High-risk Coronary Angioplasty Research Articles

Results of a pilot clinical trial of the safety and efficacy of an original glycoprotein IIb/IIIa receptor inhibitor in acute coronary syndrome

Aim. To study the safety and efficacy of Angipure in acute ST-segment elevation coronary syndrome (STE-ACS) and high-risk percutaneous transluminal coronary angioplasty (PTCA) compared with eptifibatide.Material and methods. The study included 157 patients with STE-ACS. High-risk PTCA included massive or total coronary artery thrombosis, noreflow/slow-reflow phenomenon, and acute stent thrombosis. Fifty-five people received Angipure at a dose of 0,72 mg/kg, 52 — at a dose of 0,40 mg/kg, while 50 patients received eptifibatide (Integrilin). We conducted clinical and laboratory studies, electrocardiography (ECG), coronary angiography.Results. According to the criteria "Frequency and severity of hemorrhagic events, including hemorrhagic stroke", "Frequency, severity of other adverse events", there were no differences in safety between Angipure at doses of 0,40 and 0,72 mg/kg and eptifibatide. Complaints, clinical symptoms, vital signs, complete blood count, biochemical and coagulation tests, ECG in patients of different groups were similar and had unidirectional dynamics. The use of Angipure or eptifibatide was considered effective if no adverse outcomes (death, recurrent acute ischemic event, need for urgent revascularization) were observed within 30 days. There were no lethal outcomes. One repeated acute ischemic event was registered in each group. In groups of patients receiving Angipure 0,40 mg/kg and eptifibatide, urgent revascularization was required once each.Conclusion. Angipure and eptifibatide have similar safety and efficacy.

High-risk percutaneous coronary angioplasty with rotational atherectomy and left ventricular assist device of chronically occluded left ascending artery in an obese patient with very low ejection fraction.

High-risk percutaneous coronary angioplasty with rotational atherectomy and left ventricular assist device of chronically occluded left ascending artery in an obese patient with very low ejection fraction.

Perfluorocarbons: Knowledge Gained From Clinical Trials.

Research into potential use of perfluorocarbons for liquid ventilation and as oxygen delivery agents in humans has been underway since the 1960s. While partial liquid ventilation with perfluorocarbons showed promise in animal models and early human investigation, randomized controlled human trials failed to show benefit and an elevated rate of adverse events. Initial approval of Fluosol-DA (Green Cross Corporation, Osaka, Japan) by the United States Food and Drug Administration as an oxygen delivery agent for use in high-risk coronary angioplasty represents the only approved application of these compounds to supplement tissue oxygenation, but the compound was rendered obsolete and removed from the market with the development of advanced angioplasty catheters in the 1990s. Second-generation perfluorocarbons were developed with a higher capacity to increase the amount of oxygen dissolved in the fluid phase of blood. Early clinical trials of perflubron emulsion in non-cardiac and cardiac surgery were promising, but dose restriction and the requirement for high inspired oxygen concentration to maximize oxygen delivery for prolonged periods of time limited the clinical utility as a replacement for the oxygen carrying capacity of red blood cells. Identification of excess serious adverse events in treated patients resulted in discontinuation of pivotal clinical trials. Continued research investigating different formulations of perfluorocarbons has shown promise in animal studies, but continued research is necessary to prove safety and efficacy in humans.

The Impella Device: Historical Background, Clinical Applications and Future Directions.

The Impella device is a catheter-based miniaturized ventricular assist device. Using a retrograde femoral artery access, it is placed in the left ventricle across the aortic valve. The device pumps blood from left ventricle into ascending aorta and helps to maintain a systemic circulation at an upper rate between 2.5 and 5.0 L/min. This results in almost immediate and sustained unloading of the left ventricle, while increasing overall systemic cardiac output. The most common indications for using the Impella device are in the treatment of acute myocardial infarction complicated by cardiogenic shock and to facilitate high risk coronary angioplasty. Other indications include the treatment of cardiomyopathy with acute decompensation, postcardiotomy shock, and off-pump coronary bypass surgery. A growing body of observational and registry data suggest a potentially valuable role for the Impella system in reducing the mortality associated with cardiogenic shock. However, there are, as of yet, no randomized controlled trial data supporting this observation.

