Background Platelets are believed to play a part in the ischemiccomplications of coronary angioplasty, such as abrupt closureof the coronary vessel during or soon after the procedure. Accordingly,we evaluated the effect of a chimeric monoclonal-antibody Fabfragment (c7E3 Fab) directed against the platelet glycoproteinIIb/IIIa receptor, in patients undergoing angioplasty who wereat high risk for ischemic complications. This receptor is thefinal common pathway for platelet aggregation.
Methods In a prospective, randomized, double-blind trial, 2099patients treated at 56 centers received a bolus and an infusionof placebo, a bolus of c7E3 Fab and an infusion of placebo,or a bolus and an infusion of c7E3 Fab. They were scheduledto undergo coronary angioplasty or atherectomy in high-riskclinical situations involving severe unstable angina, evolvingacute myocardial infarction, or high-risk coronary morphologiccharacteristics. The primary study end point consisted of anyof the following: death, nonfatal myocardial infarction, unplannedsurgical revascularization, unplanned repeat percutaneous procedure,unplanned implantation of a coronary stent, or insertion ofan intraaortic balloon pump for refractory ischemia. The numbersof end-point events were tabulated for 30 days after randomization.
Results As compared with placebo, the c7E3 Fab bolus and infusionresulted in a 35 percent reduction in the rate of the primaryend point (12.8 vs. 8.3 percent, P = 0.008), whereas a 10 percentreduction was observed with the c7E3 Fab bolus alone (12.8 vs.11.5 percent, P = 0.43). The reduction in the number of eventswith the c7E3 Fab bolus and infusion was consistent across theend points of unplanned revascularization procedures and nonfatalmyocardial infarction. Bleeding episodes and transfusions weremore frequent in the group given the c7E3 Fab bolus and infusionthan in the other two groups.
Conclusions Ischemic complications of coronary angioplasty andatherectomy were reduced with a monoclonal antibody directedagainst the platelet IIb/IIIa glycoprotein receptor, althoughthe risk of bleeding was increased.
Percutaneous coronary angioplasty is associated with improvementin the symptoms of ischemia and the quality of life,1,2 butacute complications remain a major drawback. The treated vesselcloses abruptly during or soon after the procedure in 4 to 9percent of cases, causing considerable morbidity and an approximately10-fold increase in mortality3,4,5,6,7. Characteristics thatidentify patients at high risk for acute complications includethe presence of a clinical syndrome associated with coronarythrombus (such as unstable angina or recent myocardial infarction),diabetes, female sex, and complex coronary morphologic features(an angulated arterial segment, thrombus, or bifurcation lesion)3,7,8,9,10.
Although aspirin reduces the risk of abrupt vessel closure andacute myocardial infarction in patients undergoing angioplasty,11,12its effects on platelet function are relatively weak, and ischemicevents continue to occur in 10 to 20 percent of patients athigh risk who have been treated with aspirin8. The integringlycoprotein IIb/IIIa receptor on the surface of the platelet,the final common pathway of platelet aggregation,13 binds circulatingadhesive macromolecules, particularly fibrinogen and von Willebrandfactor, which can then cross-link receptors on adjacent platelets,leading to platelet aggregation.
In 1985 Coller produced a mouse monoclonal antibody, known as7E3, against this platelet receptor,14 and its antithromboticeffects were demonstrated in animal models15. In pilot studiesin patients16 this agent inhibited platelet aggregation by morethan 80 percent, thus showing its promising biologic and clinicaleffects. The current study was designed to determine whetherthe biologic properties of c7E3 Fab would translate into clinicalbenefit in the setting of coronary angioplasty or atherectomy.
Methods
Study Population
Patients scheduled to undergo coronary angioplasty or directionalatherectomy were eligible for enrollment if they were at highrisk for abrupt vessel closure and were not at high risk forbleeding. They were considered to be at high risk for vesselclosure if they had one of three clinical features: (1) acuteevolving myocardial infarction within 12 hours after the onsetof symptoms that necessitated direct or "rescue" percutaneousintervention; (2) early postinfarction angina or unstable anginawith at least two episodes of angina at rest associated withchanges on resting electrocardiography during the previous 24hours, despite medical therapy; or (3) clinical or angiographiccharacteristics indicating high risk, according to the criteriaof the American Heart Association and the American College ofCardiology17 as modified by Ellis et al.7. Patients were excludedif they were 80 years old or older, were known to have a bleedingdiathesis, had undergone major surgery within the precedingsix weeks, or had had a stroke within the preceding two years.Approval was obtained from the institutional review board ofeach study center, and informed consent from each patient. Patientswere recruited between November 1991 and November 1992; 2099patients were enrolled at 56 institutions in the United States(see the Appendix).
Study Protocol
All the patients were treated with aspirin and heparin. Aspirinwas administered orally in a dose of 325 mg at least two hoursbefore angioplasty or atherectomy and daily thereafter. Heparinwas given intravenously in an initial bolus dose of 10,000 to12,000 units followed by incremental bolus doses of up to 3000units at 15-minute intervals, but no more than 20,000 unitswas given during the procedure; the goal was to keep the activatedclotting time between 300 and 350 seconds during the operation18,19,20.Heparin was continued by constant infusion for at least 12 hoursto maintain the activated partial-thromboplastin time at 1.5to 2.5 times the control value. The only medication requiredat discharge was aspirin in a dose of 325 mg per day. The chimeric7E3 Fab (Centocor, Malvern, Pa.) used in the study is a Fabfragment of a human-mouse genetic reconstruction of a murinemonoclonal IgG molecule that binds selectively to the glycoproteinIIb/IIIa platelet receptor. It was supplied as a sterile, nonpyrogenicsolution containing 2 mg of monoclonal Fab per milliliter of0.15 M sodium chloride, 0.01 M sodium phosphate, and 0.001 percentpolysorbate 80 (pH 7.2).
Patients were randomly assigned to one of the following threetreatment groups according to a double-blind study design: c7E3Fab in a bolus dose of 0.25 mg per kilogram of body weight,followed by an infusion of 10 µg per minute; c7E3 Fabin a bolus dose of 0.25 mg per kilogram, followed by a placeboinfusion; or a placebo bolus and a placebo infusion. The bolusdose was started at least 10 minutes before the procedure andgiven over a 5-minute period, and the infusion was continuedfor 12 hours unless a clinical contraindication developed.
Blood samples were obtained 30 minutes and 2, 12, and 24 hoursafter treatment began and then daily until hospital dischargeand were carefully examined for evidence of thrombocytopenia.A predesigned algorithm was used to evaluate and treat life-threateningbleeding and thrombocytopenia,21 although no specific hemoglobinvalue was used to determine whether red-cell transfusions shouldbe given. Vascular sheaths were maintained for at least sixhours after the end of the infusion of the study drug and wereleft in place at least four hours after the end of the heparininfusion and until an acceptable activated partial-thromboplastintime was achieved to maintain hemostasis.
Study End Points
The primary end point of the trial was a prespecified compositeof any of the following events in the first 30 days after randomization:death from any cause, nonfatal myocardial infarction, coronary-arterybypass grafting or repeat percutaneous intervention for acuteischemia, and insertion of a coronary endovascular stent becauseof procedural failure or placement of an intraaortic counterpulsationballoon pump to relieve refractory ischemia. Events were classifiedby the consensus of at least two members of an independent clinical-end-pointscommittee blinded to the patients' treatment groups throughoutthe study.
