Original Article
Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention
N Engl J Med 2008; 359:688-696August 14, 2008
- Abstract
Background
Whether bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel is unknown.
Methods
We enrolled 4570 patients with stable or unstable angina (with normal levels of troponin T and creatine kinase MB) who were undergoing PCI after pretreatment with a 600-mg dose of clopidogrel at least 2 hours before the procedure; 2289 patients were randomly assigned in a double-blind manner to receive bivalirudin, and 2281 to receive unfractionated heparin. The primary end point was the composite of death, myocardial infarction, urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization (with a net clinical benefit defined as a reduction in the incidence of the end point). The secondary end point was the composite of death, myocardial infarction, or urgent target-vessel revascularization.
Results
The incidence of the primary end point was 8.3% (190 patients) in the bivalirudin group as compared with 8.7% (199 patients) in the unfractionated-heparin group (relative risk, 0.94; 95% confidence interval [CI], 0.77 to 1.15; P=0.57). The secondary end point occurred in 134 patients (5.9%) in the bivalirudin group and 115 patients (5.0%) in the unfractionated-heparin group (relative risk, 1.16; 95% CI, 0.91 to 1.49; P=0.23). The incidence of major bleeding was 3.1% (70 patients) in the bivalirudin group and 4.6% (104 patients) in the unfractionated-heparin group (relative risk, 0.66; 95% CI, 0.49 to 0.90; P=0.008).
Conclusions
In patients with stable and unstable angina who underwent PCI after pretreatment with clopidogrel, bivalirudin did not provide a net clinical benefit (i.e., it did not reduce the incidence of the composite end point of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding) as compared with unfractionated heparin, but it did significantly reduce the incidence of major bleeding. (ClinicalTrials.gov number, NCT00262054.)
Media in This Article
Figure 1. 30
30-Day Cumulative Incidence of the Primary End Point and the Secondary End Point in the Bivalirudin Group and the Unfractionated-Heparin Group.Figure 2. 30
30-Day Incidence and Relative Risk of the Primary End Point of Death, Myocardial Infarction, Urgent Target-Vessel Revascularization, or Major Bleeding in Prespecified Subgroups.Article Activity
- Article
Percutaneous coronary intervention (PCI) is commonly used to treat patients with coronary artery disease. To minimize the risk of thrombotic complications during and shortly after the procedure, many different antithrombotic regimens have been investigated and are currently in use. Increasing evidence of the adverse consequences of periprocedural bleeding suggests that protection from thrombotic complications should not be the sole measure by which antithrombotic therapies are evaluated.1 Aspirin, clopidogrel, and heparin are established antithrombotic drugs that are widely recommended according to current guidelines on PCI.2
Pretreatment with 300 to 600 mg of clopidogrel increasingly is used before PCI because of mounting evidence that it improves outcomes.3-8 Bivalirudin is a relatively new direct thrombin inhibitor that has been extensively investigated as a periprocedural antithrombotic therapy.8-13 In most of these studies, bivalirudin has been compared with heparin plus a glycoprotein IIb/IIIa antagonist8,11,13; in only one study was bivalirudin compared with unfractionated heparin in patients undergoing PCI.9 Although bivalirudin did reduce the incidence of bleeding complications as compared with heparin in that trial, the exclusive use of balloon angioplasty, the lack of pretreatment (or any treatment) with clopidogrel, the high dose of heparin administered (a bolus of 175 U per kilogram of body weight, followed by an 18-to-24-hour infusion), and the outdated regimen of bivalirudin make the trial results largely irrelevant to current interventional practice.9 The aim of the current study was to compare bivalirudin with unfractionated heparin in patients who had stable or unstable angina pectoris and who were undergoing PCI with placement of a stent after pretreatment with 600 mg of clopidogrel.
Methods
Study Population
We enrolled patients in the study from September 2005 through January 2008 if they were older than 18 years of age; were undergoing PCI; had been pretreated with a 600-mg loading dose of clopidogrel at least 2 hours before the intervention; and had provided written informed consent. The exclusion criteria are listed in the Supplementary Appendix (available with the full text of this article at www.nejm.org). The study protocol was approved by the ethics committees of all participating centers. The authors designed the trial protocol, performed the data analysis, wrote the manuscript, and decided to submit it for publication. Data collection and monitoring of the trial were performed by the Intracoronary Stenting and Antithrombosis Research (ISAR) Center, which is affiliated with Deutsches Herzzentrum, in Munich, Germany. Nycomed Pharma, which at the time of this study distributed bivalirudin in Europe and which sponsored the study in part, had no role in the design of the study, collection and analysis of the data, writing of the manuscript, or the decision to submit the manuscript for publication. The principal investigator and the study chair vouch for the accuracy and completeness of the reported data.
Study Protocol
All patients who were enrolled in the trial received 600 mg of clopidogrel at least 2 hours before the PCI procedure. They also received 325 to 500 mg of aspirin. After the decision had been made to perform a coronary intervention, patients at each participating center underwent randomization in a double-blind manner with the use of opaque, sealed envelopes that contained the assignment. Before the guide wire had crossed the lesion, patients in the bivalirudin group received a bolus of 0.75 mg of bivalirudin per kilogram, followed by an infusion of 1.75 mg per kilogram per hour for the duration of the procedure. Patients in the heparin group received a bolus of 140 U of heparin per kilogram, followed by a placebo infusion for the duration of the procedure. Double-blinding was achieved by using identical vials for the study drugs in the two groups. At one center, where 42 patients were enrolled, an initial dose of 100 U of heparin per kilogram was given and a monitor of activated clotting time who was unaware of the treatment assignments administered additional boluses of heparin or placebo if the activated clotting time was less than 250 seconds. All caregivers were unaware of the values for activated clotting time.
