed the literature and performed a meta-analysis comparing the safety and efficacy of adjunctive use of reduced-dose thrombolytics and glycoprotein (Gp) IIbIIIa inhibitors to the sole use of Gp IIbIIIa inhibitors before percutaneous coronary intervention (PCI) in patients presenting with acute ST-segment elevation myocardial infarction (STEMI). Early reperfusion in STEMI is associated with improved outcomes. The use of reduced-dose thrombolytic and Gp IIbIIIa inhibitors combination before PCI in the setting of acute STEMI remains controversial. We performed a literature search and identified randomized trials comparing the use of combination therapy-facilitated PCI versus PCI done with Gp IIbIIIa inhibitor alone. Included studies were reviewed to determine Thrombolysis in Myocardial Infarction (TIMI)-3 flow at baseline, major bleeding, 30-day mortality, TIMI-3 flow after PCI, and 30-day reinfarction. We performed a random-effect model meta-analysis. We quantified heterogeneity between studies with I2. A value >50% represents substantial heterogeneity. We identified 4 clinical trials randomizing 725 patients; 424 patients were pretreated with combination therapy before PCI, and 301 patients had Gp IIbIIIa inhibitor alone during PCI. Combination therapy-facilitated PCI was associated with a 2-fold increase in TIMI-3 flow upon arrival to the catheterization laboratory compared with the sole use of upstream Gp IIbIIIa inhibitors (192/390 patients [49%] versus 60/284 [21%]; relative risk [RR], 2.2; P < .00001). However, post-PCI TIMI-3 flow was similar between the 2 groups (279/319 patients [87%] versus 188/212 [88%]; RR, 0.99; P = .85). Major bleeding events significantly increased in the combination therapy group (40/420 patients [9.5%] versus 14/299 [4.7%]; RR, 2.2; P = .007). The 30-day mortality (15/424 patients [3.5%] versus 5/301 [1.7%]; RR, 1.47; P = .46) and 30-day reinfarction rate (5/424 patients [1.1%] versus 3/301 [1.0%]; RR, 0.96; P = .96) were similar in the 2 treatment groups. Awaiting the results of the ongoing clinical trials, the current cumulative evidence does not support the routine use of combination of reduced-dose thrombolytic and Gp IIbIIIa inhibitor therapy-facilitated PCI for the treatment of STEMI.

Debate of Adjunctive Pharmacology for Percutaneous Coronary Intervention: Thrombin Inhibitors and Clopidogrel Are Enough

The role of adjunctive pharmacology for percutaneous coronary intervention (PCI) has been extensively studied, but controversy remains regarding the optimal regimen. While older studies suggest that glycoprotein IIb/IIIa inhibitors (GPI) should be routinely administered, much of this evidence was collected prior to the era of widespread stenting and thienopyridine use. There is now substantial clinical evidence that bivalirudin monotherapy is the optimal adjunctive pharmacology for the vast majority of patients undergoing elective or urgent percutaneous coronary intervention (PCI), including those presenting with an acute coronary syndrome (ACS). Bivalirudin monotherapy provides similar protection from ischemic complications with a reduced rate of major hemorrhage, resulting in a superior net clinical outcome compared with the use of GPI.