If a patient entered the trial within 24 hours after an acuteevolving myocardial infarction, one of two enzymatic criteriawas required for the diagnosis of a subsequent nonfatal infarction:the activity of creatine kinase or its MB isozyme had to beat least three times the upper limit of normal, representingan increase of at least 33 percent from the previous "valley"(defined as a 25 percent decrease from a previous peak valuebut remaining at least twice the upper limit of normal); orthe activity of creatine kinase or the MB isozyme increasedby at least 100 percent and remained three times the upper limitof normal after a 50 percent decrease from a previous peak leveland a valley level less than twice the upper limit of normal.The MB isozyme value was used (in more than 95 percent of patients)unless it was not available, in which case the value for totalcreatine kinase was used.
If a patient entered the trial more than 24 hours after an acuteinfarction or without a recent infarction, one of two criteriahad to be met for a diagnosis of in-hospital myocardial infarction:a new Q wave with a duration of at least 0.04 second or a depthof more than one fourth the amplitude of the corresponding Rwave in two or more contiguous leads; or an MB isozyme levelmore than three times the upper limit of normal, representingan increase of 50 percent or more over the previous valley level.After hospital discharge, either a new Q wave with the sameadverse characteristics or a creatine kinase or MB isozyme levelmore than twice the upper limit of normal was required.
Other components of the primary end point were an unplannedrepeat angioplasty to treat recurrent ischemia, urgent coronarysurgery to treat recurrent ischemia or failure of an angioplasty,placement of an intracoronary stent to treat imminent or completeabrupt closure of the vessel undergoing angioplasty, and placementof an intraaortic balloon pump for recurrent ischemia when arepeat revascularization procedure was contraindicated.
Bleeding events were classified as major, minor, or insignificantaccording to the criteria of the Thrombolysis in MyocardialInfarction Study Group22. To estimate the total number of unitsof blood lost in patients who received blood transfusions, thenumber of units transfused was added to the observed drop inthe hematocrit divided by 323.
Data Management and Statistical Analysis
After randomization by telephone, the patients were stratifiedaccording to their study center and whether they were havingan acute evolving myocardial infarction. On the basis of datafrom previous trials, this trial was planned to include 2100patients to detect a reduction of 33 percent in the primaryend point (the event rate in the placebo group was predictedto be 15 percent), with a power of 0.8 and an alpha level of0.05.
Data were collected by study coordinators on case-report formsand monitored by blinded study monitors before data entry. Thetrial sponsor (Centocor) and the investigators remained blindedto the randomization code and study results until all end pointshad been agreed on by the clinical-end-points committee andall details of the analysis plan were finalized.
The primary end point of the trial was analyzed by evaluatingthe time to the first occurrence of any one of the componentsof the composite end point that occurred within the first 30days after enrollment. The results in the three treatment groupswere displayed as Kaplan-Meier survival curves24 and comparedaccording to the intention-to-treat principle. For the primaryend point, a log-rank test for trend was performed in whichthe group assigned to the bolus of c7E3 Fab ranked between thegroup assigned to both the bolus and infusion of c7E3 Fab andthe group given only placebo25. The analysis plan then calledfor pairwise log-rank comparisons between the placebo groupand each of the two c7E3 Fab groups if the result of the testfor trend was significant. Interim analyses were performed whendata were available for one third and approximately two thirdsof the patients. The nominal alpha level used for judging thesignificance of the test for trend and the pairwise group comparisonsat each interim analysis was prespecified to maintain an overalltype I error rate of 0.05. In the final analysis, the levelof significance used in comparisons of the primary end pointwas 0.036. Differences among the treatment groups with respectto each component of the composite end point were also examinedin the final analysis, although these comparisons were madefor explanatory purposes. The data were presented with nominaltwo-tailed P values (unadjusted for multiple comparisons); readerscan therefore make appropriate adjustments for multiplicitywhen interpreting the results. The prespecified final analysisalso compared the treatment groups with respect to measuresof bleeding complications, using conventional chi-square testing.Odds ratios and confidence intervals for the treatment effectin major subgroups (classified according to sex, age, weight,and clinical features at entry) were calculated, with the primaryoutcome used as a binary end point.
Results
There were no substantial differences among the treatment groupsin their base-line clinical characteristics (Table 1). Whenthe c7E3 Fab groups were compared with the placebo group, agraded effect of c7E3 Fab was found (P = 0.009), with a 10 percentreduction in the rate of the composite end point in the groupgiven the c7E3 Fab bolus alone (P = 0.43) and a 35 percent reductionin the rate in the group given both this bolus and the infusion(P = 0.008) (Table 2). A similar graded effect was observedfor each of the most important individual end points relatingto ischemia, including the spectrum of nonfatal myocardial infarctions.Three of the deaths among the patients assigned to the c7E3Fab bolus and infusion occurred after randomization but beforedrug administration; these deaths were included in the analysisaccording to the intention-to-treat principle.
Table 1. Base-Line Characteristics and Procedures Performed in 2099 Patients at High Risk for Ischemia during Coronary Surgery, According to Treatment Group.
Table 2. Primary Outcome Events in the Treatment Groups.
The times of nonfatal ischemic events differed among the threegroups, as shown in Figure 1 for urgent repeat angioplasty,an event whose beginning and end could be determined accurately.In the placebo group, more ischemic events occurred during thefirst six hours after the procedure than later (P<0.03),whereas in the group given the c7E3 Fab bolus, events were delayedfor several hours, corresponding to the time of maximal receptorblockade. There was a marked delay in the onset of ischemicevents in the group given the c7E3 Fab bolus and infusion, aswell as a marked reduction in their absolute frequency.
Figure 1. Probability of No Urgent Repeated Percutaneous Revascularization Procedures in the Three Treatment Groups (Kaplan-Meier Plots).
Events began to occur shortly after the index procedure in the placebo group, between 6 and 12 hours after the procedure in the group given the bolus of c7E3 Fab, and even later in the group given both the bolus and the infusion. The y axis is truncated at 97 percent to demonstrate the differences in this end point, which occurred with low frequency.
The rates of bleeding complications during hospitalization areshown in Table 3. The group given the c7E3 Fab bolus and infusionhad a substantial increase in both the rate of major bleedingand that of transfusion, with a more moderate increase seenin the group given the bolus alone. The majority of bleedingepisodes occurred during coronary-artery bypass grafting orat the site of vascular puncture in the groin. The rates ofsurgery for bleeding were similar (1.4 percent in the placebogroup, 2.6 percent in the group given the c7E3 Fab bolus only,and 1.7 percent in the group given both the bolus and the infusion).Similarly, six patients had an intracranial hemorrhage -- twopatients assigned to placebo only, one patient assigned to thec7E3 bolus, and three patients assigned to the bolus and infusion;one of these last three patients did not receive the drug becausethe hemorrhage occurred after randomization but before angioplasty.
Table 3. Bleeding Complications and Hematologic Values in the Treatment Groups.
When the treatment effect was evaluated in subgroups definedaccording to whether patients were enrolled with an acute ischemicsyndrome or unstable angina or with high-risk anatomical features,the odds ratio for the primary end point was less than 1.0 inall subgroups (Table 4). Similarly, the treatment effect washomogeneous across the subgroups defined by age and sex.
Table 4. Event Rates of Primary End Point and Transfusion in Subgroups Defined before Entry.
As a function of body weight, the hazard ratio for the primaryend point was less than 1.0 across the study population, althoughthe treatment effect was more pronounced in heavier patients.The risk of major bleeding was increased in lighter patientsgiven c7E3 Fab (whether the bolus only or both the bolus andthe infusion). In the lightest third of the patients, majorbleeding occurred in 21 percent of those given both the bolusand the infusion of c7E3 Fab, 15 percent of those given thebolus only, and 7 percent of those given placebo, whereas inthe heaviest third the corresponding rates of bleeding were9, 7, and 6 percent.
