Figure 1 - uploaded by Jean M Nappi
Content may be subject to copyright.
Suggested algorithm for the use of glycoprotein IIb/IIIa receptor inhibitors. a ACC = American College of Cardiology; AHA = American Heart Association ; CABG = coronary artery bypass graft; CAD = coronary artery disease; LMWH = low-molecular-weight heparin; MI = myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation MI; UA = unstable angina; UFH = unfractionated heparin. a See Appendix I for definition of acronyms. b Predictors of success and complications are based on target lesion anatomic factors (lesion length, tortuosity, angulated segments, total occlusions, protection of major side branches, degenerated vein grafts with friable lesions), clinical factors (advanced age, female gender, unstable angina, congestive heart failure, diabetes , and multivessel CAD), among others. 81 c
Source publication
To review the contemporary role of the glycoprotein (GYP) IIb/IIIa receptor inhibitors abciximab, eptifibatide, and tirofiban in patients undergoing percutaneous coronary intervention (PCI) and those with an acute coronary syndrome (ACS), and to provide an algorithm based on currently available evidence for specific agents.
Primary articles were id...
Similar publications
To determine clinical characteristics, management, and in-hospital outcomes of diabetic and non-diabetic patients admitted with acute coronary syndrome (ACS) in Oman.
Data were analyzed from 1583 consecutive patients admitted to various hospitals in Oman with ACS from May 8 to June 6, 2006, and from January 29 to June 29, 2007, as part of the Gulf...
To assess the safety and effectiveness of abciximab in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in clinical practice.
Data were analysed of 2184 consecutive patients treated with primary PCI for acute STEMI and either concomitant abciximab or no glycoprotein IIb/IIIa inhi...
Citations
... During PCI, abrupt vessel closure can occur as a result of coronary endothelium damage and subsequent platelet-mediated thrombosis caused by balloon inflation. 2,4 Moreover, stents can incite platelet aggregation owing to the procoagulant nature of their metallic surface, by causing endothelial damage and displacing preformed plaques along the vessel wall. 2 For these reasons, current PCI guidelines recommend routine pretreatment with aspirin and a thienopyridine before the procedure, as well as periprocedural therapy with unfractionated heparin (UFH) and a glycoprotein (GP) IIb-IIIa inhibitor. 1,3 In particular, GP IIb-IIIa inhibitor therapy proved to decrease the rate of mortality, myocardial infarction, and repeat revascularizations at 30 days in a varied population of patients undergoing PCI. ...
... 1,3 In particular, GP IIb-IIIa inhibitor therapy proved to decrease the rate of mortality, myocardial infarction, and repeat revascularizations at 30 days in a varied population of patients undergoing PCI. 4,5 Although periprocedural use of UFH with GP IIb-IIIa inhibitor therapy is a common approach in PCI, recent studies with the direct thrombin inhibitor bivalirudin, with provisional use of a GP IIb-IIIa inhibitor, have challenged this approach in elective procedures. One of the limitations of UFH is that it must bind to both antithrombin and an exosite on thrombin concurrently to exert its anticoagulant effect, and it cannot inhibit clot-bound thrombin because of inaccessibility of its binding site. ...
To perform a cost-effectiveness analysis comparing three treatment approaches during nonurgent percutaneous coronary intervention (PCI): bivalirudin with provisional glycoprotein (GP) IIb-IIIa inhibitor therapy, unfractionated heparin (UFH) with eptifibatide, and UFH with abciximab.
Literature-based decision model from an institutional perspective.
Patient data from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 study and three other randomized controlled trials that included UFH and routine GP IIb-IIIa inhibitor (eptifibatide or abciximab) therapy. All included studies were comparable based on patient population, procedural techniques, and general treatment approaches.
