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High-dose, single-bolus eptifibatide: A safe and cost-effective alternative to conventional glycoprotein IIb/IIIa inhibitor use for elective coronary interventions
Abstract
Adjunctive pharmacotherapy with eptifibatide, a glycoprotein (GP) IIb/IIIa inhibitor, as an intravenous bolus followed by infusion has been shown to improve outcomes in elective coronary interventions (PCI). However, bleeding complications and costs have limited the routine adoption of this regimen.
The goal of this study was to examine the safety, efficacy and cost-effectiveness of high-dose, single-bolus eptifibatide, without post-intervention infusion, in "real-world" patients undergoing elective PCI.
We studied 401 patients with stable and unstable angina who were treated with a high-dose (20 mg), single bolus of eptifibatide plus heparin prior to the start of elective PCI. Exclusion criteria included recent MI, stenting of bypass graft(s), rotational atherectomy and/or brachytherapy. The primary study endpoints were major adverse clinical events (MACE), defined as the in-hospital and 30-day incidence of death from any cause, Q-wave or non-Q-wave MI, repeat target vessel revascularization and/or major bleeding complications.
Relevant demographic and procedural characteristics included mean age: 66.4 +/- 11.2; male gender: 242/401 (61%); number of vessels treated per patient: 1.46 +/- 0.42; and number of stents deployed per patient: 1.82 +/- 0.65. In-hospital non-Q-wave MI (CPK and/or CPK-MB > 3 times the upper limit of normal) occurred in 7/401 patients (1.75%) and MACE was 2.25%. Major bleeding complications were seen in 2/401 patients (0.49%). There were 4 additional MACE events at 30-day follow up (total MACE and bleeding = 3.25%). The average anticoagulation cost was 66 dollars/patient.
Intravenous eptifibatide, administered as a high-dose (20 mg) single-vial bolus, is a safe, effective and highly cost-effective alternative to the conventional regimens of bolus plus prolonged intravenous GP IIb/IIIa inhibitor infusion for patients undergoing elective PCI.
... The effect measure was cases of atrial fibrillation avoided, and since this only occurs during admission, the authors chose to include only costs during admission. Thus, the authors ignored not only downstream health care costs but also the impact on survival and HRQoL of avoided atrial fibrillation during admission.The study byFischell et al (2006) focused on the use of Eptifibatide -a pharmaceutical that prevents complications following angioplasty138 . The authors chose a time frame of one month, thus disregarding downstream health care cost savings beyond one month, and potential QALY effects of avoided complications.Lewin et al (2009) analysed the cost-effectiveness of a rehabilitation scheme for patients receiving an ICD, and included physical and mental health as well as hospital admissions as effect measures118 . ...
... The effect measure was cases of atrial fibrillation avoided, and since this only occurs during admission, the authors chose to include only costs during admission. Thus, the authors ignored not only downstream health care costs but also the impact on survival and HRQoL of avoided atrial fibrillation during admission.The study byFischell et al (2006) focused on the use of Eptifibatide -a pharmaceutical that prevents complications following angioplasty138 . The authors chose a time frame of one month, thus disregarding downstream health care cost savings beyond one month, and potential QALY effects of avoided complications.Lewin et al (2009) analysed the cost-effectiveness of a rehabilitation scheme for patients receiving an ICD, and included physical and mental health as well as hospital admissions as effect measures118 . ...
... Because of these issues, some interventional cardiologists use a catheterization laboratory-only eptifibatide regimen and forego the infusion after successful stent implantation. 9,10 This practice has been growing in recent years although there are limited data on the clinical safety and efficacy of such an approach. Accordingly, we used advanced matching techniques to assess the efficacy and safety of this off-label regimen and compared it with the conventional bolus plus infusion regimen in a large cohort of patients undergoing contemporary PCI. ...
Eptifibatide, a small-molecule glycoprotein IIb/IIIa inhibitor, is conventionally administered as a bolus plus infusion. A growing number of clinicians are using a strategy of catheterization laboratory-only eptifibatide (an off-label use) as procedural pharmacotherapy for patients undergoing percutaneous coronary intervention although the comparative effectiveness of this approach is unknown.