Mechanisms of C-reactive protein, interleukin-6 and soluble CD40L blood concentration changes after coronary stent implantation

Background: The pathway linking inflammation and thrombosis has been extensively studied. Experimental data support that arterial thrombosis also induces a detectable inflammatory response, which in turn, activates prothrombotic pathways closing a vicious circle that interconnects inflammation and thrombosis. Aim: We designed this study to investigate the causes of inflammatory markers increase after coronary angioplasty. Methods: We analyzed the interrelationship of thrombotic and inflammatory markers and the effect of blocking thrombus formation on the inflammatory response in 50 patients undergoing high thrombotic risk coronary angioplasty. The relationship of platelet number to soluble CD40 Ligand, Interleukin-6 and C-reactive protein blood levels was studied. Half of the study population was treated with standard antithrombotic drugs and the other half with the standard therapy plus platelet GP IIb-IIIa receptor inhibitor Eptifibatide. Results: There was a clear correlation between basal platelet count and sCD40L basal levels, post-angioplasty sCD40L increase and post-angioplasty IL-6 levels and post-angioplasty IL-6 levels with post-angioplasty CRP levels. Postangioplasty CRP, IL-6 and sCD40L blood levels were influenced by GP IIb-IIIa treatment in patients with angiographic thrombus. Conclusion: Platelet aggregation induces a proinflammatory response which is blocked by a GP IIb-IIIa inhibitor agent, particularly in patients with patent angiographic thrombus.

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

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

Percutaneous Impella Recover circulatory support in high-risk coronary angioplasty

Due to the increased life expectancy derived from better conditions of life and improved medical technology, interventional cardiologists are facing challenging procedures in older and much more delicate patients, in whom percutaneous coronary intervention is generally considered less dangerous than cardiac surgery. We present two recent cases of high-risk complete myocardial revascularization in patients older than 80 years assisted by the Impella Recover 2.5. In our initial experience this device proved to be relatively easy to set up and hemodynamically useful for patients with left ventricular dysfunction and end-stage coronary atherosclerosis.

First use of a novel plug-and-play percutaneous circulatory assist device for high-risk coronary angioplasty

Novel circulatory assist devices provide hemodynamic stability in high risk coronary interventions. They ensure sufficient organ perfusion during transfer in case of procedural failure or cardiogenic arrest. We describe the first human use of a novel plug-and-play circulatory assist device for high risk coronary angioplasty. An 84 year old lady suffered syncope with complex fracture of the left forearm. Her syncope was related to a subtotal stenosis of the left main coronary artery associated with an acute myocardial infarction. Additional risk factors were previous cardiac surgery, pulmonary disease, diabetes mellitus, and renal insufficiency. Coronary angiography revealed stenosis of both coronary ostia. The emergency assist device LIFEBRIDGE was connected with the patient's circulation by percutaneous cannulation (15F and 17F) of the femoral artery and vein. Stent implantation was performed in both coronary ostia by Judkin's technique. The cannulas were removed two hours after the intervention by local compression. Osteosynthesis of the left radius and ulna was performed five days later under regional anesthesia. The patient was discharged without any complains on day 10. This case illustrates the safe and easy use of a novel plug-and-play percutaneous circulatory assist device for high risk interventions. It may be recommended for use in emergency situations.

Drive-Through Angioplasty

In this issue of Circulation , Bertrand et al1 report the results of the Early Discharge after Transradial Stenting of Coronary Arteries (EASY) Study. After receiving a standard bolus of abciximab and undergoing a successful and uncomplicated transradial stent placement, 1005 patients were randomized to a traditional strategy with overnight hospitalization or early discharge after 4 to 6 hours. All patients received aspirin, clopidogrel, and a bolus dose of abciximab before their procedure. Those in the traditional strategy group also received a 12-hour abciximab infusion, whereas those in the early discharge group did not. The goal of the EASY study was to show that stent implantation by the radial approach with only a bolus of abciximab and then early discharge was not inferior to the traditional strategy in terms of effectiveness and safety. The primary composite end point was the 30-day incidence of death, any myocardial infarction, unplanned revascularization, major bleeding, repeat hospitalization, access-site complications, or severe thrombocytopenia. On the basis of their data, the authors concluded that the abbreviated abciximab therapy with same-day discharge was clinically not inferior to the traditional strategy after uncomplicated stent placement. Article p 2636 With healthcare costs increasing, strategies to limit expenditures are popular and deserve careful examination. Accepted cardiology practice has moved toward dramatically shortened hospital stays for diagnostic coronary angiography and percutaneous coronary intervention (PCI) as well as many other procedures. The present study suggests that many patients who undergo PCI could be managed safely as outpatients. Substantial accomplishments in the practice of PCI have resulted in the excellent success and safety of the procedure we now observe, but are we ready for routine outpatient PCI? The use of radial artery access has been well described in the literature. Despite studies demonstrating the feasibility, safety, and acceptance by patients of this …