We included patient populations undergoing contemporary nonurgent PCI to identify probabilities of success or complications (myocardial infarction, urgent revascularization, thrombocytopenia, and major or minor bleeding at 30 days). Costs were assigned to each outcome by incorporating diagnosis-related group-- and/or Current Procedural Terminology--associated costs, institutional drug acquisition costs, and unit replacement costs of platelets and red blood cells. In the base-case analysis, the use of bivalirudin with provisional GP IIb-IIIa inhibitor therapy dominated the UFH and planned GP IIb-IIIa inhibitor approach: UFH with eptifibatide was 74 US dollars more expensive and 1.2% less effective, and UFH with abciximab was 777 US dollars more expensive and 2.3% less effective. Sensitivity analyses indicated that the model results were robust, but also revealed that bivalirudin lost its cost-effectiveness, resulting in UFH with eptifibatide becoming more cost-effective, when two or more vials of bivalirudin were necessary in greater than 27% of cases or when the use of provisional GP IIb-IIIa inhibitor therapy exceeded 20%.
This analysis indicates that bivalirudin with provisional GP IIb-IIIa inhibitor therapy is the most cost-effective antithrombotic treatment strategy in nonurgent PCI when its use and dosing are consistent with the REPLACE-2 trial.
Development of thrombi can lead to various life-threatening cardiovascular and neurological events, and the role of platelets in thrombus formation is well known. Antiplatelet agents are used in the treatment, as well as both primary and secondary prevention, of various disease states or clinical scenarios. Mechanisms of action, reversibility, metabolism, drug interactions, duration of action, and other characteristics differ widely among the different classes of, and between individual, antiplatelet agents. An overview of the pharmacology, clinical indications, and monitoring considerations of antiplatelet drugs is included.
The endothelium is an uninterrupted, smooth, and nonthrombogenic surface that not only forms a highly selective permeability barrier, but also synthesizes and releases a plethora of vasoactive substances, notably nitric oxide, involved in regulating vascular tone and platelet aggregation. The underlying cause of most forms of cardiovascular disease, notably myocardial infarction and stroke, is atherosclerosis, a process that is initiated by endothelial dysfunction and sustained by intimal thickening, deposition of (low-density) lipoprotein, and invasion by macrophages and other white blood cells. In addition, endothelial activation leads to the expression and release of proinflammatory surface molecules such as tissue factor. Severe coronary stenosis causes angina, while plaque rupture and endothelial erosion release highly procoagulant plaque content into the bloodstream, activating platelets and initiating the coagulation cascade, with thrombus formation and vessel occlusion. Percutaneous coronary intervention, platelet inhibitors, and anticoagulants help to restore patency in acute occlusion, while long-term primary and secondary prevention with statins, angiotensin-converting-enzyme inhibitors, angiotensin-II receptor blockers, and calcium channel blockers enhances endothelial function. This review updates the authors' previous publications, focusing on blood/vessel wall interaction and its importance for atherothrombosis and its management.
Purpose
To determine if hospital consultant recommendations were clinically applicable to the cardiac catheterization laboratory and to compare medication usage in percutaneous coronary intervention (PCI) to those goals.
Methods
The medical records of 96 adults on whom PCI had been performed over a 6-month period were reviewed retrospectively. Only PCIs that included intracoronary stent placement were considered. The primary end point was to determine if abciximab usage was 15% or less in all PCI cases. Secondary end points evaluated the use of abciximab, eptifibatide, and bivalirudin based on the acuity of the clinical syndrome.
Results
Abciximab, eptifibatide, and bivalirudin monotherapy were used in 16.7%, 40.6%, and 42.7% of all cases, respectively. The total consumption of abciximab exceeded the primary end point by 1.7%. Eptifibatide usage was 71% of all glycoprotein (GP) IIb/IIIa inhibitors, less than the 85% target proposed by the hospital consultants. Bivalirudin monotherapy surpassed eptifibatide as the antithrombotic of choice across all PCI cases. The use of provisional GP IIb/IIIa inhibitors in conjunction with bivalirudin was 8.3%, more than the 5% target specified by the consultants. Emergent PCIs comprised 41% of all cases sampled.