We compared the in-hospital outcome of patients undergoing percutaneous coronary intervention across 47 hospitals and treated with eptifibatide bolus plus infusion with those treated with a catheterization laboratory-only regimen. We used optimal matching to link the use of catheterization laboratory-only eptifibatide with clinical outcomes, including mortality, myocardial infarction, bleeding, and need for transfusion. Of the 84 678 percutaneous coronary interventions performed during 2010 to 2011, and meeting our inclusion criteria, eptifibatide was administered to 21 296 patients. Of these, a catheterization laboratory-only regimen was used in 4511 patients, whereas 16 785 patients were treated with bolus plus infusion. In the optimally matched analysis, compared with bolus plus infusion, a catheterization laboratory-only regimen was associated with a reduction in bleeding (optimally matched adjusted odds ratio, 0.74; 95% confidence interval, 0.58-0.93; P=0.014) and need for transfusion (optimally matched adjusted odds ratio, 0.70; 95% confidence interval, 0.52-0.92; P=0.012), with no difference in mortality or myocardial infarction.
A catheterization laboratory-only eptifibatide regimen is commonly used in clinical practice and is associated with a significant reduction in bleeding complications in patients undergoing contemporary percutaneous coronary intervention.
© 2015 American Heart Association, Inc.
... Notwithstanding the weaker effect of LMWH against thrombosis induced by foreign objects compared with UFH [9,33], thrombosis within the sheath occurred in only one patient of the dalteparin group, which is not statistically different from that of the UFH group. Therefore, the choice of dalteparin does not mean that more thrombosis was induced by foreign objects. ...
Background
The aim of this study was to investigate the safety and efficacy of dalteparin during an elective percutaneous coronary intervention (PCI) procedure in a large cohort.
Materials and methods
In this prospective, randomized, open-label design study, 733 patients undergoing elective PCI were divided into an unfractionated heparin group (group 1, 323 patients) or a dalteparin group (group 2, 410 patients). Blood samples were collected before and 18–24 h after the PCI procedure to determine the serum levels of cardiac troponin I (cTnI) and creatine kinase isoenzyme MB. Major adverse cardiac events (MACEs) and bleeding events during hospitalization were also recorded. Patients with an increased level of serum cTnI before PCI were excluded from the study.
Results
After PCI, the cTnI values were greater than three times the upper limit of normal in 43 cases (13.3%) in group 1 and 52 cases (12.7%) in group 2, without a statistically significant difference between the two groups (P=0.801). An increased creatine kinase isoenzyme MB level of greater than two times the upper limit of normal was found in 10 cases (3.1%) in group 1 and 12 cases (2.9%) in group 2, without a statistically significant difference between the two groups (P=0.894). Postoperative bleeding was observed in nine patients (2.8%) in group 1 and six patients (1.5%) in group 2. Postoperative MACEs were observed in two patients (0.6%) in group 1 and two patients (0.5%) in group 2. There were no significant differences between the two groups with respect to bleeding events or MACEs.
Conclusion
Our study showed that dalteparin might be as effective and safe as unfractionated heparin for anticoagulation during elective PCI.
... The findings suggest that a bolus administration prior to or at the time of cardiac catheterization or PCI while eliminating the intraprocedural infusion of the GP IIb/IIIa antagonists may reduce bleeding complications. [44][45][46] Kini et al evaluated cardiac events, bleeding complications, and cost in patients undergoing PCI who received the GP IIb/IIIa bolus alone compared with patients who received GP IIb/ IIIa bolus in addition to a 12 to 18 hour GP IIb/IIIa infusion. Both groups demonstrated similar rates of ischemic complications; however, the bolus-only group experienced reduced vascular and bleeding complications and lower overall cost compared with the bolus plus infusion group. ...
The glycoprotein IIb/IIIa (GP IIb/IIIa) antagonists are the most recent additions to the antiplatelet agents available to the interventional radiologist. The currently available GP IIb/IIIa antagonists are abciximab, eptifibatide, and tirofiban. These medications have demonstrated excellent safety and efficacy in the setting of coronary arterial interventions. The fundamental benefit of the GP IIb/IIIa antagonists lies in their unique mechanism of action: the ability to prevent platelet aggregation, thrombus formation, and distal thromboembolism while preserving initial platelet binding to damaged vascular surfaces. A paucity of data exists regarding the role of GP IIb/IIIa inhibitors in peripheral vascular interventions. The GP IIb/IIIa antagonists would theoretically provide excellent antiplatelet therapy in patients undergoing any of a variety of endovascular interventions during which thrombosis or thromboembolism may endanger distal perfusion in patients with peripheral vascular disease. The goal of this summary is to review the indications for use, pharmacology, and evidence for efficacy of the GP IIb/IIIa antagonists in hopes of translating these data for application in the peripheral arterial circulation. Further research is necessary to determine how these agents may be safely used in combination with other anticoagulants or with stents, efficacy compared with standard regimens, success at preventing distal thromboembolism, and cost effectiveness.