Mechanische Herz-Kreislauf-Unterstützung in der Kardiologie

One out of 13 patients with an acute myocardial infarction is endangered of cardiogenic shock. In addition, acute valvular leakage, shunt vitiae, and acute myocarditis can lead to acute myocardial failure. As a therapeutic option, mechanical assist devices offer cardiac support and hemodynamic stabilization under these circumstances. The following minimal-invasive devices are used in cardiology and intensive care medicine: intra-aortic balloon pulsation (IABP), intra-vascular axial screw pumps, extra-corporal centrifugal pumps with and without additional membrane oxygenator. The IABP improves left ventricular function by a systolic reduction of the after-load, and an increase of diastolic blood pressure dependent on myocardial function. In contrast, axial screw pumps and centrifugal pumps can provide circulatory support independently of myocardial function. Mechanical assist devices can prevent irreversible damage not only by offering a reduction of myocardial work load, but also by improving organ perfusion in cardiogenic shock situations. Another indication for mechanical circulatory support depicts high-risk coronary angioplasty if the left ventricular ejection fraction is severely reduced or the target vessel supplies more than 50 % of vital myocardium. In case of irreversible heart failure, turbine pumps or centrifugal pumps offer a stabilization for the patient's transfer to a cardiac surgery center. They can also be used for bridging to heart transplantation in acute situations. Technical improvements will enhance the use of mechanical assist devices in the near future. Especially the development of portable emergency devices will enrich therapeutic possibilities in cardiology and intensive care medicine.

Successful high-risk coronary angioplasty in a patient with cardiogenic shock under circulatory assist with a 16F axial flow pump

We report the case of a 75-year-old patient who suffered from subacute myocardial infarction and severely impaired left ventricular ejection fraction (EF: 17%). Using a novel 16F left ventricular assist device we performed an angioplasty of the right coronary artery, and of the left anterior descending artery. As a result of the circulatory support the patient recovered from cardiogenic shock within 8 hr. At a pump speed of 45,000 rpm the axial flow pump generated flow rates up to 3.3 l/min. The 16F pump cannula was removed using local compression. The EF was 51% at 30-day follow-up examination.

The additive value of tirofiban administered with a high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: The ADVANCE Trial

The additive value of tirofiban administered with a high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: The ADVANCE Trial

The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: The advance trial

ObjectivesWe sought to determine the safety and efficacy of high-dose bolus (HDB) tirofiban in high-risk patients undergoing percutaneous coronary intervention (PCI). BackgroundThe use of HDB tirofiban in the catheterization laboratory is controversial. In particular, in patients with acute coronary syndromes undergoing PCI, there is no evidence that tirofiban administered in the catheterization laboratory is superior to heparin alone. This finding probably reflects the suboptimal platelet inhibition when tirofiban is employed at RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) regimen. MethodsA total of 202 patients (mean age 69 ± 8 years; 137 males [68%]) undergoing high-risk PCI, pretreated with thienopyridines, were consecutively randomized to HDB tirofiban (25 μg/kg/3 min, and infusion of 0.15 μg/kg/min for 24 to 48 h) or placebo immediately before the procedure and then followed for a median time of 185 days (range 45 to 324 days) for the occurrence of the primary composite end point of death, myocardial infarction, target vessel revascularization (TVR), and bailout use of glycoprotein (GP) IIb/IIIa inhibitors. ResultsThe cumulative incidence of the primary end point was 35% and 20% in placebo and HDB tirofiban groups, respectively (hazard ratio 0.51, 95% confidence interval 0.29 to 0.88; p = 0.01). This difference was mainly due to the reduction of myocardial infarction and bailout use of GP IIb/IIIa inhibitors, with no significant effect on TVR or death. The safety profile did not differ between tirofiban and placebo. ConclusionsThe use of tirofiban, when administered at HDB, is safe and significantly reduces the incidence of ischemic/thrombotic complications during high-risk PCI.