Discussion
This study confirms the importance of platelet aggregation inthe occurrence of acute ischemic events in patients undergoingpercutaneous transluminal coronary angioplasty26. The administrationof c7E3 Fab directed against the platelet glycoprotein IIb/IIIareceptor as a bolus and infusion resulted in a 35 percent reductionin the composite-event rate, primarily in the rate of nonfatalmyocardial infarction and the need for emergency angioplastyor bypass surgery. This beneficial effect was achieved at thecost of a significant increase in bleeding complications andtransfusions. Judgment about the clinical usefulness of thisapproach in patients at high risk for ischemic complicationsduring or after percutaneous revascularization depends on thevalue of averting ischemic events relative to the value of reducingthe need for blood products. In the high-risk patients enrolledin this trial, the balance appeared to be favorable.
The composite end point serves as an overall estimate of theeffect of this therapeutic approach on ischemic events in theperiod encompassing angioplasty. One of the most important findingsof this trial is the consistency in the reduction of eventsacross the various end points. This consistency is further demonstratedby the closeness of the hazard ratios across the range of patientcharacteristics in many subgroups (Table 4). Nominal statisticalsignificance for a treatment effect with regard to each endpoint or within each subgroup would not be expected in viewof the size of the study population27. Together with the positiveresults of a recent pilot trial in which the same antibody wasgiven to patients with refractory unstable angina,28 the beneficialeffect of glycoprotein IIb/ IIIa-receptor blockade on clinicalend points in the setting of high-risk angioplasty is convincing.
The classification of nonfatal myocardial infarction has becomea major issue in the evaluation of percutaneous coronary interventions.Elevations of creatine kinase MB isozyme activity above theupper limit of normal commonly occur in 4 to 21 percent of patients,29,30,31,32yet when they are not accompanied by discrete clinical events,their association with long-term adverse outcomes is not clear.Thus, preventing isolated enzyme elevations may not be prognosticallymeaningful. To ensure objectivity in this subtle area, we systematicallycollected enzyme values and electrocardiograms, set up a blindedend-point committee, and required at least a threefold increasein myocardium-specific enzyme activity to classify an eventas a myocardial infarction. Treatment with c7E3 Fab reducedall types of myocardial infarctions, including those associatedwith moderate and large enzyme elevations and Q-wave development,and also reduced the need for emergency coronary revascularization.
The blood loss observed in this trial was substantial and resultedin a significant increase in the use of blood products. Thedoubling of the transfusion rate in patients who received botha bolus and an infusion of c7E3 Fab occurred primarily as aresult of bleeding at the femoral puncture site and did notlead to a marked difference among the three treatment groupsin nadir hematocrits or the rate of life-threatening complications.The trends remained the same whether or not surgically treatedpatients were included in the analysis. Our previous experiencehas demonstrated that a refined protocol for the managementof bleeding and the administration of transfusions in patientsgiven thrombolytic therapy can effectively reduce the need forblood products33.
The relation between treatment benefit and the risk of bleedingas a function of body weight was more complex than expected.Although the primary-event rate and the risk of major bleedingdid not vary substantially with weight in the placebo groupin our study, it was clear that weight was inversely relatedto the number of primary-outcome events and major episodes ofbleeding in the group given the bolus and infusion of c7E3 Fab.Future studies and clinical practice using potent, parenterallyadministered antithrombotic agents in patients with indwellingtubes or catheters must focus on weight-adjusted dosing withantithrombotic drugs, more detailed evaluation of the mechanismsby which antithrombotic therapy prevents ischemic complications,and protocols that define approaches to reduce bleeding thatwill be applied consistently at all participating centers.
These findings have many implications for future scientificinquiry. The broad consistency of the treatment effect acrossthe study population is strong evidence that platelet thrombosisplays an important part in the abrupt closure of coronary lesionstreated by angioplasty. The apparent delay of adverse eventsby the bolus of c7E3 Fab and the prevention of events by thebolus and infusion imply that in most situations the surfaceof the disrupted artery has lost much of its thrombogenicity18 to 24 hours after the procedure. This finding suggests thatfu-ture therapies must take into account the need for sustainingan antithrombotic effect in patients at high risk for abruptvessel closure.
In summary, this trial demonstrates a beneficial effect of substantialand sustained blockade of the glycoprotein IIb/IIIa receptorin patients undergoing high-risk percutaneous revascularizationprocedures, although this benefit was achieved at the risk ofincreased bleeding. The relative value of a reduction in ischemicevents as compared with an increase in bleeding events is atthe crux of the decision about the clinical usefulness of glycoproteinIIb/IIIa-receptor blockade. Previous surveys of cardiologists'attitudes and clinical practice have demonstrated that theygenerally regard the transfusion of blood products as a muchless serious clinical event than either an acute myocardialinfarction or emergency repeat revascularization34. The prognosticimplications of either of the latter two adverse events areserious, and fortunately the risks associated with transfusioncontinue to decline35,36,37. Future efforts to employ practicealgorithms to avert bleeding and transfusions and to determinedoses of antithrombotic agents more effectively, including theirantithrombin and antiplatelet effects, should further enhancethe clinical benefits observed in this trial.
Supported by a grant from Centocor, Inc., Malvern, Pa.
Source Information
From the Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, N.C. Dr. Califf, as the corresponding author, assumes overall responsibility for the contents of the manuscript.The principal investigators and study coordinators of the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) Study Group are listed in the Appendix.
Address reprint requests to Dr. Robert M. Califf at Box 31123, Duke University Medical Center, Durham, NC 27710.
References
Gruentzig AR, King SB III, Schlumpf M, Siegenthaler W. Long-term follow-up after percutaneous transluminal coronary angioplasty: the early Zurich experience. N Engl J Med 1987;316:1127-1132. [Abstract]
Parisi AF, Folland ED, Hartigan P. A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. N Engl J Med 1992;326:10-16. [Abstract]
Tenaglia AN, Fortin DF, Frid DJ, et al. Long-term outcome following successful reopening of abrupt closure after coronary angioplasty. Am J Cardiol 1993;72:21-25. [CrossRef][Medline]
Detre KM, Holmes DR Jr, Holubkov R, et al. Incidence and consequences of periprocedural occlusion: the 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation 1990;82:739-750. [Free Full Text]
Ellis SG, Roubin GS, King SB III, et al. Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 1988;77:372-379. [Free Full Text]
Ellis SG, Bates ER, Schaible T, Weisman HF, Pitt B, Topol EJ. Prospects for the use of antagonists to the platelet glycoprotein IIb/IIIa receptor to prevent post-angioplasty restenosis and thrombosis. J Am Coll Cardiol 1991;17:Suppl B:89B-95B.
Tenaglia AM, Fortin DF, Frid DJ, et al. Individualizing the risk of angioplasty abrupt vessel closure. J Am Coll Cardiol (in press).
Moushmoush B, Kramer B, Hsieh AM, Klein LW. Does the AHA/ACC task force grading system predict outcome in multivessel coronary angioplasty? Cathet Cardiovasc Diagn 1992;27:97-105. [Medline]
Myler RK, Shaw RE, Stertzer SH, et al. Unstable angina and coronary angioplasty. Circulation 1990;82:Suppl II:II-88.
Schwartz L, Bourassa MG, Lesperance J, et al. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988;318:1714-1719. [Abstract]
Barnathan ES, Schwartz JS, Taylor L, et al. Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty. Circulation 1987;76:125-134. [Free Full Text]
Harker LA. Role of platelets and thrombosis in mechanisms of acute occlusion and restenosis after angioplasty. Am J Cardiol 1987;60:Suppl:20B-28B. [Medline]
Coller BS. A new murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet glycoprotein IIb/IIIa complex. J Clin Invest 1985;76:101-108.