... We used a single high-dose 20 mg (full vial) bolus of eptifibatide, and observed the level of platelet inhibition to be equivalent to the inhibition reported by the TEAM investigators after two weight-adjusted boluses. 45 Eptifibatide Dovepress submit your manuscript | www.dovepress.com ...
Introduction:
Acute coronary syndromes and non-Q-wave myocardial infarction are often initiated by platelet activation. Eptifibatide is a cyclic heptapeptide and is the third inhibitor of glycoprotein (Gp) IIb/IIIa that has found broad acceptance after the specific antibody abciximab and the nonpeptide tirofiban entered the global market. Gp IIb/IIIa inhibitors act by inhibiting the final common pathway of platelet aggregation, and play an important role in the management of acute coronary syndromes.
Aims:
This review assesses the evidence for therapeutic value of eptifibatide as a Gp IIb/IIIa inhibitor in patients with acute coronary syndromes.
Evidence review:
Several large, randomized controlled trials show that eptifibatide as adjunctive therapy to standard care in patients with non-ST segment elevation acute coronary syndrome is associated with a significant reduction in the incidence of death or myocardial infarction. Data are limited regarding the use of eptifibatide in patients with ST segment elevation myocardial infarction. Cost-effectiveness analysis indicates that eptifibatide is associated with a favorable cost-effectiveness ratio relative to standard care. According to US cost-effectiveness analysis about 70% of the acquisition costs of eptifibatide are offset by the reduced medical resource consumption during the first year. Eptifibatide was well tolerated in most of the trials. Bleeding is the most commonly reported adverse event, with most major bleeding episodes occurring at the vascular access site. Major intracranial bleeds, stroke, or profound thrombocytopenia rarely occurred during eptifibatide treatment.
Place in therapy:
Eptifibatide has gained widespread acceptance as an adjunct to standard anticoagulation therapy in patients with acute coronary syndromes, and may be particularly useful in the management of patients with elevated troponin or undergoing percutaneous coronary interventions.
... Recent studies on platelet glycoprotein IIb/IIIa receptor inhibitors (GPI) during percutaneous coronary intervention (PCI) have suggested that the administration of a bolus-only dose of GPI may be as effective, safer, and more cost-effective compared to a bolus plus infusion of GPI [1][2][3][4][5]. In the bolus-only GPI studies reported to-date, abciximab, eptifibatide, and tirofiban given as high-dose bolus (25 lg/kg) had similar in-hospital ischemic end points [2,5]. ...
To evaluate the long-term mortality after bolus-only administration of abciximab, eptifibatide, and tirofiban during percutaneous coronary intervention (PCI).
Studies on platelet glycoprotein IIb/IIIa receptor inhibitors (GPI) administered as bolus-only during PCI suggest that this strategy may be similar in efficacy, safer, and more cost-effective compared to a bolus plus infusion of GPI.
We evaluated 864 patients (abciximab = 274, eptifibatide = 361, and tirofiban = 229) who underwent PCI with a bolus-only regimen during January 2003 to August 2005.
After a median follow up of four (interquartile range, 3-4.5) years, there were a total of 95 (11%) deaths. The survival rate was 83% in the abciximab group, 91% in the eptifibatide group, and 93% in the tirofiban group (P = 0.003 by log-rank test). After adjustment for baseline clinical and procedural characteristics using a Cox proportional hazards model, the abciximab group had a significantly higher mortality compared to the eptifibatide group (P = 0.003; Hazard ratio (HR) for eptifibatide compared to abciximab was 0.49 (95% confidence intervals [CI]: 0.30-0.78). The long-term mortality was not significantly different in the tirofiban group compared to the abciximab group (P = 0.33) or the eptifibatide group (P = 0.20), perhaps because of shorter follow-up period and fewer patients in the tirofiban group.
When given as bolus-only during PCI, eptifibatide may improve long-term survival compared to abciximab.