Elective versus provisional intra-aortic balloon pumping in high-risk percutaneous transluminal coronary angioplasty

Background Elective intra-aortic balloon pump (IABP) support may reduce acute complications occurring during percutaneous coronary interventions (PCI) in patients with severe depression of the left ventricular ejection fraction (EF ≤ 30%). Methods Since February 1998, 133 consecutive patients with EF ≤30% underwent elective PCI in our institution; 61 had elective preprocedural IABP support (group A) and 72 patients had conventional PCI (group B). Jeopardy score was calculated in each patient from the coronary angiograms to quantify the myocardium at risk. Results EF was similar in the 2 groups. Jeopardy score was higher in group A (8.0 ± 2.8 vs 6.7 ± 2.4, P = .008). The other principal clinical and angiographic characteristics were similar in the 2 groups. Severe hypotension and/or shock occurred in 11 patients, all in group B ( P = .001). All required urgent IABP support, and 3 eventually died. Intraprocedural major adverse cardiac and cerebral events (eg, myocardial infarction, severe hypotension and/or shock, urgent bypass surgery, stroke, and death) were higher in group B (17% vs 0%, P = .001). By stepwise logistic regression analysis, elective IABP support (odds ration [OR] 0.11 [95% CI 0.21-0.60], P = .011), jeopardy score (OR 5.37 [95% CI 1.10-8.70], P = .040), and female sex (OR 2.72 [95% CI 1.85-3.10], P = .015), were the correlates of intraprocedural events. Conclusions This study supports the potential usefulness of elective versus provisional IABP to prevent intraprocedural major adverse cardiac and cerebral events in high-risk PCI. (Am Heart J 2003;145:700-7.)

Usefulness of percutaneous left ventricular assistance to support high-risk percutaneous coronary interventions

Percutaneous coronary intervention (PCI) has been proposed as a measure to alleviate symptoms and improve prognosis in patients with atherosclerotic heart disease and depressed heart function. Nonetheless, the risk of ischemic complications during or after the procedure is potentially increased in these patients. A number of supportive techniques have been described for high-risk angioplasty 1 Shawl F.A. Quyyumi A.A. Bajaj S. Hoff S.B. Dougherty K.G. Percutaneous cardiopulmonary bypass-supported coronary angioplasty in patients with unstable angina pectoris or myocardial infarction and a left ventricular ejection fraction ≤25%. Am J Cardiol. 1996; 77: 14-19 Abstract Full Text PDF PubMed Scopus (25) Google Scholar , 2 Scholz K.H. Dubois-Rande J.L. Urban P. Morice M.C. Loisance D. Smalling R.W. Figulla H.R. Clinical experience with the percutaneous hemopump during high-risk coronary angioplasty. Am J Cardiol. 1998; 82: 1107-1110 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar , 3 Dubois-Rande J.L. Teiger E. Garot J. Aptecar E. Pernes J.M. Tixier D. Gueret P. Loisance D. Dupouy P. Effects of the 14F hemopump on coronary hemodynamics in patients undergoing high-risk coronary angioplasty. Am Heart J. 1998; 135: 844-849 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar , 4 Schreiber T.L. Kodali U.R. O’Neill W.W. Gangadharan V. Puchrowicz-Ochocki S.B. Grines C.L. Comparison of acute results of prophylactic intraaortic balloon pumping with cardiopulmonary support for percutaneous transluminal coronary angioplasty (PCTA). Cathet Cardiovasc Diagn. 1998; 45: 115-119 Crossref PubMed Scopus (22) Google Scholar , 5 Kaul U. Sahay S. Bahl V.K. Sharma S. Wasir H.S. Venugopal P. Coronary angioplasty in high risk patients comparison of elective intraaortic balloon pump and percutaneous cardiopulmonary bypass support—a randomized study. J Interv Cardiol. 1995; 8: 199-205 Crossref PubMed Scopus (18) Google Scholar ; however, no single approach has achieved wide acceptance. Limited effectiveness in the actual support 6 Taguchi I. Ogawa K. Oida A. Abe S. Kaneko N. Sakio H. Comparison of hemodynamic effects of enhanced external counterpulsation and intra-aortic balloon pumping in patients with acute myocardial infarction. Am J Cardiol. 2000; 86: 1139-1141 Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar and device-related complications 2 Scholz K.H. Dubois-Rande J.L. Urban P. Morice M.C. Loisance D. Smalling R.W. Figulla H.R. Clinical experience with the percutaneous hemopump during high-risk coronary angioplasty. Am J Cardiol. 1998; 82: 1107-1110 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar , 4 Schreiber T.L. Kodali U.R. O’Neill W.W. Gangadharan V. Puchrowicz-Ochocki S.B. Grines C.L. Comparison of acute results of prophylactic intraaortic balloon pumping with cardiopulmonary support for percutaneous transluminal coronary angioplasty (PCTA). Cathet Cardiovasc Diagn. 1998; 45: 115-119 Crossref PubMed Scopus (22) Google Scholar , 7 Alderman J.D. Gabliani G.I. McCabe C.H. Brewer C.C. Lorell B.H. Pasternak R.C. Skillman J.J. Steer M.L. Baim D.S. Incidence and management of limb ischemia with percutaneous wire-guided intraaortic balloon catheters. J Am Coll Cardiol. 1987; 9: 524-530 Abstract Full Text PDF PubMed Scopus (87) Google Scholar have hampered a more widespread use of these methods. Recently, a newly developed percutaneous left ventricular assist device (pVAD) has been demonstrated to effectively reverse cardiogenic shock after myocardial infarction (Tandem Heart pVAD; Cardiac Assist Technologies, Inc., Ithaca, New York). 8 Thiele H. Lauer B. Hambrecht R. Boudriot E. Cohen H.A. Schuler G. Reversal of cardiogenic shock by percutaneous left atrial-to-femoral arterial bypass assistance. Circulation. 2001; 104: 2917-2922 Crossref PubMed Scopus (233) Google Scholar This system is readily deployed by percutaneous approach in the catheterization laboratory and is able to provide a systemic output of up to 4 L/min. An inflow cannula is inserted into the left atrium via transseptal puncture and the oxygenated blood is diverted to the femoral artery by a low-speed centrifugal continuous-flow pump. In this study, we report on a series of patients who underwent high-risk PCI supported by the Tandem Heart pVAD.

Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword?

Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of platelet aggregation that provide marked protection from ischemic events in patients undergoing percutaneous coronary intervention (PCI).1,2⇓ Abciximab, the prototypic GP IIb/IIIa inhibitor, has been studied in >8000 patients undergoing elective or high-risk PCI.2,3,4⇓⇓ In these patients, it produces a consistent 35% to 56% reduction in ischemic end points at 30 days, with a significant 22% reduction in the risk of death, as shown in a combined analysis of long-term (3-year minimum) follow-up of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG), and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials.5 Similar results, albeit of a smaller magnitude, have been seen with the small-molecule antagonists tirofiban and eptifibatide, with a 16% to 35% reduction in ischemic events in patients undergoing PCI.1,6⇓ Attempts to expand the therapeutic indication of GP IIb/IIIa antagonists to other conditions associated with platelet-mediated thrombosis, however, have been less fruitful than expected. Instead of reducing major ischemic events, long-term oral GP IIb/IIIa inhibitor therapy7 has uniformly increased the fatality rate. Furthermore, the overall efficacy of a number of the intravenous antagonists in non–ST-segment elevation acute coronary syndromes (ACS), or in combination with thrombolysis in ST-segment elevation myocardial infarction (MI), has been less than anticipated.8 Of particular concern is the fact that there has been a paradoxical increase in adverse events in 2 of the trials of intravenous therapy in ACS.9,10⇓ Platelets are known to play an important role in the pathogenesis of ACS, yet the high levels of platelet inhibition attainable with GP IIb/IIIa antagonists have failed to dramatically improve clinical outcomes outside of PCI. In this article, we discuss these …

Effect of metoprolol on absolute myocardial blood flow in patients with heart failure secondary to ischemic or nonischemic cardiomyopathy

F, Berger P, Popma J, Dangas G, et al. Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention. Results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation 2001;103:2572–2578. 2. Smith J, Steinhubl S, Lincoff A, Coleman J, Lee T, Hillman R, Coller B. The rapid platelet function assay: an automated and quantitative cartridge-based method. Circulation 1999;99:620–625. 3. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994;330:956–961. 4. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997;336:1689–1696. 5. The EPISTENT Investigators. Randomised placebo-controlled and balloonangioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. The EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1998;352:87–92. 6. Chew D, Bhatt D, Lincoff A, Moliterno D, Brener B, Wolski K, Topol E. Defining the optimal activated clotting time during percutaneous coronary intervention—aggregate results from 6 randomized, controlled trials. Circulation 2001;103:961–966.