Conclusion
This 6-month retrospective survey demonstrated that the use of abciximab exceeded the percentage recommended by consultants. However, given the large percentage of emergent PCIs during the time period and the literature supporting the use of abciximab in emergent PCIs, a change in GP IIb/IIIa inhibitor usage patterns was not considered necessary.
Background
Platelet glycoprotein (GP) IIb/IIIa antagonists have been increasingly used in acute coronary artery syndrome to prevent myocardial infarction. The major drawback is that occasionally they may cause severe bleeding complication. The administration of GPIIb/IIIa antagonists induces a condition closely resemble to Glanzmann’s thrombasthenia, an inherited abnormality of GPIIb/IIIa. Activated recombinant coagulation factor VII (rFVIIa) is currently approved for the treatment or prevention of bleeding in patients with Glanzmann’s thrombasthenia. We investigated the effect of rFVIIa on platelet function in the presence of GPIIb/IIIa antagonists.
Materials and Methods
Abciximab or Eptifibatide was added to normal whole blood samples in the absence or presence of thrombin inhibitor (heparin, hirudin, or PPACK). The effect of rFVIIa at therapeutic concentrations (0.35–7 nmol/1) on GPIIb/IIIa-inhibited platelets was assessed using platelet aggregometry and platelet function analyzer (PFA-100). In addition, the effect of rFVIIa on thrombocytopenic samples in the presence of Abciximab was also studied.
Results
rFVIIa at concentrations used in the study completely corrected the closure times of the samples with GPIIb/IIIa-inhibited platelets, while only a partial correction could have been observed with aggregometry. This effect was also evident in the presence of thrombin inhibitors or thrombocytopenia.
Conclusions
rFVIIa completely restores the function of GPIIb/IIIa-inhibited platelets in vitro as assessed by PFA-100 experiments. Further studies are needed to correlate this in vitro finding with in vivo conditions.
Der Schlaganfall stellt die dritthäufigste Erkrankung mit Todesfolge dar und ist Hauptursache langzeitiger Behinderungen. Pathophysiologisch besitzen arterio-arterielle Embolien die größte ätiopathogenetische Relevanz für den ischämischen Hirninfarkt. Die schnelle Revaskularisation mittels systemischer oder lokaler Fibrinolyse zeigt zwar eine protektive Wirkung auf die Läsionsentwicklung, sie wird jedoch durch erhebliche Nebenwirkungen, insbesondere cerebrale Blutungen, limitiert. Darüberhinaus berücksichtigen die aktuell engesetzten Behandlungsstrategien die pathophysiologischen Zusammenhänge zwischen Thrombolyse und Thrombenbildung nur unzureichend. In der vorliegenden Schrift werden eigene klinische Studien zur Bedeutung der Thrombozyten in der Akutphase des Schlaganfalles und ein neuer Ansatz in der Akuttherapie vorgestellt. Die Entwicklung neuartiger Plättchen Glykoprotein IIb/IIIa-Antagonisten ermöglicht heute eine spezifische Thrombozytenfunktionshemmung. Mit dem nicht-peptidergischen Rezeptorantagonisten Tirofiban liegt ein sehr gut steuerbarer, selektiver Plättchenaggregationshemmer vor. Cerebrale Mikroembolien können damit komplett und reversibel gehemmt werden. In der Kombination mit niedrigdosierten Thrombolytika zeigt sich eine sehr gute Rekanalisationsrate bei embolischen cerebralen Gefäßverschlüssen, ohne daß eine erhöhte Blutungsrate in Kauf genommen werden muß. Rotationsthrombelastographische Messungen in der Akutphase lassen vermuten, daß möglicherweise bei Non-Respondern eine individuelle Dosisanpassung zur Steuerung der Lyse notwendig wird. Zudem konnte gezeigt werden, daß die selektive Blockade thrombozytärer alphaIIb beta3 Rezeptoren auch jenseits der hyperakuten Phase eine mögliche protektive Wirkung beim ischämischen Insult entfaltet. Anhand kernspintomographisch definierter Parameter ergab sich der Befund, daß die endgültige Hirninfarktgröße in der Behandlungsgruppe signifikant kleiner war als in der Placebogruppe. Diese Beobachtung ist kompatibel mit der Hypothese, daß die (lokale) Aktivierung von Thrombozyten beim ischämischen Hirninfarkt zu Mikrozirkulationsstörungen und damit zu einem auch über Stunden bis Tage nach Insultbeginn anhaltenden Läsionswachstum führt. In Analogie zur kardiovaskulären experimentellen und klinischen Forschung stellt die kombinierte Anwendung niedrigdosierter Fibrinolytika mit Plättchen Glykoprotein IIb/IIIa-Antagonisten ein insgesamt schlüssiges Konzept in der Behandlung thrombembolischer cerebraler Ischämien dar. Die bisherigen Daten sind Grundlage für randomisierte, kontrollierte klinische Studien, wie sie in Düsseldorf bereits begonnen wurden. Die Perspektiven lassen in den nächsten Jahren eine verbesserte Akutbehandlung von Insultpatienten erwarten, die im wesentlichen auf einer verbesserten Diagnostik mit der Möglichkeit zur raschen Stratifizierung und einem differenzierten Einsatz bereits entwickelter pharmakologischer Substanzen beruht.