Coronary stenting with either bare-metal or drug-eluting stents, according to the choice of the physician, was the preferred method of PCI. Vascular-access closure devices were used in 10% of the patients. Sheaths were removed and manual compression was applied as soon as the activated partial-thromboplastin time fell below 50 seconds. Postprocedural therapy included aspirin (80 to 325 mg per day indefinitely), clopidogrel (75 to 150 mg per day until discharge but for no longer than 3 days, followed by 75 mg per day for at least 1 month, in patients with bare-metal stents, or 6 months, in patients with drug-eluting stents), as well as all other cardiac medications that were recommended by the patients' physicians. The protocol provided for the performance of electrocardiography and the collection of blood samples for measurements of cardiac enzyme levels, hemoglobin levels, and platelet counts every 8 hours for the first 24 hours after the procedure and then daily until discharge (at least two samples were required after the procedure according to the protocol). Patients were interviewed by telephone at 30 days, and all patients with any cardiac symptoms underwent a complete clinical, electrocardiographic, and laboratory evaluation. The local research coordinators collected the data and forwarded them to the data coordinating center. Data quality was ensured by checking source documentation.
Study End Points and Definitions
The primary end point of the study was the combined incidence of death from any cause, myocardial infarction, urgent target-vessel revascularization (coronary bypass surgery or PCI) due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization. The quadruple end point was aimed at measuring the risk of both ischemic and bleeding complications and was the basis for determining the net clinical benefit of bivalirudin as compared with unfractionated heparin. Myocardial infarction was defined as the development of pathologic Q waves (≥30 msec in duration and ≥0.1 mV in depth) in two or more contiguous precordial leads or two or more adjacent limb leads, or an elevation of creatine kinase MB isoenzyme levels (or total creatine kinase if measures of creatine kinase MB were not available) to at least two times the upper limit of the normal range. The definition of major bleeding was the same as that used in the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial11: intracranial, intraocular, or retroperitoneal hemorrhage; clinically overt blood loss resulting in a decrease in hemoglobin of more than 3 g per deciliter; any decrease in hemoglobin of more than 4 g per deciliter; or transfusion of 2 or more units of packed red cells or whole blood.
The secondary end point of the study was the combined incidence of death from any cause, myocardial infarction, or urgent target-vessel revascularization. This triple end point was aimed at assessing the risk of ischemic complications.
We also evaluated the frequency of minor bleeding, which was defined as clinically overt bleeding that did not meet criteria for major bleeding,11 and of major and minor bleeding according to the Thrombolysis in Myocardial Infarction criteria.14 In addition, we evaluated the frequency of postprocedural myocardial infarction, defined as an elevation in creatine kinase MB to at least three times the upper limit of the normal range. Stent thrombosis was considered to have occurred when the Academic Research Consortium criteria for definite stent thrombosis were met.15 All events were adjudicated and classified by an event-adjudication committee whose members were unaware of the treatment assignments.
Statistical Analysis
We assumed that the primary end point would occur in 8% of patients in the unfractionated-heparin group (based on the incidence of the same composite outcome in the unfractionated-heparin group of a previous trial3 involving patients with normal levels of troponin T) and 5.8% in the bivalirudin group, which corresponds to a 27.5% risk reduction with bivalirudin. The planned enrollment of 4500 patients provided 82% power to detect this reduction at a two-sided alpha-error level of 0.05.
All analyses were performed in a blinded manner and were based on the intention-to-treat principle. Unblinding of the study groups was first done after completion of the statistical analyses. The data are presented as means ±SD or as counts or percentages. Categorical data were compared with the use of a chi-square test and Fisher's exact test when expected cell values were less than 5. Continuous data were compared with the use of Student's t-test, and the Kaplan–Meier method was used to assess event-free survival; comparisons were made with the use of the log-rank test. Prespecified subgroups for assessment of potential treatment differences were defined by age, sex, the presence or absence of diabetes, the baseline serum creatinine value, and stable or unstable angina. No formal adjustment for multiple testing was performed, and heterogeneity of treatment differences across the levels of a baseline variable was checked by assessing the interaction between assigned treatment and baseline variable with respect to the end point of interest.16 A two-sided P value of less than 0.05 was considered to indicate statistical significance. S-PLUS software, version 4.5 (Insightful), was used for all statistical analyses.