Coller BS, Scudder LR. Inhibition of dog platelet function by in vivo infusion of F(ab')2 fragments of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor. Blood 1985;66:1456-1459. [Free Full Text]
Ellis SG, Navetta FI, Tcheng JT, et al. Safety and antiplatelet effect of murine monoclonal antibody 7E3 Fab directed against platelet glycoprotein IIb/IIIa in patients undergoing elective coronary angioplasty: an initial experience. Coron Artery Dis 1993;4:167-175. [Medline]
Ryan TJ, Faxon DP, Gunnar RM, et al. Guidelines for percutaneous transluminal coronary angioplasty: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1988;78:486-502. [Free Full Text]
Dougherty KG, Marsh KC, Edelman SK, Gaos CM, Ferguson JJ, Leachman DR. Relationship between procedural activated clotting time and in-hospital post-PTCA outcome. Circulation 1990;82:Suppl IV:IV-189.
Rath B, Bennett DH. Monitoring the effect of heparin by measurement of activated clotting time during and after percutaneous transluminal coronary angioplasty. Br Heart J 1990;63:18-21. [Free Full Text]
Ogilby JD, Kopelman HA, Klein LW, Agarwal JB. Adequate heparinization during PTCA: assessment using activated clotting times. Cathet Cardiovasc Diagn 1989;18:206-209. [Medline]
Sane DC, Califf RM, Topol EJ, Stump DC, Mark DB, Greenberg CS. Bleeding during thrombolytic therapy for acute myocardial infarction: mechanisms and management. Ann Intern Med 1989;111:1010-1022.
Rao AK, Pratt C, Berke A, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial -- phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988;11:1-11. [Abstract]
Landefeld CS, Cook EF, Flatley M, Weisberg M, Goldman L. Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med 1987;82:703-713. [CrossRef][Medline]
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: John Wiley, 1980.
Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM. Specific platelet mediators and unstable coronary artery lesions: experimental evidence and potential clinical implications. Circulation 1989;80:198-205. [Free Full Text]
Yusuf S, Wittes J, Probstfield J, Tyroler HA. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA 1991;266:93-98. [Free Full Text]
Simoons ML, de Boer MJ, van den Brand MJBM, et al. Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. Circulation 1994;89:596-603. [Free Full Text]
Klein LW, Kramer BL, Howard E, Lesch M. Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty. J Am Coll Cardiol 1991;17:621-626. [Abstract]
Hunt AC, Chow SL, Shiu MF, Chilton DC, Cummins B, Cummins P. Release of creatine kinase-MB and cardiac specific troponin-I following percutaneous transluminal coronary angioplasty. Eur Heart J 1991;12:690-693.
Pauletto P, Piccolo D, Scannapieco G, et al. Changes in myoglobin, creatine kinase and creatine kinase-MB after percutaneous transluminal coronary angioplasty for stable angina pectoris. Am J Cardiol 1987;59:999-1000. [CrossRef][Medline]
Spadaro JJ, Ludbrook PA, Tiefenbrunn AJ, Kurnik PB, Jaffe AS. Paucity of subtle myocardial injury after angioplasty delineated with MB CK. Cathet Cardiovasc Diagn 1986;12:230-234. [Medline]
Wall TC, Califf RM, Ellis SG, et al. Lack of impact of early catheterization and fibrin specificity on bleeding complications after thrombolytic therapy. J Am Coll Cardiol 1993;21:597-603. [Abstract]
Califf RM, Harrelson-Woodlief L, Topol EJ. Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials. Circulation 1990;82:1847-1853. [Free Full Text]
Donahue JG, Munoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med 1992;327:369-373. [Abstract]
Dodd RY. The risk of transfusion-transmitted infection. N Engl J Med 1992;327:419-421. [Medline]
Nelson KE, Donahue JG, Munoz A, et al. Transmission of retroviruses from seronegative donors by transfusion during cardiac surgery: a multicenter study of HIV-1 and HTLV-I/II infections. Ann Intern Med 1992;117:554-559.
Appendix
The following are the principal investigators and study coordinatorsof the EPIC Study Group: Presbyterian Hospital, Albuquerque,N.M. -- N. Shadoff and N. Valett; University of Michigan MedicalCenter, Ann Arbor -- E. Bates and A. Galeana; St. Joseph Hospital,Atlanta -- W. Knopf, J. Shaftel, and M.J. Bender; Johns HopkinsHospital, Baltimore -- T. Aversano and J. Raqueno; Universityof Maryland Hospital, Baltimore -- P. Gurbel and J. Cowfer;St. Francis Hospital, Beech Grove, Ind. -- M. Cohen and P. Cross;Brigham and Women's Hospital, Boston -- J. Bittl and K. Eddings;Deborah Heart Center, Brown Mill, N.J. -- M. Taylor and K. DeRosa;DePaul Hospital, Cheyenne, Wyo. -- L. Hattel, L. Cooper, andB. Eshelman; Northwestern University, Chicago -- D. Fintel andP. Niemyski; Rush-Presbyterian-St. Luke's Medical Center, Chicago-- L. Klein, H. Kennedy, and T. Thornton; Christ Hospital, Cincinnati-- D. Kereiakes, L. Martin, L. Anderson, and N. Higby; ClevelandClinic, Cleveland -- S. Ellis and K. Brezina; Riverside MethodistHospitals, Columbus, Ohio -- B. George, A. Chapekis, and D.Smith; Baylor University, Dallas -- A. Anwar, T.L. Gerber, andG.L. Pritchard; San Francisco Heart Institute, Daly City, Calif.-- R. Myler, R. Shaw, M. Murphy, and K. Ward; Geisinger MedicalCenter, Danville, Pa. -- N.P. Madigan, J. Blankenship, M. Halbert,and C. Flanagan; Iowa Heart Center Mercy Hospital, Des Moines-- M. Tannenbaum, M. Polich, and C. Stevenson; Duke University,Durham, N.C. -- J. Tcheng, S. Hoffman, and R.M. Moore; St.Vincent Health Center, Erie, Pa. -- J. Smith and P. Henry; EvanstonHospital, Evanston, Ill. -- T.J. McDonough and S. Weszt; MosesCone Hospital, Greensboro, N.C. -- B. Brodie and D. Muncy;Baylor University Methodist/Ben Taub General Hospital, Houston-- N. Kleiman, K. Trainor, D. Rose, and S. Johnson; Texas HeartInstitute, Houston -- J. Willerson, J.J. Ferguson, and M. Harlan;University of Florida Medical Center, Jacksonville -- T.A. Bassand G. Rohman; Lakeland General Hospital, Lakeland, Fla. --K. Browne and C. Ciesla; Lancaster General Hospital, Lancaster,Pa. -- S. Worley and J. Tuzi; Dartmouth-Hitchcock Medical Center,Lebanon, N.H. -- B. Hettleman, W.C. Burke, G. Olsen, and S.J.Kennedy; University of Louisville, Louisville, Ky. -- J.D. Talley,Z.A. Yussman, and M. Rawert; Loyola University Hospital, Maywood,Ill. -- E.D. Grassman and L. Wrona; Baptist Memorial, Memphis,Tenn. -- J. Samaha and B. Ehemann; East Jefferson Hospital,Metairie, La. -- S.D. Bleich and R. Leonhard; St. Luke's MedicalCenter, Milwaukee -- F. Cummins and J. Nonnweiler; St. PatrickHospital, Missoula, Mont. -- M. Sanz and D. Mayer; Yale UniversityMedical Center, New Haven, Conn. -- M.W. Cleman, V.J. Pascale,and S. McConnell; Creighton University Cardiac Center, Omaha,Nebr. -- M. Del Core and L. Stengel; Florida Hospital, Orlando,Fla. -- R.J. Ivanhoe and N. Granger; Lutheran General Hospital,Park Ridge, Ill. -- M.J. Rosenberg and A. Schaechter; SacredHeart, Pensacola, Fla. -- G. Aycock and T. Wilcox; GraduateHospital, Philadelphia -- R. Gottlieb and H. Hunter; PhiladelphiaHeart Institute, Philadelphia -- W. Unterecker and B. Hart;Arizona Heart Institute and Foundation, Phoenix -- R. Heuserand S. Hoopmann; North Memorial Medical Center, Robbinsdale,Minn. -- G. Hanovich and A. Antolick; Rochester General Hospital,Rochester, N.Y. -- G. Gacioch, V. Chiodo, and K. Karski; WilliamBeaumont Hospital, Royal Oak, Mich. -- G. Timmis and M. Safian;St. Louis University, St. Louis -- F. Aguirre and T. Stonner;St. John's Hospital, Springfield, Ill. -- G.J. Taylor, K. Womack,and B. Ruyle; South Miami Hospital, Miami -- D. Krauthamer andG. Welcom; Tampa General Hospital, Tampa, Fla. -- M. Westonand K. Dillon; Harbor-UCLA Medical Center, Torrance, Calif.-- W.J. French and G.T. Reynolds; Mother Frances Hospital,Tyler, Tex. -- F. Navetta, G. Murphy, R. LeBoeuf, and S. Spencer;and Washington Hospital Center, Washington, D.C. -- J.J. Popmaand L. Sweet.