Tilak Pasala, Prasongchai Sattayaprasert, Pradeep K Bhat, Ganesh Athappan, Sanjay Gandhi The Heart and Vascular Center, Case Western Reserve University/MetroHealth, Cleveland, OH, USA Abstract: Platelet adhesion and aggregation at the site of coronary stenting can have catastrophic clinical and economic consequences. Therefore, effective platelet inhibition is vital during and after percutaneous coronary intervention. Eptifibatide is an intravenous antiplatelet agent that blocks the final common pathway of platelet aggregation and thrombus formation by binding to glycoprotein IIb/IIIa receptors on the surface of platelets. In clinical studies, eptifibatide was associated with a significant reduction of mortality, myocardial infarction, or target vessel revascularization in patients with acute coronary syndrome undergoing percutaneous coronary intervention. However, recent trials conducted in the era of dual antiplatelet therapy and newer anticoagulants failed to demonstrate similar results. The previously seen favorable benefit of eptifibatide was mainly offset by the increased risk of bleeding. Current American College of Cardiology/American Heart Association guidelines recommend its use as an adjunct in high-risk patients who are undergoing percutaneous coronary intervention with traditional anticoagulants (heparin or enoxaparin), who are not otherwise at high risk of bleeding. In patients receiving bivalirudin (a newer safer anticoagulant), routine use of eptifibatide is discouraged except in select situations (eg, angiographic complications). Although older pharmacoeconomic studies favor eptifibatide, in the current era of P2Y12 inhibitors and newer safer anticoagulants, the increased costs associated with bleeding make the routine use of eptifibatide an economically nonviable option. The cost-effectiveness of eptifibatide with the use of strategies that decrease the bleeding risk (eg, transradial access) is unknown. This review provides an overview of key clinical and economic studies of eptifibatide well into the current era of potent antiplatelet agents, novel safer anticoagulants, and contemporary percutaneous coronary intervention. Keywords: eptifibatide, Integrilin®, glycoprotein IIb/IIIa inhibitors, percutaneous coronary intervention, acute coronary syndrome, coronary artery disease, cost-effectiveness
Platelet adhesion and aggregation at the site of coronary stenting can have catastrophic clinical and economic consequences. Therefore, effective platelet inhibition is vital during and after percutaneous coronary intervention. Eptifibatide is an intravenous antiplatelet agent that blocks the final common pathway of platelet aggregation and thrombus formation by binding to glycoprotein IIb/IIIa receptors on the surface of platelets. In clinical studies, eptifibatide was associated with a significant reduction of mortality, myocardial infarction, or target vessel revascularization in patients with acute coronary syndrome undergoing percutaneous coronary intervention. However, recent trials conducted in the era of dual antiplatelet therapy and newer anticoagulants failed to demonstrate similar results. The previously seen favorable benefit of eptifibatide was mainly offset by the increased risk of bleeding. Current American College of Cardiology/American Heart Association guidelines recommend its use as an adjunct in high-risk patients who are undergoing percutaneous coronary intervention with traditional anticoagulants (heparin or enoxaparin), who are not otherwise at high risk of bleeding. In patients receiving bivalirudin (a newer safer anticoagulant), routine use of eptifibatide is discouraged except in select situations (eg, angiographic complications). Although older pharmacoeconomic studies favor eptifibatide, in the current era of P2Y12 inhibitors and newer safer anticoagulants, the increased costs associated with bleeding make the routine use of eptifibatide an economically nonviable option. The cost-effectiveness of eptifibatide with the use of strategies that decrease the bleeding risk (eg, transradial access) is unknown. This review provides an overview of key clinical and economic studies of eptifibatide well into the current era of potent antiplatelet agents, novel safer anticoagulants, and contemporary percutaneous coronary intervention.
Antiplatelet therapy is a mainstay in the treatment of patients who have undergone percutaneous coronary intervention (PCI). Although the 2007 PCI treatment guidelines were published by the American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions, new clinical evidence has emerged, expanding our understanding of antiplatelet use and potentially affecting the treatment guidelines. For example, clinical trial results prompted a Science Advisory to recommend that dual therapy with aspirin and clopidogrel be used for longer periods—up to 1 year in patients who receive bare metal stents and at least 1 year in patients receiving drug-eluting stents. New trial results have also emerged regarding the use of glycoprotein IIb/IIIa antagonists such as abciximab, eptifibatide, and tirofiban. This article reviews the current recommendations for antiplatelet therapy in PCI patients, recent trial results, newly developed agents, ongoing clinical trials, and the future direction of antiplatelet therapy in patients who undergo PCI. © 2009 Wiley-Liss, Inc.
Introduction:
Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks the final common pathway of platelet aggregation. Its major adverse effect is bleeding. Balancing its safety and efficacy is paramount for its appropriate usage.