Results
One patient withdrew his consent after randomization but before receiving the assigned drug and was excluded from the analysis. In total, 4570 patients were included in the trial: 2289 patients assigned to the bivalirudin group and 2281 patients assigned to the unfractionated-heparin group. All these patients received the randomly assigned drug. Characteristics of the patients are shown in Table 1Table 1
Baseline Characteristics of the Patients., and characteristics of the lesions are shown in Table 2Table 2
Characteristics of the Lesions and Types of Intervention.. The average number of lesions treated per patient was 1.7±0.9 in both the bivalirudin and unfractionated-heparin groups (P=0.62). Glycoprotein IIb/IIIa antagonists were administered to four patients (0.2%) in each group. Only 19 patients (0.4%) did not complete the 30-day follow-up, and their data were censored at the last available contact (2 to 11 days after enrollment in the study).Table 3Table 3
Primary Quadruple End Point, Secondary Triple End Point, and Their Components. shows the incidence of ischemic and bleeding events in each study group. The primary end point of the study — the composite of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding — was reached by 190 patients in the bivalirudin group (8.3%) and 199 patients in the unfractionated-heparin group (8.7%) (relative risk, 0.94; 95% confidence interval [CI], 0.77 to 1.15; P=0.57) (Figure 1AFigure 1. 3030-Day Cumulative Incidence of the Primary End Point and the Secondary End Point in the Bivalirudin Group and the Unfractionated-Heparin Group.). The secondary, ischemic end point of the study — the composite of death, myocardial infarction, or urgent target-vessel revascularization — occurred in 134 patients in the bivalirudin group (5.9%) and 115 patients in the unfractionated-heparin group (5.0%) (relative risk, 1.16; 95% CI, 0.91 to 1.49; P=0.23) (Figure 1B).Definite stent thrombosis occurred in 12 patients in the bivalirudin group (0.5%) and 9 in the unfractionated-heparin group (0.4%, P=0.52). When an enzymatic threshold of three times the upper limit of the normal range was used for the diagnosis of postprocedural myocardial infarction, the combined incidence of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding was 6.9% in the bivalirudin group (157 patients) and 7.5% in the unfractionated-heparin group (171 patients, P=0.39). When we used that threshold for procedural infarction, the combined incidence of death, myocardial infarction, or urgent target-vessel revascularization was 4.4% in the bivalirudin group (100 patients) and 3.7% in the unfractionated-heparin group (84 patients, P=0.24). The primary end point did not differ significantly according to the study treatment in any of the prespecified subgroups (Figure 2Figure 2. 30
30-Day Incidence and Relative Risk of the Primary End Point of Death, Myocardial Infarction, Urgent Target-Vessel Revascularization, or Major Bleeding in Prespecified Subgroups.).Discussion
In this double-blind study, we compared bivalirudin and unfractionated heparin in patients who did not have elevated levels of biomarkers, who had stable or unstable angina, and who were undergoing PCI after having received pretreatment with 600 mg of clopidogrel at least 2 hours before the procedure. The main finding was that bivalirudin did not significantly reduce the incidence of the quadruple end point — that is, did not provide a net clinical benefit — as compared with unfractionated heparin at 30 days, although it did significantly reduce the incidence of bleeding.
The results of this study should be interpreted in the context of the specific settings in which it was performed. Patients enrolled in this trial did not have elevated levels of biomarkers (troponin T and creatine kinase MB) at study entry and had been pretreated with 600 mg of clopidogrel for at least 2 hours before PCI, which was performed predominantly on an elective basis. In addition, the trial was sufficiently powered to prove a 27.5% risk reduction with bivalirudin. Assumptions based on a smaller risk reduction would require clinical trials with a larger number of patients.
We chose the quadruple end point — the composite of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding — as the primary end point of the present trial for two main reasons. First, it will permit clinicians to put the present trial in context with other studies of bivalirudin that have used the same end point.8,11-13 Second, recent findings suggest that both myocardial infarction and bleeding that occur after the procedure have similar prognostic value in terms of 1-year mortality.1 We acknowledge that our sample is much too small for an assessment of mortality as the sole end point. We also acknowledge that when two drugs compared in a study show different effects on the risk of myocardial infarction (a trend favoring unfractionated heparin) and bleeding (a significant reduction with bivalirudin), as in the present trial, interpretation of the overall trial result might become more difficult. However, we believe that inclusion of bleeding in the primary outcome better informs clinicians about the morbidity they can expect when choosing antithrombotic therapy during PCI.
We are not aware of any studies that have been performed to identify the most appropriate dose of bivalirudin or unfractionated heparin (in patients not receiving a glycoprotein IIb/IIIa inhibitor). After initial studies involving higher doses of bivalirudin with prolonged postprocedural infusions,9 the dose was reduced,17 and the current preferred regimen, as used in the present trial, consists of a bolus of 0.75 mg per kilogram followed by an infusion of 1.75 mg per kilogram per hour for the duration of the procedure, without monitoring of the activated clotting time.8 Two regimens of unfractionated heparin are currently in use: one in which the dose is based on the activated clotting time (used in the majority of centers in the United States) and one in which a weight-adjusted dose is administered without monitoring of the activated clotting time (used in the majority of European centers). An analysis of pooled data from six randomized trials in which the activated clotting time was monitored revealed that the mean total dose of heparin administered was 14,203 U; 60% of this dose was given as an initial bolus, and the remainder was administered on the basis of the activated clotting time.18 This is higher than the total dose of heparin administered in the present trial. In that same analysis, a higher dose of heparin was associated with fewer ischemic complications but more bleeding. That analysis suggested an optimal range for the activated clotting time of 300 to 375 seconds.18 However, a more recent trial has shown that the target activated clotting time of 300 to 350 seconds, which is recommended by current guidelines in the United States, was achieved in less than 20% of the patients.19 Thus, the optimal regimen of heparin during PCI remains unknown. It is plausible that a lower dose of heparin than that used in our study would have led to a lower rate of bleeding, diminishing the advantage seen with the use of bivalirudin in terms of a lower risk of bleeding.
The value of pretreatment with 300 mg of clopidogrel before PCI has been evaluated in several trials in the past decade.7,20,21 More recently, trials have shown that a larger loading dose (600 mg) achieves more rapid and more potent inhibition of platelet aggregation than does a dose of 300 mg.22-24 The antiplatelet effect of a 600-mg dose of clopidogrel, administered to all the patients in our trial, might have contributed to our findings, in view of previous studies indicating that heparin actually activates platelets; bivalirudin does not.25
New findings from various clinical trials of antithrombotic drugs highlight the relevance of bleeding as a predictor of 1-year mortality.1,26 Yet, despite the association between bleeding and mortality, no difference in 1-year mortality with bivalirudin was seen in the largest trial of its use.27 Although in our study, insufficient power to detect a difference in mortality, if one did exist, undoubtedly contributed to the lack of an observed difference in mortality, the trend toward a higher incidence of postprocedural myocardial infarction in the bivalirudin group than in the unfractionated-heparin group might also have blunted any benefit one might have anticipated with bivalirudin, in view of the lower rate of bleeding with bivalirudin.