Executive Committee -- E.J. Topol, R.M. Califf, C.R. Smith,H. Weisman, and K.L. Lee; Coordinating Center -- J. Miller,K. Sigmon, R.M. Califf, J. Tcheng, K.L. Lee, M. Lui, A. Kosloff,and J. DiFulvio (Durham, N.C.); and A.L. Wang, K. Anderson,H. Weisman, R. Dann, W. Kingma, D. Norton, B. Myer, R. Masek,M. Lewandowski, S. Broderick, M. Musco, M. Schorr, P. Hartman,and L. McCardle (Malvern, Pa.); Safety Data Monitoring Committee-- D. Faxon (chairman), P. Armstrong, J. Gore, J. Loscalzo,L. McCullough, and J. Verter; Economics and Quality of Life-- D.B. Mark, L. Davidson-Ray, N. Clapp-Channing, and L.C. Lam;Clinical Events Committee -- R.A. Waugh (chairman), C.B. McCants,Jr., M.C. Hindman, G. Dehmer, W.B. Hillegass, D.J. Frid, D.F.Fortin, B.C. Brott, T.L. Forest, D.M. Unks, and M.E. Hamer;ECG Core Laboratory -- G.S. Wagner and K. Gates; and ThrombocytopeniaCore Laboratory -- D. Sane.
Tanzilli, G., Sordi, M., Arrivi, A., Mangieri, E., Scappaticci, M.
(2009). Acute profound abciximab induced thrombocytopenia: a correct management of a methodological error. BMJ Case Reports
2009: bcr1220081381-bcr1220081381
[Abstract][Full Text]
Hetherington, S L, Adam, Z, Morley, R, de Belder, M A, Hall, J A, Muir, D F, Sutton, A G C, Swanson, N, Wright, R A
(2009). Primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: changing patterns of vascular access, radial versus femoral artery. Heart
95: 1612-1618
[Abstract][Full Text]
Nishimura, S. L.
(2009). Integrin-Mediated Transforming Growth Factor-{beta} Activation, a Potential Therapeutic Target in Fibrogenic Disorders. Am. J. Pathol.
175: 1362-1370
[Abstract][Full Text]
Damman, P., Tijssen, J., de Winter, R., Rathod, B., Cequier, A., Gomez-Hospital, J. A., Gonzalez-Costello, J., Shojai, S., Mehta, S. R., Yusuf, S., Granger, C., Hillis, L. D., Lange, R. A.
(2009). Acute Coronary Syndromes. NEJM
361: 925-927
[Full Text]
Pogue, J., Walter, S. D, Yusuf, S.
(2009). Evaluating the benefit of event adjudication of cardiovascular outcomes in large simple RCTs. Clin Trials
6: 239-251
[Abstract]
Denardo, S. J.
(2009). Exclusive Antiplatelet Therapy for Percutaneous Coronary Intervention. J Am Coll Cardiol
53: 1921-1922
[Full Text]
Reid, G. J., Seidelin, P. H., Kop, W. J., Irvine, M. J., Strauss, B. H., Nolan, R. P., Lau, H. K., Yeo, E. L.
(2009). Mental Stress-Induced Platelet Activation Among Patients With Coronary Artery Disease. Psychosom. Med.
71: 438-445
[Abstract][Full Text]
Ries, T., Siemonsen, S., Grzyska, U., Zeumer, H., Fiehler, J.
(2009). Abciximab Is a Safe Rescue Therapy in Thromboembolic Events Complicating Cerebral Aneurysm Coil Embolization: Single Center Experience in 42 Cases and Review of the Literature. Stroke
40: 1750-1757
[Abstract][Full Text]
Smyth, S. S., Woulfe, D. S., Weitz, J. I., Gachet, C., Conley, P. B., Goodman, S. G., Roe, M. T., Kuliopulos, A., Moliterno, D. J., French, P. A., Steinhubl, S. R., Becker, R. C., for the 2008 Platelet Colloquium Participants,
(2009). G-Protein-Coupled Receptors as Signaling Targets for Antiplatelet Therapy. Arterioscler. Thromb. Vasc. Bio.
29: 449-457
[Abstract][Full Text]
Fung, A. Y., Saw, J., Starovoytov, A., Densem, C., Jokhi, P., Walsh, S. J., Fox, R. S., Humphries, K. H., Aymong, E., Ricci, D. R., Webb, J. G., Hamburger, J. N., Carere, R. G., Buller, C. E.
(2009). Abbreviated infusion of eptifibatide after successful coronary intervention The BRIEF-PCI (Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention) randomized trial.. J Am Coll Cardiol
53: 837-845
[Abstract][Full Text]
Mahmud, E., Prasad, A.
(2009). Optimal antiplatelet therapy during percutaneous coronary interventions includes glycoprotein IIb/IIIa inhibitors just eliminate the infusion.. J Am Coll Cardiol
53: 846-848
[Full Text]
Iijima, R., Ndrepepa, G., Mehilli, J., Byrne, R. A., Schulz, S., Neumann, F.-J., Richardt, G., Berger, P. B., Schomig, A., Kastrati, A.
(2009). Profile of bleeding and ischaemic complications with bivalirudin and unfractionated heparin after percutaneous coronary intervention. Eur Heart J
30: 290-296
[Abstract][Full Text]
Gumina, R. J., Yang, E. H., Sandhu, G. S., Prasad, A., Bresnahan, J. F., Lennon, R. J., Rihal, C. S., Holmes, D. R. Jr, Singh, M.
(2008). Survival Benefit With Concomitant Clopidogrel and Glycoprotein IIb/IIIa Inhibitor Therapy at Ad Hoc Percutaneous Coronary Intervention. Mayo Clin Proc.
83: 995-1001
[Abstract][Full Text]
Patel, S. S., Rana, H., Mascarenhas, D. A. N.