Safety of abciximab during percutaneous coronary intervention in patients with chronic renal insufficiency

Despite numerous technical advances in recent years, percutaneous coronary intervention (PCI) in patients with chronic renal insufficiency is associated with poor long-term outcome compared with the general population. 1 Ting H.H. Tahirkheli N.K. Berger P.B. McCarthy J.T. Timimi F.K. Mathew V. Rihal C.S. Hasdai D. Holmes Jr, D.R. Evaluation of long-term survival after successful percutaneous coronary intervention among patients with chronic renal failure. Am J Cardiol. 2001; 87: 630-633 Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar The inhibition of the final common pathway of platelet aggregation by glycoprotein IIb/IIIa inhibitors during PCI has been shown to significantly reduce short- and long-term adverse cardiovascular end points in multiple studies. 2 The EPIC InvestigatorsUse of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation. N Engl J Med. 1994; 330: 956-961 Crossref PubMed Scopus (2675) Google Scholar , 3 The EPILOG InvestigatorsPlatelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med. 1997; 336: 1689-1696 Crossref PubMed Scopus (1968) Google Scholar , 4 IMPACT-II InvestigatorsRandomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Lancet. 1997; 349: 1422-1428 Abstract Full Text Full Text PDF PubMed Scopus (872) Google Scholar , 5 The EPISTENT InvestigatorsRandomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein- IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet. 1998; 352: 87-92 Crossref PubMed Google Scholar Patients with impaired renal function were excluded from most trials using glycoprotein IIb/IIIa inhibitors because there is concern about increased bleeding risk in this patient population. Therefore, the safety and efficacy of glycoprotein IIb/IIIa inhibitors in patients with chronic renal insufficiency is not well established. The present study evaluates bleeding risk and assesses the impact of abciximab therapy on outcome in patients with chronic renal insufficiency who underwent PCI.

Suboptimal early inhibition of platelets by treatment with tirofiban and implications for coronary interventions