In conclusion, in patients who did not have elevated levels of biomarkers, who had stable or unstable angina, and who were undergoing PCI (with placement of a drug-eluting stent in most of the patients) after pretreatment with 600 mg of clopidogrel, bivalirudin did not provide a net clinical benefit. That is, as compared with unfractionated heparin, it did not reduce the incidence of the quadruple end point at 30 days, although it significantly reduced the incidence of bleeding.
Supported in part by Nycomed Pharma, Unterschleißheim, Germany, and by a grant from Deutsches Herzzentrum, Munich, Germany (KKF 1.1-05, 984323).
Dr. Kastrati reports receiving lecture fees from Bristol-Myers Squibb, Cordis, Lilly, Medtronic, and Sanofi-Aventis; Dr. Byrne, being a research fellow of the Irish Board for Training in Cardiovascular Medicine, sponsored by A. Menarini Pharmaceuticals; Dr. Khattab, serving as a consultant to Boston Scientific and receiving lecture fees from Boston Scientific, Cordis, and Medtronic; Dr. Blankenship, receiving lecture fees from Sanofi-Aventis; Dr. Seyfarth, serving as a consultant to Abiomed and Sanofi-Aventis and receiving lecture fees from Lilly and Novartis; Dr. Richardt, receiving lecture fees from Boston Scientific and Cordis and grant support from Bristol-Myers Squibb; and Dr. Berger, serving as a consultant to Daiichi Sankyo–Lilly and PlaCor. No other potential conflict of interest relevant to this article was reported.
Source Information
From Deutsches Herzzentrum, Technische Universität, Munich (A.K., J. Mehilli, R.A.B., R.I., S.S., J.P., M.S., I.G., A.S.); Herz-Zentrum, Bad Krozingen (F.-J.N., H.J.B., J. Minners); Herzzentrum der Segeberger Kliniken, Bad Segeberg (A.A.K., G.R.); and 1.Medizinische Klinik rechts der Isar, Technische Universität, Munich (J.D., A.S.) — all in Germany; and Geisinger Medical Center, Danville, PA (J.C.B., K.A.S., P.B.B.).
Address reprint requests to Dr. Kastrati at Deutsches Herzzentrum, Lazarettstr. 36, 80636 Munich, Germany, or at kastrati@dhm.mhn.de.
The investigators who participated in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 3) trial are listed in the Appendix.
Appendix
The following centers and investigators participated in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 3) Trial: Steering committee — A. Schömig (chair), A. Kastrati (principal investigator), F.-J. Neumann; Data Coordinating Center — J. Mehilli (director), S. Schulz, H. Holle, F. Maimer-Rodrigues, K. Hösl, C. Peterle, E. Türk, M. Dirlewanger, N. Sargon, S. Kufner, C. Roth; Data and Safety Monitoring Board — J. Mann (chair), F. Hoffmann, M. Schwaiger, K. Ulm (biostatistician); Angiographic Core Laboratory — R. Iijima, R. Byrne, O. Bruskina, S. Piniek, S. Hurt; Study Sites and Investigators — Germany: Deutsches Herzzentrum, Munich: J. Pache (principal investigator), M. Seyfarth, D. Zohlnhöfer, M. Karch, J. Hausleiter, S. Massberg, I. Graf, L. Pavlovic; Herz-Zentrum, Bad Krozingen: F.-J. Neumann (principal investigator), H.-J. Büttner, J. Minners, H.P. Bestehorn, K.D. Werner, M. Gick, T. Comberg, M. Ferenc, J. Rothe, J. Allgeier, K. Peitz, S. Waldmann, J. Korb; 1.Medizinische Klinik rechts der Isar, Munich: J. Dirschinger (principal investigator), N. von Beckerath, I. Ott, K.L. Laugwitz, S. Meyer; Herzzentrum der Segeberger Kliniken, Bad Segeberg: G. Richardt (principal investigator), A. Khattab, V. Geist, M. Abdel-Wahab; Klinikum Garmisch-Partenkirchen: F. Dotzer (principal investigator), C. Glatthor, M. Fleckenstein, M. Adelt, M. Deters; Herz-und Gefäß-Klinik, Bad Neustadt: M. Schneider (principal investigator), S. Kerber, B. Schumacher, G. Rosshirt; United States: Geisinger Clinic, Danville, PA: P.B. Berger (principal investigator), J. Blankenship, K.A. Skelding, T. Scott, D. Zimmerman, A. Temple, L. Belles.