Anticoagulant and antiplatelet medications

In the article, “Non–ST-Segment Elevation Acute Coronary Syndromes: Management Strategies for Optimal Outcomes” (February 2006[suppl]: S8-S34), Susan Housholder-Hughes presents a very good, broad overview of many facets of this syndrome and its management. However, there is some information on anticoagulant and antiplatelet medications that I feel may be misleading and benefit from further clarification.On page 23, it is stated that direct thrombin inhibitors do not require monitoring; however, they do. Argatroban, lepirudin, and hirudin all must be closely monitored by partial thromboplastin time (PTT) as often as every 2 hours to ensure appropriate dosing. With argatroban, PTT should be checked 2 hours after initiation of the infusion, and 2 hours after any change, then can be decreased to twice daily if at goal range. For lepirudin and hirudin, PTT should be checked 4 hours after initiation or change, then can be decreased to daily if at goal range. Also, because argatroban is cleared hepatically, the starting infusion rate should be lower than the 2.0 μg/kg/min noted if there is any hepatic impairment.Lepirudin and hirudin are cleared renally and dose adjustments are also necessary. Bivalirudin (more commonly used during percutaneous interventions) should have associated activated clotting time monitoring, if there is any renal impairment.The issue of thrombocytopenia resulting from use of some glycoprotein IIb-IIIa receptor inhibitors is reviewed; however, it is not noted that a baseline platelet count of under 100000 is a contraindication to using any of these agents. It is also stated (page 24) that eptifibitide “has not been associated with increased rates of thrombocytopenia vs placebo,” with reference given to the PURSUIT trial experience in 1999.1 While realizing that the article was written in 2004, a review of more recent references since 1999 would have been helpful to show how more recent clinical experiences have added to the side effect profile of the drug. Although thrombocytopenia appears to be less common with eptifibatide, there have been several reports of severe thrombocytopenia associated with eptifibatide,2–5 and myself and my colleagues have experienced this clinically many times as well.The comments about the need for monitoring of direct thrombin inhibitors and the contraindication to use of glycoprotein IIb-IIIa inhibitors in patients with a platelet count of less than 100000/mL are valid and accurate, and I thank Ms Chevoya for this clarification.As for the lack of increase in thrombocytopenia with eptifibatide versus placebo, the prescribing information for INTEGRILIN (eptifibatide) states that the rates of thrombocytopenia in the PURSUIT trial with eptifibatide and placebo were similar. As reported by McClure and colleagues,1the rates of thrombocytopenia (defined as platelet count<100000/mL or <50% of baseline) in the PURSUIT trial were 7% (319/4603) in the placebo group and 6.9% (314/4614) in the eptifibatide group, demonstrating that eptifibatide is not associated with increased incidence of thrombocytopenia versus placebo. Randomized, placebo-controlled clinical trials, such as PURSUIT, provide the most reliable scientific evidence regarding the prevalence of relatively infrequent events, such as thrombocytopenia, while also allowing the comparison of individual event rates with the active drug versus placebo. Although individual cases of severe thrombocytopenia in patients receiving eptifibatide have been reported in the literature, as noted by Ms Chevoya, it is unclear whether thrombocytopenia is directly related to the use of this drug in these cases. Additionally, these case reports do not have a control group, in contrast to randomized, placebo-controlled trials. Finally, treatment with eptifibatide, including readministration within 28 days, has not been associated with development of antibodies to eptifibatide (as described in the INTEGRILIN prescribing information), a finding that is consistent with the absence of increased thrombocytopenia with eptifibatide versus placebo in the PURSUIT trial. Therefore, in my opinion, the statement “eptifibatide has not been associated with increased rates of thrombocytopenia vs placebo” is still accurate and valid.

Does X-sizer thrombectomy abrogate the inferior outcomes in patients with impaired TIMI flow before mechanical reperfusion for acute myocardial infarction?

Patients undergoing primary mechanical reperfusion forST elevation myocardial infarction (STEMI) in whomnormal antegrade flow (thrombolysis in myocardial infarc-tion grade 3 [TIMI-3] flow) is present in the culpritepicardial vessel at diagnostic angiography have beenshown to be associated with better outcomes than thosewith impaired antegrade flow (TIMI-0–2) [1]. A recentprospective, randomized study suggests that pre-treatmentwith X-sizer thrombectomy before percutaneous coronaryintervention (PCI) in acute coronary syndrome can improvefinal epicardial flow and accelerate ST-segment recovery[2,3]. In this study, we sought to determine whether X-sizerthrombectomy could abrogate the inferior outcomes inpatients with STEMI in whom initial angiography showedTIMI-0–2 flow.Patients with STEMI who underwent primary mechan-ical reperfusion using X-sizer thrombectomy before PCIbetween November 2000 and February 2003 were analyzed.Patients were selected because of arteriographic evidence ofthrombus. Patients were divided into two groups dependingon whether the initial angiography showed normal (TIMI-3)or impaired (TIMI-0–2) flow.Among the 95 study patients, normal antegrade flow(TIMI-3) was present in 13% (n=12) at initial angiography.For the remaining patients with impaired TIMI flow, 83.1%(n=69) had TIMI-0, 12.1% (n=10) TIMI-1 and 4.8% (n=4)TIMI-2 flow. The demographic, risk factor and treatmentprofiles of the two groups were shown in Table 1. Comparedwith patients without TIMI-3 flow, those with TIMI-3 flowbefore thrombectomy had greater left ventricular ejectionfraction (52F12% versus 43F12%, p=0.05), trend towardslower incidence of cardiogenic shock (0% versus 8.4%,p=0.2) and use of glycoprotein IIbIIIa inhibitors (0% versus

The platelet in diabetes: focus on prevention of ischemic events.