As our understanding of integrins as multifunctional adhesion and signaling molecules has grown, so has their recognition as potential therapeutic targets in human diseases. Leukocyte integrins are of particular interest in this regard, as they are key molecules in immune-mediated and inflammatory processes and are thus critically involved in diverse clinical disorders, ranging from asthma to atherosclerosis. Antagonists that interfere with integrin-dependent leukocyte trafficking and/or post-trafficking events have shown efficacy in multiple preclinical models, but these have not always predicted success in subsequent clinical trials (e.g., ischemia-reperfusion disorders and transplantation). However, recent successes of integrin antagonists in psoriasis, inflammatory bowel disease, and multiple sclerosis demonstrate the tremendous potential of antiadhesion therapy directed at leukocyte integrins. This article will review the role of the leukocyte integrins in the inflammatory process, approaches to targeting leukocyte integrins and their ligands, and the results of completed clinical trials.
Acute ischaemic stroke is the result of an abrupt interruption of focal cerebral blood flow. In the majority of cases, this interruption is caused by an acute thromboembolism. Based on clinical experience in the treatment of acute coronary syndromes, platelet glycoprotein (GP) IIb/IIIa receptor antagonists alone, in combination with reduced doses of thrombolytic agents, or as complementary therapy for short-term mechanical interventions merit consideration as a class of agents with potential use in ischaemic stroke. Research to date and extrapolation from the cardiac literature suggest significant, but as yet unproven, potential for the use of GP IIb/IIIa receptor antagonists in the treatment of acute ischaemic stroke. This potential exists both at the site of the thromboembolic occlusion and at the distal microvascular level. This article reviews the scientific rationale and available evidence for the potential use of platelet GP IIb/IIIa receptor antagonists in acute ischaemic stroke.
To evaluate the safety and efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein llb/llla receptor, in the treatment of unstable angina and myocardial infarction without persistent ST elevation (acute coronary syndrome, ACS), a total of 200 patients were randomly assigned to a heparin group and a tirofiban+heparin group on double-blind basis and the treatment effects of the two protocols on ACS were compared when the patients of both groups were taking aspirin at the same time. The composite primary end-point events consisted of death, myocardial infarction, or refractory ischemia. Our results showed that the frequency of the composite primary end point events in 30 days was lower in tirofiban+heparin group as compared with that of heparin group (13.9% vs 29.3 %, P=0.010). The rates of the other composite end point events in the tirofiban+heparin group were also lower than those in the heparin group in 4.5 days and in 30 days. Bleeding complication occurred in 7.0% of the patients receiving heparin alone and in 12.7% of the patients receiving tirofiban and heparin in combination (P=0.1717). The study showed that the incidence of ischemic events in patients with ACS receiving tirofiban+heparin was lower when compared with that of patients who received only heparin and aspirin, suggesting that tirofiban might be of special value in the treatment of ACS.