Areas covered:
The development of eptifibatide and its mechanism of action are explored. Clinical trials evaluating its efficacy and safety in a variety of clinical settings, as well as newer dosing regimens, are discussed. Readers will be able to understand the bleeding risks of eptifibatide in specific patient populations.
Expert opinion:
The risk of bleeding with eptifibatide needs to be weighed against the potential benefits. Understanding which patients are at higher risk of bleeding will help the clinician make appropriate decisions.
Primary percutaneous coronary intervention (PCI) is the best treatment of choice for acute ST segment elevation myocardial infarction (STEMI). This study aimed to determine the clinical outcomes of tirofiban combined with the low molecular weight heparin (LMWH), dalteparin, in primary PCI patients with acute STEMI.
From February 2006 to July 2006, a total of 120 patients with STEMI treated with primary PCI were randomised to 2 groups: unfractionated heparin (UFH) with tirofiban (group I: 60 patients, (61.2 ± 9.5) years), and dalteparin with tirofiban (group II: 60 patients, (60.5 ± 10.1) years). Major adverse cardiac events (MACE) during hospitalization and at 4 years after PCI were examined. Bleeding complications during hospitalization were also examined.
There were no significant differences in sex, mean age, risk factors, past history, inflammatory marker, or echocardiography between the 2 groups. In terms of the target vessel and vascular complexity, there were no significant differences between the 2 groups. During the first 7 days, emergent revascularization occurred only in 1 patient (1.7%) in group I. Acute myocardial infarction (AMI) occurred in 1 (1.7%) patient in group I and in 1 (1.7%) in group II. Three (5.0%) patients in group I and 1 (1.7%) in group II died. Total in-hospital MACE during the first 7 days was 4 (6.7%) in group I and 2 (3.3%) in group II. Bleeding complications were observed in 10 patients (16.7%) in group I and in 4 patients (6.7%) in group II, however, the difference was not statistically significant. No significant intracranial bleeding was observed in either group. Four years after PCI, death occurred in 5 (8.3%) patients in group I and in 4 (6.7%) in group II. MACE occurred in 12 (20.0%) patients in group I and in 10 (16.7%) patients in group II.
Dalteparin was effective and safe in primary PCI of STEMI patients and combined dalteparin with tirofiban was effective and safe without significant bleeding complications compared with UFH. Although there was no statistically significant difference, LMWH decreased the bleeding complications compared with UFH.
Outpatient practice after percutaneous coronary intervention (PCI) is gaining momentum due to constantly optimizing results. Furthermore, the availability of limited beds to handle the large volume of coronary interventions also promotes outpatient practice. The present report relates the current experience with same-day discharge and defines persisting challenges in promoting accelerated in-hospital turnover. Since the mid-1990s, there have been several reports on same-day discharge following uncomplicated procedures. Overall, the success of outpatient PCI practice is based on a few technological and pharmacological advances. First, the systematic use of stents and potent antiplatelet agents have revolutionized the acute success rates of PCI by virtually eliminating the risks of acute vessel closure within the first 24 h following a successful procedure. Second, the miniaturization of catheter sizes has also simplified access site management, accelerated ambulation time and limited the risks of puncture site bleeding. In this regard, the transradial approach initially described in Canada and later popularized in Europe has transformed the acute care of patients after PCI. Today, however, the practice of transradial PCI still varies largely from country to country. From the literature review, it appears that after a short period of observation (4 h to 6 h), the majority of eligible patients who have undergone uncomplicated coronary stenting can be discharged on the same day. Whereas implementation of same-day discharge to referring centres is simple, home discharge requires the development of structured outpatient programs with dedicated resources to assist the patient and family with short-term logistics, to provide reassurance, to serve as a 'safety net' and, lastly, to promote medication compliance and cardiovascular risk factor management. Further studies are required to better define the cost-minimization effects of outpatient PCI practice, as well as patient perception of fast-track PCI. It is proposed that outpatient PCI will likely continue to expand over the next decade.
For over one decade Glycoproteins IIb/IIIa inhibitors (GPI) have been administered to prevent coronary artery thrombosis. Initially these agents were used for acute coronary syndromes and subsequently as adjunctive pharmacotherapy for percutaneous coronary interventions (PCIs).