Accelerated atherosclerosis and the increased risk of thrombotic vascular events in diabetes may result from dyslipidemia, endothelial dysfunction, platelet hyperreactivity, an impaired fibrinolytic balance, and abnormal blood flow. There is also a correlation between hyperglycemia and cardiovascular (CV) events. The importance of platelets in the atherothrombotic process has led to investigation of using antiplatelet agents to reduce CV risk. A meta-analysis conducted by the Antiplatelet Trialists' Collaboration demonstrated that aspirin reduced the risk of ischemic vascular events as a secondary prevention strategy in numerous high-risk groups, including patients with diabetes. Based on results from placebo-controlled randomized trials, the American Diabetes Association recommends low-dose enteric-coated aspirin as a primary prevention strategy for people with diabetes at high risk for CV events. Clopidogrel is recommended if aspirin allergy is present. There is occasionally a need for an alternative to aspirin or for additive antiplatelet therapy. Aspirin in low doses inhibits thromboxane production by platelets but has little to no effect on other sites of platelet reactivity. Agents such as ticlopidine and clopidogrel inhibit ADP-induced platelet activation, whereas the platelet glycoprotein (Gp) IIb/IIIa complex receptor antagonists block activity at the fibrinogen binding site on the platelet. These agents appear to be useful in acute coronary syndromes (ACSs) in diabetic and nondiabetic patients. A combination of clopidogrel plus aspirin was more effective than placebo plus standard therapy (including aspirin) in reducing a composite CV outcome in patients with unstable angina and non-ST segment elevation myocardial infarction. In a meta-analysis of six trials in diabetic patients with ACSs, intravenous GpIIb-IIIa inhibitors reduced 30-day mortality when compared with control subjects. Results from controlled prospective clinical trials justify the use of enteric-coated low-dose aspirin (81-325 mg) as a primary or secondary prevention strategy in adult diabetic individuals (aged >30 years) at high risk for CV events. Recent studies support the use of clopidogrel in addition to standard therapy, as well as the use of GpIIb-IIIa inhibitors in ACS patients.

Frequency of abrupt vessel closure and side branch occlusion after percutaneous coronary intervention in a 6.5-year period (1994 to 2000) at a single medical center

The aims of this study were to analyze the contemporary trends in the changing incidence of abrupt vessel closure (AVC) after percutaneous coronary intervention (PCI), to determine the impact of intracoronary stenting and glycoprotein IIb/IIIa inhibitors (GPIs) on complication rates and etiologies, and to determine the incidence of side branch occlusion (SBO) as the etiology of AVC in the stent era, complications occurring during 3,300 consecutive PCIs performed from April 1994 to December 2000 at a single referral institution. In this consecutive patient cohort of PCI cases collected over a 6.5-year period, AVC occurred in 103 of 3,300 cases (3.12%). Linear regression analysis over this time frame documented a steadily decreasing incidence of AVC from 5.9% in 1994 to 1.1% in 2000 (−0.76%/per year, 95% confidence interval −0.99 to 0.52, p <0.05). Analysis using Pearson’s correlation showed that the decreasing incidence of AVC was inversely correlated with the increasing percentage of intracoronary stents placed over this time period (r = −0.94, p <0.001). Additionally, GPI use increased from 0% in 1995 to 36.0% in 2000 (p = 0.009). The absolute incidence of SBO of a major branch vessel remained relatively stable over this 6.5-year period. However, SBO appeared to be increasing as the etiology of AVC, and accounted for 9.0% of AVC in 1995 compared with 28.0% of AVC in 2000. This increasing trend of the percentage of SBO as the etiology of AVC appeared to correlate with the increased use of stents (r = 0.85, p = 0.015). Thus, the incidence of AVC steadily decreased over the 6.5-year time period, and was associated with the increased use of stents and GPIs; conversely, SBO accounted for an increasing percentage of AVC over this time period.

A symposium: Safety issues concerning the use of glycoprotein IIb-IIIa inhibitors in the management of Acute Coronary Syndromes

A symposium: Safety issues concerning the use of glycoprotein IIb-IIIa inhibitors in the management of Acute Coronary Syndromes