- References
References
1
Ndrepepa G ,Berger PB ,Mehilli J , et al. 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 2008;51:690-697
CrossRef | Web of Science | Medline2
Smith SC Jr ,Feldman TE ,Hirshfeld JW Jr , et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006;47:e1-e121
CrossRef | Medline3
Kastrati A ,Mehilli J ,Schuhlen H , et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004;350:232-238
Full Text | Web of Science | Medline4
Mehilli J ,Kastrati A ,Schuhlen H , et al. Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel. Circulation 2004;110:3627-3635
CrossRef | Web of Science | Medline5
Kastrati A ,Mehilli J ,Neumann FJ , et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006;295:1531-1538
CrossRef | Web of Science | Medline6
Stone GW ,White HD ,Ohman EM , et al. Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet 2007;369:907-919
CrossRef | Web of Science | Medline7
Sabatine MS ,Cannon CP ,Gibson CM , et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005;294:1224-1232
CrossRef | Web of Science | Medline8
Stone GW ,Witzenbichler B ,Guagliumi G , et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358:2218-2230
Full Text | Web of Science | Medline9
Bittl JA ,Strony J ,Brinker JA , et al. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med 1995;333:764-769
Full Text | Web of Science | Medline10
Lincoff AM ,Kleiman NS ,Kottke-Marchant K , et al. Bivalirudin with planned or provisional abciximab versus low-dose heparin and abciximab during percutaneous coronary revascularization: results of the Comparison of Abciximab Complications with Hirulog for Ischemic Events Trial (CACHET). Am Heart J 2002;143:847-853
CrossRef | Web of Science | Medline11
Lincoff AM ,Bittl JA ,Harrington RA , et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003;289:853-863[Erratum, JAMA 2003;289:1638.]
CrossRef | Web of Science | Medline12
Lincoff AM ,Bittl JA ,Kleiman NS , et al. Comparison of bivalirudin versus heparin during percutaneous coronary intervention (the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events [REPLACE]-1 trial). Am J Cardiol 2004;93:1092-1096
CrossRef | Web of Science | Medline13
Stone GW ,McLaurin BT ,Cox DA , et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203-2216
Full Text | Web of Science | Medline14
The TIMI Study Group. Definitions used in TIMI trials. (Accessed July 21, 2008, at http://www.timi.org/.)
15
Mauri L ,Hsieh W ,Massaro JM ,Ho KKL ,D'Agostino R ,Cutlip DE . Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007;356:1020-1029
Full Text | Web of Science | Medline16
Wang R ,Lagakos SW ,Ware JH ,Hunter DJ ,Drazen JM . Statistics in medicine -- reporting of subgroup analyses in clinical trials. N Engl J Med 2007;357:2189-2194
Full Text | Web of Science | Medline17
Kong DF ,Topol EJ ,Bittl JA , et al. Clinical outcomes of bivalirudin for ischemic heart disease. Circulation 1999;100:2049-2053
Web of Science | Medline18
Chew DP ,Bhatt DL ,Lincoff AM , et al. Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials. Circulation 2001;103:961-966
Web of Science | Medline19
Montalescot G ,White HD ,Gallo R , et al. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006;355:1006-1017
Full Text | Web of Science | Medline20
Mehta SR ,Yusuf S ,Peters RJ , et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527-533
CrossRef | Web of Science | Medline21
Steinhubl SR ,Berger PB ,Mann JT III , et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-2420[Erratum, JAMA 2003;289:987.]
CrossRef | Web of Science | Medline22
Montalescot G ,Sideris G ,Meuleman C , et al. A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol 2006;48:931-938
CrossRef | Web of Science | Medline23
Price MJ ,Coleman JL ,Steinhubl SR ,Wong GB ,Cannon CP ,Teirstein PS . Onset and offset of platelet inhibition after high-dose clopidogrel loading and standard daily therapy measured by a point-of-care assay in healthy volunteers. Am J Cardiol 2006;98:681-684
CrossRef | Web of Science | Medline24
von Beckerath N ,Taubert D ,Pogatsa-Murray G ,Schomig E ,Kastrati A ,Schomig A . Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation 2005;112:2946-2950
Web of Science | Medline25
Eikelboom J ,White H ,Yusuf S . The evolving role of direct thrombin inhibitors in acute coronary syndromes. J Am Coll Cardiol 2003;41:Suppl S:70S-78S
CrossRef | Web of Science | Medline26
Feit F ,Voeltz MD ,Attubato MJ , et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 Trial. Am J Cardiol 2007;100:1364-1369
CrossRef | Web of Science | Medline27
Stone GW ,Ware JH ,Bertrand ME , et al. Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management: one-year results from the ACUITY trial. JAMA 2007;298:2497-2506
CrossRef | Web of Science | Medline
- Citing Articles (72)