Most benefit of GPI emerged from reduction of ischemic events: mostly non-q-wave myocardial infarctions (NQWMIs) during PCI. However, individual randomized clinical trials could not demonstrate that any of these agents could significantly reduce mortality in any clinical subset of patients. Studies of employing prolonged oral GPI administration resulted in excessive death. The non-homogenous statistically-significant reduction of ischemic endpoints was accompanied by an excess of bleeding, vascular complications, and thrombocytopenia. The clinical and ecomomic burden of major bleeding and thrombocytopenia is substantial. The ACUITY trial has initiate a new debate regarding the efficacy and safety of GPI.
Selective “patient-tailored” use of GPI limited to moderate-high risk PCI patients with low bleeding propensity is suggested. Research of new algorithms emphasizing abbreviated GPI administration, careful access site and bleeding surveillance, in conjunction with lower doses of unfractionated heparin or new and safer anti-thrombins may further enhance patient safety.
No data are available on the long term efficacy of abciximab bolus-only with aspirin and clopidogrel pretreatment and systematic coronary stenting. Our objective was to evaluate the 3-year clinical outcomes in the EASY trial.
After a bolus of abciximab (0.25 mg/kg) and uncomplicated transradial coronary stenting, 1,005 patients were randomized either to same-day home discharge and no infusion (bolus-only group, n = 504) or to overnight hospitalization and 12 hours abciximab infusion (bolus + infusion group, n = 501). In contrast, 343 patients were not randomized after stenting for safety reasons and received abciximab bolus and infusion (not-randomized group). The rate of major adverse cardiovascular events (MACE), including death, myocardial infarction (MI) and target vessel revascularization (TVR) after percutaneous coronary intervention (PCI) was evaluated.
Up to 3 years, the incidence of MACE remained similar in the two randomized groups, 14% in bolus-only vs. 17% in bolus + infusion (P = 0.38). Similar efficacy was observed in subgroups analysis including higher-risk patients such as those with diabetes, unstable angina or non-ST elevation MI. Conversely, the incidence of MACE remained significantly higher in patients not-randomized post-PCI at all time intervals (P < 0.0001). The difference in outcomes between randomized and not-randomized patients was mostly accounted by the higher rates of MI, TVR as survival rate remained similar.
In patients pretreated with aspirin and clopidogrel and undergoing uncomplicated coronary artery stenting, abciximab bolus-only was associated with similar outcomes compared with bolus followed by infusion, up to 3 years after PCI. Conversely, patients with suboptimal results or clinical complications during PCI remained at higher risk of late revascularization or MI.
Previous studies on outcomes following percutaneous coronary intervention (PCI) have shown an increased rate of in-hospital mortality and vascular complications in women compared to men. The impact of gender on post-PCI outcomes in African-Americans has not been reported.
We retrospectively analyzed 835 consecutive African-American patients (n = 392 men and n = 443 women) who underwent PCI using a glycoprotein IIb/IIIa inhibitor (GPI) bolus-only strategy from January 2003 to August 2004 at a single institution. Baseline characteristics, procedural data, and in-hospital outcomes were recorded.
Women were older and had a higher mean body mass index (BMI) compared to men. Men were more likely to be smokers, more often had triplevessel disease and left ventricular dysfunction compared to women. There were no deaths or repeat revascularizations in either group. After adjustment for baseline risk factors and procedural characteristics, there was no significant difference in the composite endpoint of in-hospital death, myocardial infarction (MI), and repeat revascularization between men and women (6.38% in men and 2.48% in women; p = 0.051), but women had a higher rate of major and minor bleeding (0.5 vs. 2.5; p = 0.019; and 0.5 vs. 2.3; p = 0.021, respectively). On multiple logistic regression analysis, female gender was an independent risk factor for bleeding post-PCI (adjusted odds ratio [OR]-5.6, 95% confidence intervals [CI]: 1.15-27.45).
Although there is no difference in the in-hospital composite endpoint of death, MI, and repeat revascularization, African-American women are at increased risk for bleeding complications post-PCI, even when a GPI bolus-only strategy is used.
To assess the current practice of interventional cardiology in Israel.
Under the auspices of the 'Working group of interventional cardiology' of the 'Israel Heart Society,' a questionnaire regarding the practice of interventional cardiology sent to directors of interventional cardiology in all public hospitals.