(2008). Intracoronary Abciximab Use in Patients Undergoing PCI at a Community Hospital: A Single Operator Experience. J CARDIOVASC PHARMACOL THER
13: 89-93
[Abstract]
Hirsh, J., Bauer, K. A., Donati, M. B., Gould, M., Samama, M. M., Weitz, J. I.
(2008). Parenteral Anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 141S-159S
[Abstract][Full Text]
Patrono, C., Baigent, C., Hirsh, J., Roth, G.
(2008). Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 199S-233S
[Abstract][Full Text]
Schulman, S., Beyth, R. J., Kearon, C., Levine, M. N.
(2008). Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 257S-298S
[Abstract][Full Text]
Harrington, R. A., Becker, R. C., Cannon, C. P., Gutterman, D., Lincoff, A. M., Popma, J. J., Steg, G., Guyatt, G. H., Goodman, S. G.
(2008). Antithrombotic Therapy for Non-ST-Segment Elevation Acute Coronary Syndromes: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 670S-707S
[Abstract][Full Text]
Feit, F., Manoukian, S. V., Ebrahimi, R., Pollack, C. V., Ohman, E. M., Attubato, M. J., Mehran, R., Stone, G. W.
(2008). Safety and Efficacy of Bivalirudin Monotherapy in Patients With Diabetes Mellitus and Acute Coronary Syndromes: A Report From the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial. J Am Coll Cardiol
51: 1645-1652
[Abstract][Full Text]
Kereiakes, D. J., Gurbel, P. A.
(2008). Peri-Procedural Platelet Function and Platelet Inhibition in Percutaneous Coronary Intervention. J Am Coll Cardiol Intv
1: 111-121
[Abstract][Full Text]
Ndrepepa, G., Berger, P. B., Mehilli, J., Seyfarth, M., Neumann, F.-J., Schomig, A., Kastrati, A.
(2008). Periprocedural Bleeding and 1-Year Outcome After Percutaneous Coronary Interventions Appropriateness of Including Bleeding as a Component of a Quadruple End Point.. J Am Coll Cardiol
51: 690-697
[Abstract][Full Text]
Ndrepepa, G., Kastrati, A., Mehilli, J., Neumann, F.-J., ten Berg, J., Bruskina, O., Dotzer, F., Seyfarth, M., Pache, J., Dirschinger, J., Berger, P. B., Schomig, A.
(2008). One-year clinical outcomes with abciximab vs. placebo in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention after pre-treatment with clopidogrel: results of the ISAR-REACT 2 randomized trial. Eur Heart J
29: 455-461
[Abstract][Full Text]
Hertzberg, V., Chimowitz, M., Lynn, M., Chester, C., Asbury, W., Cotsonis, G.
(2008). Use of dose modification schedules is effective for blinding trials of warfarin: evidence from the WASID study. Clin Trials
5: 23-30
[Abstract]
Granger, C. B, Vogel, V., Cummings, S. R, Held, P., Fiedorek, F., Lawrence, M., Neal, B., Reidies, H., Santarelli, L., Schroyer, R., Stockbridge, N. L, Feng Zhao,
(2008). Do we need to adjudicate major clinical events?. Clin Trials
5: 56-60
[Abstract]
Dabbous, O H, Anderson, F A Jr, Gore, J M, Eagle, K A, Fox, K A A, Mehta, R H, Goldberg, R J, Agnelli, G, Steg, P G, for the GRACE Investigators,
(2008). Outcomes with the use of glycoprotein IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes. Heart
94: 159-165
[Abstract][Full Text]
Jaumdally, R. J., Varma, C., Blann, A. D., MacFadyen, R. J., Lip, G. Y. H.
(2007). Platelet Activation in Coronary Artery Disease: Intracardiac vs Peripheral Venous Levels and the Effects of Angioplasty. Chest
132: 1532-1539
[Abstract][Full Text]
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B.
(2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol
50: e1-e157
[Full Text]
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B.
(2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol
50: 652-726
[Full Text]
Levy, E.I., Mehta, R., Gupta, R., Hanel, R.A., Chamczuk, A.J., Fiorella, D., Woo, H.H., Albuquerque, F.C., Jovin, T.G., Horowitz, M.B., Hopkins, L.N.
(2007). Self-Expanding Stents for Recanalization of Acute Cerebrovascular Occlusions. Am. J. Neuroradiol.
28: 816-822
[Abstract][Full Text]
Heyde, G. S., Koch, K. T., de Winter, R. J., Dijkgraaf, M. G.W., Klees, M. I., Dijksman, L. M., Piek, J. J., Tijssen, J. G.P.
(2007). Randomized Trial Comparing Same-Day Discharge With Overnight Hospital Stay After Percutaneous Coronary Intervention: Results of the Elective PCI in Outpatient Study (EPOS). Circulation
115: 2299-2306
[Abstract][Full Text]
Montalescot, G., Antoniucci, D., Kastrati, A., Neumann, F. J., Borentain, M., Migliorini, A., Boutron, C., Collet, J.-P., Vicaut, E.
(2007). Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-up. Eur Heart J
28: 443-449
[Abstract][Full Text]
Antoniucci, D.
(2007). Differences among GP IIb/IIIa inhibitors: different clinical benefits in non-ST-segment elevation acute coronary syndrome percutaneous coronary intervention patients. Eur Heart J Suppl
9: A32-A36
[Abstract][Full Text]
Raveendran, G., Ting, H. H., Best, P. J., Holmes, D. R. Jr, Lennon, R. J., Singh, M., Bell, M. R., Long, K. H., Rihal, C. S.
(2007). Eptifibatide vs Abciximab as Adjunctive Therapy During Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction. Mayo Clin Proc.
82: 196-202
[Abstract][Full Text]
Johnston, S. L
(2007). Biologic therapies: what and when?. J. Clin. Pathol.
60: 8-17
[Abstract][Full Text]
Dzau, V. J., Antman, E. M., Black, H. R., Hayes, D. L., Manson, J. E., Plutzky, J., Popma, J. J., Stevenson, W.
(2006). The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part I: Pathophysiology and Clinical Trial Evidence (Risk Factors Through Stable Coronary Artery Disease). Circulation
114: 2850-2870
[Full Text]
Mixon, T. A., Dehmer, G. J.
(2006). Drive-Through Angioplasty: Is It Safe or Necessary?. Circulation
114: 2578-2580
[Full Text]
Bertrand, O. F., De Larochelliere, R., Rodes-Cabau, J., Proulx, G., Gleeton, O., Manh Nguyen, C., Dery, J.-P., Barbeau, G., Noel, B., Larose, E., Poirier, P., Roy, L., for the Early Discharge After Transradial Stenting,
(2006). A Randomized Study Comparing Same-Day Home Discharge and Abciximab Bolus Only to Overnight Hospitalization and Abciximab Bolus and Infusion After Transradial Coronary Stent Implantation. Circulation
114: 2636-2643
[Abstract][Full Text]
Ndrepepa, G., Kastrati, A., Mehilli, J., Neumann, F.-J., ten Berg, J., Bruskina, O., Dotzer, F., Seyfarth, M., Pache, J., Dirschinger, J., Ulm, K., Berger, P. B., Schomig, A.
(2006). Age-Dependent Effect of Abciximab in Patients With Acute Coronary Syndromes Treated With Percutaneous Coronary Interventions. Circulation
114: 2040-2046
[Abstract][Full Text]
Saw, J., Bhatt, D. L., Moliterno, D. J., Brener, S. J., Steinhubl, S. R., Lincoff, A. M., Tcheng, J. E., Harrington, R. A., Simoons, M., Hu, T., Sheikh, M. A., Kereiakes, D. J., Topol, E. J.