We have found that platelet reactivity determined with the use of flow cytometry immediately before percutaneous coronary intervention (PCI) differentiates patients at high and low risk of adverse cardiac events after the procedure. 1 Kabbani S.S. Watkins M.W. Ashikaga T. Terrien E.F. Holoch P.A. Sobel B.E. Schneider D.J. Platelet reactivity characterized prospectively a determinant of outcome 90 days after percutaneous coronary intervention. Circulation. 2001; 104: 181-186 Crossref PubMed Scopus (141) Google Scholar Suppression of platelet aggregation by treatment with inhibitors of glycoprotein (GP) IIb/IIIa reduces the incidence of adverse cardiac events after PCI. 2 The EPIC InvestigatorsUse of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation. N Engl J Med. 1994; 330: 956-961 Crossref PubMed Scopus (2675) Google Scholar , 3 The EPILOG InvestigatorsPlatelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous revascularization. N Engl J Med. 1997; 336: 1689-1696 Crossref PubMed Scopus (1968) Google Scholar , 4 Tcheng J.E. Harrington R.A. Kottke-Marchant K. Kleiman N.S. Ellis S.G. Kereiakes D.J. Mick M.J. Navetta F.I. Smith J.E. Worley S.J. et al. Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators. Circulation. 1995; 91: 2151-2157 Crossref PubMed Scopus (276) Google Scholar , 5 IMPACT-II InvestigatorsRandomised placebo-controlled trial of the effect of integrilin on complications of PTCA IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Lancet. 1997; 349: 1422-1428 Abstract Full Text Full Text PDF PubMed Scopus (872) Google Scholar , 6 Kereiakes D.J. Kleiman N.S. Ambrose J. Chen M. Rodriquez S. Palabrica T. Herrmann H.C. Sutton J.M. Weaver W.D. McKee D.B. Fitzpatrick V. Sax F.L. Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol. 1996; 27: 536-542 Abstract Full Text PDF PubMed Scopus (205) Google Scholar , 7 The RESTORE InvestigatorsEffects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation. 1997; 96: 1445-1453 Crossref PubMed Google Scholar , 8 O’Shea J.C. Hafley G.E. Greenberg S. Hasselblad V. Lorenz T.J. Kitt M.M. Strony J. Tcheng J.E. ESPRIT InvestigatorsPlatelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial a randomized controlled trial. JAMA. 2001; 285: 2468-2473 Crossref PubMed Scopus (244) Google Scholar , 9 Topol E.J. Moliterno D.J. Herrmann H.C. Powers E.R. Grines C.L. Cohen D.J. Cohen E.A. Bertrand M. Neumann F.J. Stone G.W. DiBattiste P.M. Demopoulos L. TARGET InvestigatorsComparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med. 2001; 344: 1888-1894 Crossref PubMed Scopus (706) Google Scholar In the Do Tirofiban And Reo Pro Give similar Efficacy outcome Trial (TARGET), a lower 30-day incidence of the combined end point of death, myocardial infarction, and urgent target vessel revascularization was seen in patients treated with abciximab compared with those who received tirofiban. 9 Topol E.J. Moliterno D.J. Herrmann H.C. Powers E.R. Grines C.L. Cohen D.J. Cohen E.A. Bertrand M. Neumann F.J. Stone G.W. DiBattiste P.M. Demopoulos L. TARGET InvestigatorsComparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med. 2001; 344: 1888-1894 Crossref PubMed Scopus (706) Google Scholar The present study was designed to determine whether the difference observed reflected suboptimal inhibition of platelet aggregation during the first 2 hours after initiation of treatment with tirofiban. We focused on this interval because our previous investigation has suggested that the extent of inhibition with the 2 agents was similar 6 to 10 hours after initiation of therapy. 10 Holmes M.B. Kabbani S.S. Terrien C.M. Watkins M.W. Sobel B.E. Schneider D.J. Quantification by flow cytometry of the efficacy of and interindividual variation of platelet inhibition induced by treatment with tirofiban and abciximab. Coron Artery Dis. 2001; 12: 245-253 Crossref PubMed Scopus (19) Google Scholar CorrectionAmerican Journal of CardiologyVol. 89Issue 12Preview Full-Text PDF

Safety, inhibition of platelet aggregation and pharmacokinetics of F(ab′) 2 fragments of the anti-glycoprotein IIb-IIIa monoclonal antibody FRaMon in high-risk coronary angioplasty

The purpose of the study was to evaluate safety, effects on platelet aggregation and pharmacokinetics of F(ab') 2 fragments of anti-glycoprotein (GP) IIb-IIIa murine monoclonal antibody FRaMon (F(ab') 2 FRaMon) upon its intravenous administration in patients undergoing high-risk coronary angioplasty. Patients were treated before angioplasty with F(ab') 2 FRaMon at 0.2 mg/kg ( n = 17) and 0.25 mg/kg ( n = 12) bolus or with abciximab at 0.25 mg/kg bolus + 12 h infusion at 0.125 w g/kg per min ( n = 29). F(ab') 2 FRaMon at both doses decreased platelet aggregation induced by 20 w M ADP to <10, <20, <40 and <70% of the predrug level at 1, 12, 24 and 72 h after injection, respectively. No significant differences were observed between F(ab') 2 FRaMon and abciximab antiaggregatory effects. In none of the patients did F(ab') 2 FRaMon cause allergic reactions, major bleedings or deep thrombocytopenia. Antibodies against F(ab') 2 FRaMon were detected in one patient. Free F(ab') 2 FRaMon was cleared from plasma within 12 h, while platelet-bound preparation occupied >95, 70-80 and 40-50% of GP IIb-IIIa at 1 and 12-24 h and 3 days after injection, respectively. Thrombotic complications within the first month after angioplasty in groups treated with F(ab') 2 FRaMon and abciximab were observed in one and two patients, respectively. The data obtained have shown that F(ab') 2 FRaMon at bolus administration to patients undergoing coronary angioplasty caused no serious side effects and at comparative dosage inhibited platelet aggregation with the same efficacy as abciximab at bolus + infusion administration.