Twenty centers received the questionnaires; however, complete data was obtained from 18. Most interventional cardiology units in Israel are merely engaged in percutaneous coronary interventions (PCIs). PCIs are executed mostly via the femoral artery, using almost exclusively stents, of which 36% were drug eluting. Noted was an infrequent use of other therapeutic, diagnostic devices, or femoral arteriotomy closure devices. Only 22% of the patients receive glycoprotein IIb/IIIa blockers (GPB). Most centers used conventional unfractionated heparin dosing (70 u/kg) and did not routinely monitor activated clotting time. Abciximab, bivalirudin or enoxaparine were rarely used. All laboratories performed both elective and emergency-PCI, although 12 facilities were not supported by on-site surgical backup.
Most cardiovascular intervention programs have restricted their activity to the coronary stenting, and are using a limited array of diagnostic and therapeutic devices, along with patient-tailored adjunctive pharmacotherapy, to sustain cost-effectiveness. Currently, ambulatory angiography and coronary interventions are not widely practiced in Israel.
Glycoprotein inhibitors (GPI) are viewed as beneficial adjunctive pharmacotherapy agents for percutaneous coronary interventions (PCIs). The major benefit of GPI is derived from the reduction of ischemic events (mostly non-Q-wave myocardial infarctions) during PCI. There is no single randomized clinical trial demonstrating that any of these agents significantly reduces mortality in any clinical subset of patients. Studies of sustained oral GPI resulted in excessive death and myocardial infarctions. Reduction of ischemic end points was counteracted by excessive bleeding, vascular complications, and thrombocytopenia. These complications bear considerable medical and economic impact. The Acute Catheterization and Early Intervention Triage Strategy trial demonstrated that GPI, when added to heparin, enoxaparine, or bivalirudin, do not reduce mortality or ischemic events but significantly increase bleeding complications. Major bleeding resulted in threefold mortality at 1 year. In view of available data, the use of GPI should be limited to moderate-risk to high-risk PCI patients with low bleeding propensity. Protocols of abbreviated GPI administration and careful bleeding surveillance, in conjunction with lower doses of unfractionated heparin or new and possibly safer antithrombins, can potentially improve patient safety.
Tirofiban administered at a bolus dose of 25 mcg/kg is associated with a higher level of platelet inhibition compared to that associated with the standard 10 mcg/kg tirofiban bolus dose. In our previous study on bolus-only glycoprotein IIb/IIIa receptor inhibition during percutaneous coronary intervention (PCI), the eptifibatide bolus-only group demonstrated similar efficacy, but significantly fewer bleeding complications compared to the abciximab bolus-only group.
To compare the in-hospital outcomes of high-dose (25 mcg/kg) tirofiban bolusonly vs. eptifibatide double bolus-only during PCI. In addition, the degree of platelet inhibition achieved by this novel tirofiban dosing strategy was assessed.
We retrospectively analyzed 876 consecutive patients who underwent PCI using a single high-dose bolus of tirofiban (25 mcg/kg) or eptifibatide (180 mcg/kg x 2, 10 minutes apart) from January 2003 to August 2005 in a single institution. Patients with ST-segment elevation myocardial infarction were excluded.
The percentage of platelet inhibition was 94% between 3-15 minutes post bolus of 25 mcg/kg of tirofiban. The platelet inhibition dropped to 92% at the end of the procedure (between 20-40 minutes) and to 74% at the time of sheath removal between 2-3 hours. After adjustment for the baseline and procedural characteristics, there was no difference in the composite endpoint of death, myocardial infarction, revascularization and bleeding complications (5.5% in tirofiban group vs. 5.3% in eptifibatide group; p = 0.79).
A single high-dose bolus of tirofiban rapidly achieves profound platelet inhibition and a significant antiplatelet effect is maintained until sheath removal. This dosing during PCI appears safe and compares favorably with eptifibatide bolus-only during PCI.
Long-term clinical follow-up has shown a significant benefit after percutaneous coronary intervention (PCI) for abciximab bolus followed by 12-hour infusion over placebo or bolus-only. With contemporary techniques and clopidogrel pretreatment, it is unknown whether the 12-hour infusion is still associated with a clinical benefit. The purpose of this study is to compare 6- and 12-month clinical outcomes in patients treated after PCI with abciximab bolus-only and abciximab bolus followed by 12-hour infusion.
After a bolus of abciximab (0.25 mg/kg) and uncomplicated transradial coronary stenting, 1,005 patients were randomized either to same-day discharge and no infusion of abciximab (bolus-only group, n = 504) or to overnight hospitalization and 12 hours (0.125 microg/[kg min]) of abciximab infusion (bolus + infusion group, n = 501). The rate of major adverse cardiovascular events (MACE) was evaluated at 30 days, 6 months, and 12 months.