Citing Articles
1
2012. References. , 348-358.
CrossRef2
Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting, Alice K. Jacobs, Jeffrey L. Anderson, Nancy Albert, Mark A. Creager, Steven M. Ettinger, Robert A. Guyton, Jonathan L. Halperin, Judith S. Hochman, Frederick G. Kushner, E. Magnus Ohman, William Stevenson, Clyde W. Yancy. (2012) 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: Executive Summary. Catheterization and Cardiovascular Interventions 79:3, 453-495
CrossRef3
Bernardo Cortese, Antonino Pitì. (2012) Bivalirudin has its own shelf in the cath lab, eventually. International Journal of Cardiology
CrossRef4
Mohamed Abdel-Wahab, Gert Richardt. (2012) Safety of bivalirudin in patients with coronary artery disease. Expert Opinion on Drug Safety 11:1, 141-150
CrossRef5
J. W. Yau, A. R. Stafford, P. Liao, J. C. Fredenburgh, R. Roberts, J. I. Weitz. (2011) Mechanism of catheter thrombosis: comparison of the antithrombotic activities of fondaparinux, enoxaparin, and heparin in vitro and in vivo. Blood 118:25, 6667-6674
CrossRef6
Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting. (2011) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary. Journal of the American College of Cardiology 58:24, 2550-2583
CrossRef7
Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting. (2011) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. Journal of the American College of Cardiology 58:24, e44-e122
CrossRef8
Kastrati, Adnan, Neumann, Franz-Josef, Schulz, Stefanie, Massberg, Steffen, Byrne, Robert A., Ferenc, Miroslaw, Laugwitz, Karl-Ludwig, Pache, Jürgen, Ott, Ilka, Hausleiter, Jörg, Seyfarth, Melchior, Gick, Michael, Antoniucci, David, Schömig, Albert, Berger, Peter B., Mehilli, Julinda, . (2011) Abciximab and Heparin versus Bivalirudin for Non–ST-Elevation Myocardial Infarction. New England Journal of Medicine 365:21, 1980-1989
Full Text9
Luo Chu-fan, Wu Xing, Hu Xun, Wu Gui-fu, Hu Cheng-heng, Du Zhi-min. (2011) Protective effect of lipid microspheres 1 on myocardial injury following elective percutaneous coronary intervention in patients with angina pectoris. Journal of Cardiovascular Medicine 12:11, 790-794
CrossRef10
Zenon Huczek, Krzysztof J. Filipiak, Janusz Kochman, Marcin Michalak, Marek Roik, Marcin Grabowski, Grzegorz Opolski. (2011) Medium on-treatment platelet reactivity to ADP is favorable in patients with acute coronary syndromes undergoing coronary stenting. Platelets 22:7, 521-529
CrossRef11
PHILIPP GEISBÜSCH, BARRY T. KATZEN, CONSTANTINO PEÑA, JAMES F. BENENATI, HEIKO UTHOFF. (2011) Bivalirudin Used as Alternative Anticoagulant in Carotid Artery Stenting: A Single Center Observational Study. Journal of Interventional Cardiologyno-no
CrossRef12
Stefanie Schulz, Julinda Mehilli, Gjin Ndrepepa, Franz Dotzer, Michael Dommasch, Sebastian Kufner, Kathrin A. Birkmeier, Klaus Tiroch, Robert A. Byrne, Albert Schömig, Adnan Kastrati. (2011) Influence of abciximab on evolution of left ventricular function in patients with non-ST-segment elevation acute coronary syndromes undergoing PCI after clopidogrel pretreatment: lessons from the ISAR-REACT 2 trial. Clinical Research in Cardiology 100:8, 691-699
CrossRef13
Ahmed A. Khattab, Gjin Ndrepepa, Stefanie Schulz, Franz-Josef Neumann, Julinda Mehilli, Heinz Joachim Büttner, Jürgen Pache, Melchior Seyfarth, Josef Dirschinger, Adnan Kastrati, Peter B. Berger, Albert Schömig, Gert Richardt. (2011) Statin effect on thrombin inhibitor effectiveness during percutaneous coronary intervention: a post-hoc analysis from the ISAR-REACT 3 trial. Clinical Research in Cardiology 100:7, 579-585
CrossRef14
Harold L. Dauerman, Sunil V. Rao, Frederic S. Resnic, Robert J. Applegate. (2011) Bleeding Avoidance Strategies. Journal of the American College of Cardiology 58:1, 1-10
CrossRef15
Osmar Antonio Centurión. (2011) Bivalirudin in Contemporary Percutaneous Coronary Intervention for Non-ST-Segment Elevation Acute Coronary Syndromes. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 10:2, 87-92
CrossRef16
Lynette R. Moser, Carrie W. Nemerovski, Kelley L. Good. (2011) Use of Prolonged Bivalirudin Infusions Following Percutaneous Coronary Intervention. Cardiovascular Drugs and Therapy 25:3, 267-276
CrossRef17
Andrew J Howe, James A Shand, Ian BA Menown. (2011) Advances in cardiology: clinical trial update. Future Cardiology 7:3, 299-310
CrossRef18
Stefano Savonitto, Nuccia Morici. (2011) Bivalirudina como anticoagulante durante intervenciones coronarias percutáneas en síndromes coronarios agudos: fortalezas y dudas. Revista Española de Cardiología 64:5, 361-364
CrossRef19
Charles Brown, Brijen Joshi, Nauder Faraday, Ashish Shah, David Yuh, Jeffrey J. Rade, Charles W. Hogue. (2011) Emergency Cardiac Surgery in Patients with Acute Coronary Syndromes. Anesthesia & Analgesia 112:4, 777-799
CrossRef20