(2006). The Influence of Peripheral Arterial Disease on Outcomes: A Pooled Analysis of Mortality in Eight Large Randomized Percutaneous Coronary Intervention Trials. J Am Coll Cardiol
48: 1567-1572
[Abstract][Full Text]
Deliargyris, E. N., Upadhya, B., Melton, L. G., Thompson, C., Fisher, M., Gabriel, D. A., Dehmer, G. J., Sane, D. C.
(2006). Unfractionated Heparin Reduces the Anti-Platelet Effects of Abciximab but not Eptifibatide During PCI. CLIN APPL THROMB HEMOST
12: 458-464
[Abstract]
Bertrand, M. E., Van Belle, E.
(2006). Triple antiplatelet treatment in patients presenting with non-ST-segment elevation acute coronary syndromes. Eur Heart J Suppl
8: G59-G63
[Abstract][Full Text]
Gibson, C. M., Morrow, D. A., Murphy, S. A., Palabrica, T. M., Jennings, L. K., Stone, P. H., Lui, H. H., Bulle, T., Lakkis, N., Kovach, R., Cohen, D. J., Fish, P., McCabe, C. H., Braunwald, E., for the TIMI Study Group,
(2006). A Randomized Trial to Evaluate the Relative Protection Against Post-Percutaneous Coronary Intervention Microvascular Dysfunction, Ischemia, and Inflammation Among Antiplatelet and Antithrombotic Agents: The PROTECT-TIMI-30 Trial. J Am Coll Cardiol
47: 2364-2373
[Abstract][Full Text]
Rasoul, S., Ottervanger, J. P., de Boer, M.-J., Miedema, K., Hoorntje, J. C.A., Gosselink, M., Zijlstra, F., Suryapranata, H., Dambrink, J.-H. E., van 't Hof, A. W.J.
(2006). A comparison of dual vs. triple antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndrome: results of the ELISA-2 trial. Eur Heart J
27: 1401-1407
[Abstract][Full Text]
Sharma, S., Makkar, R., Lardizabal, J.
(2006). Intracoronary Administration of Abciximab During Percutaneous Coronary Interventions: Should This Be the Routine and Preferred Approach?. J CARDIOVASC PHARMACOL THER
11: 136-141
[Abstract]
Okmen, E., Sanli, A., Uyarel, H., Dayi, S., Tartan, Z., Cam, N.
(2006). Impacts of Glycoprotein IIb/IIIa Inhibition on QT Dispersion After Successful Percutaneous Coronary Intervention. ANGIOLOGY
57: 273-281
[Abstract]
Miller, W. L., Garratt, K. N., Burritt, M. F., Lennon, R. J., Reeder, G. S., Jaffe, A. S.
(2006). Baseline troponin level: key to understanding the importance of post-PCI troponin elevations. Eur Heart J
27: 1061-1069
[Abstract][Full Text]
Stone, G. W., Aronow, H. D.
(2006). Long-term Care After Percutaneous Coronary Intervention: Focus on the Role of Antiplatelet Therapy. Mayo Clin Proc.
81: 641-652
[Abstract][Full Text]
Kim, W., Jeong, M. H., Kim, K. H., Sohn, I. S., Hong, Y. J., Park, H. W., Kim, J. H., Ahn, Y. K., Cho, J. G., Park, J. C., Cho, D. L., Kang, J. C.
(2006). The Clinical Results of a Platelet Glycoprotein IIb/IIIa Receptor Blocker (Abciximab: ReoPro)-Coated Stent in Acute Myocardial Infarction. J Am Coll Cardiol
47: 933-938
[Abstract][Full Text]
Okmen, E., Cam, N., Sanli, A., Unal, S., Tartan, Z., Vural, M.
(2006). Cardiac Troponin I Increase After Successful Percutaneous Coronary Angioplasty: Predictors and Long-Term Prognostic Value. ANGIOLOGY
57: 161-169
[Abstract]
Puma, J. A., Banko, L. T., Pieper, K. S., Sacchi, T. J., O'Shea, J. C., Dery, J. P., Tcheng, J. E.
(2006). Clinical Characteristics Predict Benefits From Eptifibatide Therapy During Coronary Stenting: Insights From the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) Trial. J Am Coll Cardiol
47: 715-718
[Abstract][Full Text]
Colombo, A., Stankovic, G.
(2006). The Value of Selectivity. J Am Coll Cardiol
47: 719-720
[Full Text]
Rao, S. V., O'Grady, K., Pieper, K. S., Granger, C. B., Newby, L. K., Mahaffey, K. W., Moliterno, D. J., Lincoff, A. M., Armstrong, P. W., Van de Werf, F., Califf, R. M., Harrington, R. A.
(2006). A Comparison of the Clinical Impact of Bleeding Measured by Two Different Classifications Among Patients With Acute Coronary Syndromes. J Am Coll Cardiol
47: 809-816
[Abstract][Full Text]
Glaser, R., Glick, H. A., Herrmann, H. C., Kimmel, S. E.
(2006). The Role of Risk Stratification in the Decision to Provide Upstream Versus Selective Glycoprotein IIb/IIIa Inhibitors for Acute Coronary Syndromes: A Cost-Effectiveness Analysis. J Am Coll Cardiol
47: 529-537
[Abstract][Full Text]
Staelens, S., Hadders, M. A., Vauterin, S., Platteau, C., De Maeyer, M., Vanhoorelbeke, K., Huizinga, E. G., Deckmyn, H.
(2006). Paratope Determination of the Antithrombotic Antibody 82D6A3 Based on the Crystal Structure of Its Complex with the von Willebrand Factor A3-Domain. J. Biol. Chem.
281: 2225-2231
[Abstract][Full Text]
Bittl, J. A.
(2005). Reducing the Risk of Emergency Bypass Surgery for Failed Percutaneous Coronary Interventions. J Am Coll Cardiol
46: 2010-2012
[Full Text]
Mukherjee, D., Topol, E. J., Bertrand, M. E., Kristensen, S. D., Herrmann, H. C., Neumann, F.-J., Yakubov, S. J., Bassand, J.-P., McClure, R. R., Stone, G. W., Ardissino, D., Moliterno, D. J., for the TARGET Investigators,
(2005). Mortality at 1 year for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularization: do tirofiban and ReoPro give similar efficacy outcomes at trial 1-year follow-up. Eur Heart J
26: 2524-2528
[Abstract][Full Text]
Dorffler-Melly, J., Mahler, F., Do, D.-D., Triller, J., Baumgartner, I.
(2005). Adjunctive Abciximab Improves Patency and Functional Outcome in Endovascular Treatment of Femoropopliteal Occlusions: Initial Experience. Radiology
237: 1103-1109
[Abstract][Full Text]
Dawkins, K D, Gershlick, T, de Belder, M, Chauhan, A, Venn, G, Schofield, P, Smith, D, Watkins, J, Gray, H H, Joint Working Group on Percutaneous Coronary Inter,
(2005). Percutaneous coronary intervention: recommendations for good practice and training. Heart
91: vi1-vi27
[Abstract][Full Text]
Freedman, J. E.
(2005). Molecular Regulation of Platelet-Dependent Thrombosis. Circulation
112: 2725-2734
[Abstract][Full Text]
Coons, J. C, Seybert, A. L, Saul, M. I, Kirisci, L., Kane-Gill, S. L
(2005). Outcomes and Costs of Abciximab Versus Eptifibatide for Percutaneous Coronary Intervention. The Annals of Pharmacotherapy
39: 1621-1626
[Abstract][Full Text]
King, S. B. III, Dangas, G., Moses, J. W., King, S. B. III, Dangas, G., Moses, J. W.