At 30 days, the rate of MACE including death, myocardial infarction, and target vessel revascularization was similar in the 2 groups: 1.4% in the bolus-only group versus 1.8% in the bolus + infusion group (P = .63). At 6 months, the MACE rate was 5.6% in the 2 randomized groups. At 12 months, the MACE rate was also similar in both groups: 8.7% in the bolus-only group and 9.2% in the bolus + infusion group (hazard ratio 0.97, 95% CI 0.79-1.20, P = .80). Similar efficacy was also observed in several subgroups including higher-risk patients such as those with elevated troponin T before PCI.
In patients pretreated with clopidogrel and undergoing uncomplicated coronary artery stenting, there is no difference in the 6- and 12-month outcomes between patients treated with abciximab bolus-only versus those treated with bolus + infusion, a finding consistent with the initial 30-day outcomes.
The activated clotting time (ACT) has been reported to be sensitive to the anticoagulant activity of the low-molecular weight heparin dalteparin following intravenous (IV) administration.
To evaluate the feasibility of an ACT-guided dalteparin dose adjustment strategy during percutaneous coronary intervention (PCI).
This was a retrospective study of 104 consecutive patients who underwent PCI using an ACT-guided strategy of IV dalteparin. All patients received an initial IV bolus of 50 IU/kg of dalteparin. The minimum target ACT was 175 seconds for patients who received glycoprotein IIb/IIIa inhibitors and 200 seconds for patients who did not. Patients who did not achieve the target ACT after the initial 50 IU/kg were given supplemental boluses of dalteparin based on the assumption that for every additional 10 IU/kg of dalteparin, the ACT will rise by approximately 10 seconds.
After the initial bolus of dalteparin, the mean baseline ACT rose from 138 +/- 41 seconds to 235 +/- 78 seconds. In the 36 patients (35% of the study population) who required a mean supplemental dose of 14 +/- 6 IU/kg/kg, the mean ACT after the supplemental dose was 239 +/- 79 seconds. The composite endpoint of in-hospital death, target vessel revascularization (TVR) and myocardial infarction (MI) was 5.8%. Major and minor bleeding rates were 1% each. The composite incidence of death/MI/TVR was comparable to, and the bleeding complications were lower than, those achieved in the SYNERGY and STEEPLE trials.
ACT-guided dose adjustment of intravenously administered dalteparin during PCI appears to constitute a feasible strategy.
Among patients who underwent coronary stenting and were randomized to eptifibatide (n = 1,040) or placebo (n = 1,024), use of eptifibatide reduced initial procedural costs by 4,423 vs 61/patient (344, p = 0.002). When the cost of study drug was included, total initial hospital costs were increased by <10,632 vs $10,395, p <0.001).
To evaluate the differential effects of eptifibatide therapy on unstable angina vs non-ST elevation myocardial infarction at enrollment, since the separate impact on these two major diagnostic subsets of acute coronary syndrome patients has not been fully investigated.
We examined the 9461 patients in the PURSUIT trial (conducted between 1995 and 1997) to compare the effects of eptifibatide on unstable angina and myocardial infarction. The study showed greater and more consistent effects of eptifibatide therapy on unstable angina than non-ST elevation myocardial infarction in reducing 30-day death/(re)infarction (from the unadjusted rate of 13.0% to 11.2%, P=0.059 for unstable angina; and 18.9% to 17.9%, P=0.387 for myocardial infarction), especially among patients who underwent early percutaneous coronary intervention (odds ratios=0.49 and 0.86, 95% confidence intervals=0.30-0.80 and 0.53-1.42, respectively, for unstable angina and myocardial infarction). The only subgroup for whom the benefit of eptifibatide was not evident was female myocardial infarction patients who did not undergo early percutaneous coronary intervention.
These data suggest that eptifibatide benefited unstable angina patients more than myocardial infarction patients, especially among those who underwent early percutaneous coronary intervention, and support its use as concomitant therapy with early percutaneous coronary intervention especially in female myocardial infarction patients.
This is a randomized head-to-head comparison of the 3 glycoprotein IIb/IIIa inhibitors during high-risk percutaneous coronary intervention. The study showed that in the setting of >90% platelet inhibition, achieved by an additional half bolus in 48% of patients, similar periprocedural enzyme release and 30-day major adverse cardiac events can be accomplished regardless of the type of glycoprotein IIb/IIIa inhibitor used.