L. Rössig, S. Genth-Zotz, M. Rau, G.R. Heyndrickx, T. Schneider, D.C.L. Gulba, M. Desaga, M. Buerke, S. Harder, A.M. Zeiher. (2011) Argatroban for elective percutaneous coronary intervention: The ARG-E04 multi-center study. International Journal of Cardiology 148:2, 214-219
CrossRef21
J.-P. Kevorkian. (2011) Les grands essais thérapeutiques présentés à l’ESC. Archives des Maladies du Coeur et des Vaisseaux - Pratique 2011, S21-S28
CrossRef22
Freek W.A. Verheugt, Steven R. Steinhubl, Martial Hamon, Harald Darius, Philippe Gabriel Steg, Marco Valgimigli, Steven P. Marso, Sunil V. Rao, Anthony H. Gershlick, A. Michael Lincoff, Roxana Mehran, Gregg W. Stone. (2011) Incidence, Prognostic Impact, and Influence of Antithrombotic Therapy on Access and Nonaccess Site Bleeding in Percutaneous Coronary Intervention. JACC: Cardiovascular Interventions 4:2, 191-197
CrossRef23
Maki Kato, Atsushi Kotoda, Tetsu Akimoto, Hideaki Takahashi, Shigeaki Muto, Eiji Kusano. (2011) Argatroban as a substitute for heparin during PTA for stenotic arteriovenous fistula. Nihon Toseki Igakkai Zasshi 44:2, 169-172
CrossRef24
J. Jaitner, J. Stegherr, T. Morath, S. Braun, I. Bernlochner, A. Schömig, A. Kastrati, D. Sibbing. (2011) Stability of the high on-treatment platelet reactivity phenotype over time in clopidogrel-treated patients. Thrombosis and Haemostasis 105:1, 107-112
CrossRef25
Dongmei Zhang, Zining Wang, Xia Zhao, Wei Lu, Jingkai Gu, Yimin Cui. (2011) Pharmacokinetics, Pharmacodynamics, Tolerability and Safety of Single Doses of Bivalirudin in Healthy Chinese Subjects. Biological & Pharmaceutical Bulletin 34:12, 1841-1848
CrossRef26
Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting, Alice K. Jacobs, Jeffrey L. Anderson, Nancy Albert, Mark A. Creager, Steven M. Ettinger, Robert A. Guyton, Jonathan L. Halperin, Judith S. Hochman, Frederick G. Kushner, E. Magnus Ohman, William Stevenson, Clyde W. Yancy. (2011) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. Catheterization and Cardiovascular Interventionsn/a-n/a
CrossRef27
Eugenio Stabile, Giovanni Sorropago, Tullio Tesorio, Grigore Popusoi, Vittorio Ambrosini, Maria Teresa Mottola, Giancarlo Biamino, Paolo Rubino. (2010) Heparin versus bivalirudin for carotid artery stenting using proximal endovascular clamping for neuroprotection: Results from a prospective randomized study. Journal of Vascular Surgery 52:6, 1505-1510
CrossRef28
David A Van De Car, Sunil V Rao, E Magnus Ohman. (2010) Bivalirudin: a review of the pharmacology and clinical application. Expert Review of Cardiovascular Therapy 8:12, 1673-1681
CrossRef29
Matthias Lenski, Felix Mahfoud, Christian Werner, Axel Bauer, Michael Böhm. (2010) Hotline sessions and clinical trial updates presented at the European Society of Cardiology Congress in Stockholm 2010. Clinical Research in Cardiology 99:11, 679-692
CrossRef30
Venkatesan D. Vidi, Michael E. Matheny, Vikram Agarwal, Nipun Arora, Sharon Donnelly, Sripal Bangalore, Frederic S. Resnic. (2010) Validation of Long-Term Benefits of Bivalirudin Versus Unfractionated Heparin in Routine Clinical Practice After Percutaneous Coronary Intervention. The American Journal of Cardiology 106:9, 1234-1240
CrossRef31
H. M. Nef, H. Mollmann, C. W. Hamm. (2010) Anticoagulation in percutaneous coronary interventions: no man's land?. European Heart Journal 31:20, 2447-2448
CrossRef32
S. Schulz, J. Mehilli, F.-J. Neumann, T. Schuster, S. Massberg, C. Valina, M. Seyfarth, J. Pache, K.-L. Laugwitz, H.-J. Buttner, G. Ndrepepa, A. Schomig, A. Kastrati, . (2010) ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention. European Heart Journal 31:20, 2482-2491
CrossRef33
Zafar Iqbal, Marc Cohen. (2010) Emerging antithrombotic agents: what does the intensivist need to know?. Current Opinion in Critical Care 16:5, 419-425
CrossRef34
John J. Lopez, Michelle J. Keyes, Sandeep Nathan, Robert Piana, Michael Pencina, Gaurav Dhar, Steven Marso, Sunil Rao, Salim Shammo, Walt Marquardt, David J. Cohen, Neal S. Kleiman. (2010) Rapid adoption of drug-eluting stents: Clinical practices and outcomes from the early drug-eluting stent era. American Heart Journal 160:4, 767-774.e1
CrossRef35
Leo Bossaert, Robert E. O’Connor, Hans-Richard Arntz, Steven C. Brooks, Deborah Diercks, Gilson Feitosa-Filho, Jerry P. Nolan, Terry L. Vanden Hoek, Darren L. Walters, Aaron Wong, Michelle Welsford, Karen Woolfrey. (2010) Part 9: Acute coronary syndromes. Resuscitation 81:1, e175-e212
CrossRef36
Brian P O’Neill, Eric Scot Shaw, Mauricio G Cohen. (2010) Anticoagulation in percutaneous coronary intervention. Interventional Cardiology 2:4, 559-577
CrossRef37
Jorge F. Saucedo. (2010) Balancing the benefits and risks of antiplatelet agents in patients with non-ST-segment elevated acute coronary syndromes and undergoing percutaneous coronary intervention. Journal of Thrombosis and Thrombolysis 30:2, 200-209
CrossRef38
Bernardo Cortese. (2010) A comment on laboratory monitoring of new anticoagulants. American Journal of Hematology 85:7, 546-546
CrossRef39