(2005). Surgery Is Preferred for the Diabetic With Multivessel Disease. Circulation
112: 1500-1515
[Full Text]
Aviv, R. I., O'Neill, R., Patel, M. C., Colquhoun, I. R.
(2005). Abciximab in Patients with Ruptured Intracranial Aneurysms. Am. J. Neuroradiol.
26: 1744-1750
[Abstract][Full Text]
Nallamothu, B. K., Bates, E. R., Hochman, J. S., Granger, C. B., Guetta, V., Wilcox, R. G., White, H. D., Armstrong, P. W., Savonitto, S., Jia, G., Lincoff, A. M., Topol, E. J., for the GUSTO-V Investigators,
(2005). Prognostic implication of activated partial thromboplastin time after reteplase or half-dose reteplase plus abciximab: results from the GUSTO-V trial. Eur Heart J
26: 1506-1512
[Abstract][Full Text]
McKeown, P., Epstein, A. E.
(2005). Future Directions: American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery. Chest
128: 61S-64S
[Abstract][Full Text]
Ioannidis, J. P. A.
(2005). Contradicted and Initially Stronger Effects in Highly Cited Clinical Research. JAMA
294: 218-228
[Abstract][Full Text]
Kim, D. J., Lee, B. H., Kim, D. I., Shim, W. H., Jeon, P., Lee, T. H.
(2005). Stent-Assisted Angioplasty of Symptomatic Intracranial Vertebrobasilar Artery Stenosis: Feasibility and Follow-up Results. Am. J. Neuroradiol.
26: 1381-1388
[Abstract][Full Text]
Williams, D. O.
(2005). Clopidogrel Pretreatment for Percutaneous Coronary Intervention: Double, Double, Dose in Trouble?. Circulation
111: 2019-2021
[Full Text]
Authors/Task Force Members, , Silber, S., Albertsson, P., Aviles, F. F., Camici, P. G., Colombo, A., Hamm, C., Jorgensen, E., Marco, J., Nordrehaug, J.-E., Ruzyllo, W., Urban, P., Stone, G. W., Wijns, W.
(2005). Guidelines for Percutaneous Coronary Interventions: The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J
26: 804-847
[Full Text]
Villeneuve, E., Sunderji, R.
(2005). Glycoprotein IIb/IIIa Inhibitors in Patients with End-Stage Renal Disease. The Annals of Pharmacotherapy
39: 732-735
[Abstract][Full Text]
Large, G A
(2005). Contemporary management of acute coronary syndrome. Postgrad. Med. J.
81: 217-222
[Abstract][Full Text]
Claeys, M. J., Van der Planken, M. G., Bosmans, J. M., Michiels, J. J., Vertessen, F., Van Der Goten, P., Wuyts, F. L., Vrints, C. J.
(2005). Does pre-treatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein IIb/IIIa antagonists during elective coronary stenting? A focus on peri-procedural myonecrosis. Eur Heart J
26: 567-575
[Abstract][Full Text]
Brophy, J. M., Joseph, L.
(2005). Medical Decision Making with Incomplete Evidence--Choosing a Platelet Glycoprotein IIbIIIa Receptor Inhibitor for Percutaneous Coronary Interventions. Med Decis Making
25: 222-228
[Abstract]
Lansky, A. J., Hochman, J. S., Ward, P. A., Mintz, G. S., Fabunmi, R., Berger, P. B., New, G., Grines, C. L., Pietras, C. G., Kern, M. J., Ferrell, M., Leon, M. B., Mehran, R., White, C., Mieres, J. H., Moses, J. W., Stone, G. W., Jacobs, A. K., Endorsed by the American College of Cardiology Fou,
(2005). Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women: A Statement for Healthcare Professionals From the American Heart Association. Circulation
111: 940-953
[Abstract][Full Text]
Batyraliev, T., Ayalp, M. R., Sercelik, A., Karben, Z., Dinler, G., Besnili, F., Ozgul, S., Perchucov, I.
(2005). Complications of Cardiac Catheterization: A Single-Center Study. ANGIOLOGY
56: 75-80
[Abstract]
Pineo, G. F., Hull, R. D.
(2005). Low-Molecular-Weight Heparin for the Treatment of Venous Thromboembolism in the Elderly. CLIN APPL THROMB HEMOST
11: 15-23
[Abstract]
Armstrong, P. W., Newby, L. K., Granger, C. B., Lee, K. L., Simes, R. J., Van de Werf, F., White, H. D., Califf, R. M., for the Virtual Coordinating Centre for Global Col,
(2004). Lessons Learned From a Clinical Trial. Circulation
110: 3610-3614
[Full Text]
Ali, A., Hashem, M., Rosman, H. S., Moser, L., Rehan, A., Davis, T., Romanelli, M., LaLonde, T., Yamasaki, H., Barbish, B., Michael, J., Ali, S. A., Schreiber, T. L., Gardin, J. M.
(2004). Glycoprotein IIb/IIIa Receptor Antagonists and Risk of Bleeding: A Single-Center Experience in 1020 Patients. J Clin Pharmacol
44: 1328-1332
[Abstract][Full Text]
Brouse, S. D, Wiesehan, V. G
(2004). Evaluation of Bleeding Complications Associated with Glycoprotein IIb/IIIa Inhibitors. The Annals of Pharmacotherapy
38: 1783-1788
[Abstract][Full Text]
Wennberg, D. E., Lucas, F. L., Siewers, A. E., Kellett, M. A., Malenka, D. J.
(2004). Outcomes of Percutaneous Coronary Interventions Performed at Centers Without and With Onsite Coronary Artery Bypass Graft Surgery. JAMA
292: 1961-1968
[Abstract][Full Text]
Wiggins, B. S., Spinler, S.
(2004). Antiplatelet and Antithrombin Therapy for Early Management of Acute Coronary Syndromes. Journal of Pharmacy Practice
17: 347-369
[Abstract]
Ernst, N. M.S.K.J., Suryapranata, H., Miedema, K., Slingerland, R. J., Ottervanger, J. P., Hoorntje, J. C.A., Gosselink, A.T.M., Dambrink, J.-H. E., de Boer, M.-J., Zijlstra, F., van't Hof, A. W.J.
(2004). Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Am Coll Cardiol
44: 1187-1193
[Abstract][Full Text]
Ndrepepa, G., Kastrati, A., Neumann, F.-J., Schmitt, C., Mehilli, J., Schomig, A.
(2004). Five-year outcome of patients with acute myocardial infarction enrolled in a randomised trial assessing the value of abciximab during coronary artery stenting. Eur Heart J
25: 1635-1640
[Abstract][Full Text]
McCaul, K A, Hobbs, M S T, Knuiman, M W, Rankin, J M, Gilfillan, I
(2004). Trends in two year risk of repeat revascularisation or death from cardiovascular disease after coronary artery bypass grafting or percutaneous coronary intervention in Western Australia, 1980-2001. Heart
90: 1042-1046
[Abstract][Full Text]
Hirsh, J., Raschke, R.
(2004). Heparin and Low-Molecular-Weight Heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 188S-203S
[Abstract][Full Text]
Patrono, C., Coller, B., FitzGerald, G. A., Hirsh, J., Roth, G.
(2004). Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 234S-264S
[Abstract][Full Text]
Levine, M. N., Raskob, G., Beyth, R. J., Kearon, C., Schulman, S.
(2004). Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 287S-310S
[Abstract][Full Text]
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