Gjin Ndrepepa, Dritan Keta, Stefanie Schulz, Julinda Mehilli, Anette Birkmeier, Franz-Josef Neumann, Albert Schömig, Adnan Kastrati. (2010) Characterization of patients with bleeding complications who are at increased risk of death after percutaneous coronary intervention. Heart and Vessels 25:4, 294-298
CrossRef40
CEDRIC DELHAYE, KOHEI WAKABAYASHI, GABRIEL MALUENDA, ITSIK BEN-DOR, REBECCA TORGUSON, ZHENYI XUE, WILLIAM O. SUDDATH, LOWELL F. SATLER, AUGUSTO D. PICHARD, KENNETH M. KENT, JOSEPH LINDSAY, RON WAKSMAN. (2010) Safety and Efficacy of Bivalirudin for Percutaneous Coronary Intervention with Rotational Atherectomy. Journal of Interventional Cardiology 23:3, 223-229
CrossRef41
Cédric Delhaye, Kohei Wakabayashi, Gabriel Maluenda, Loic Belle, Itsik Ben-Dor, Manuel A. Gonzalez, Michael A. Gaglia, Rebecca Torguson, Zhenyi Xue, William O. Suddath, Lowell F. Satler, Kenneth M. Kent, Joseph Lindsay, Augusto D. Pichard, Ron Waksman. (2010) Body mass index and bleeding complications after percutaneous coronary intervention: Does bivalirudin make a difference?. American Heart Journal 159:6, 1139-1146
CrossRef42
Renato D. Lopes, Eric D. Peterson, Anita Y. Chen, Matthew T. Roe, Tracy Y. Wang, E. Magnus Ohman, David J. Magid, P. Michael Ho, Stephen D. Wiviott, Benjamin M. Scirica, Karen P. Alexander. (2010) Antithrombotic Strategy in Non–ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention. JACC: Cardiovascular Interventions 3:6, 669-677
CrossRef43
JAE-JIN KWAK, HUI-NAM PAK, JIN-KUN JANG, SOOK KYOUNG KIM, JAE HYUNG PARK, JONG-IL CHOI, CHUN HWANG, YOUNG-HOON KIM. (2010) Safety and Convenience of Continuous Warfarin Strategy During the Periprocedural Period in Patients Who Underwent Catheter Ablation of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology 21:6, 620-625
CrossRef44
Jeffrey Brinker. (2010) The Score Is in but Is the Decision Final?
Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.. Journal of the American College of Cardiology 55:23, 2567-2569
CrossRef45
Guido Parodi, Angela Migliorini, Renato Valenti, Benedetta Bellandi, Umberto Signorini, Guia Moschi, Piergiovanni Buonamici, Giampaolo Cerisano, David Antoniucci. (2010) Comparison of Bivalirudin and Unfractionated Heparin Plus Protamine in Patients With Coronary Heart Disease Undergoing Percutaneous Coronary Intervention (from the Antithrombotic Regimens aNd Outcome [ARNO] Trial). The American Journal of Cardiology 105:8, 1053-1059
CrossRef46
S. S. Jolly, S. Yusuf. (2010) Which antithrombotic to use during PCI?. European Heart Journal 31:5, 522-524
CrossRef47
S. Schulz, J. Mehilli, G. Ndrepepa, F.-J. Neumann, K. A. Birkmeier, S. Kufner, G. Richardt, P. B. Berger, A. Schomig, A. Kastrati, . (2010) Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial. European Heart Journal 31:5, 582-587
CrossRef48
Veronica HT Chan, Paul Monagle, Patti Massicotte, Anthony KC Chan. (2010) Novel paediatric anticoagulants: a review of the current literature. Blood Coagulation & Fibrinolysis 21:2, 144-151
CrossRef49
J. A. Rassen, M. A. Mittleman, R. J. Glynn, M. Alan Brookhart, S. Schneeweiss. (2010) Safety and effectiveness of bivalirudin in routine care of patients undergoing percutaneous coronary intervention. European Heart Journal 31:5, 561-572
CrossRef50
D. SIBBING, S. SCHULZ, S. BRAUN, T. MORATH, J. STEGHERR, J. MEHILLI, A. SCHÖMIG, N. VON BECKERATH, A. KASTRATI. (2010) Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. Journal of Thrombosis and Haemostasis 8:2, 250-256
CrossRef51
Marc Cohen. (2010) The Thrombin Hypothesis in ACS: A Disappointing Disconnect between Bench Data and Bedside Clinical Trials. The American Journal of Medicine 123:2, 103-110
CrossRef52
Cedric Delhaye, Gabriel Maluenda, Kohei Wakabayashi, Itsik Ben-Dor, Sara D. Collins, Asmir I. Syed, Manuel A. Gonzalez, Michael A. Gaglia, Rebecca Torguson, Zhenyi Xue, William O. Suddath, Lowell F. Satler, Kenneth M. Kent, Joseph Lindsay, Augusto D. Pichard, Ron Waksman. (2010) Safety and In-Hospital Outcomes of Bivalirudin Use in Dialysis Patients Undergoing Percutaneous Coronary Intervention. The American Journal of Cardiology 105:3, 297-301
CrossRef53
Gjin Ndrepepa, Stefanie Schulz, Dritan Keta, Julinda Mehilli, Anette Birkmeier, Steffen Massberg, Karl-Ludwig Laugwitz, Franz-Josef Neumann, Melchior Seyfarth, Peter B. Berger, Albert Schömig, Adnan Kastrati. (2010) Bleeding After Percutaneous Coronary Intervention With Bivalirudin or Unfractionated Heparin and One-Year Mortality. The American Journal of Cardiology 105:2, 163-167
CrossRef54
Chiara Melloni, Ian Fier, James Roach, Andrzej S. Kosinski, Samuel Broderick, Kristina Sigmon, Shelley Myles, Richard C. Becker, Sunil V. Rao. (2009) Design and rationale of the Evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) trial. American Heart Journal 158:5, 726-733
CrossRef55
Jason B. Lindsey, Steven P. Marso, Michael Pencina, Joshua M. Stolker, Kevin F. Kennedy, Charanjit Rihal, Greg Barsness, Robert N. Piana, Steven L. Goldberg, Donald E. Cutlip, Neal S. Kleiman, David J. Cohen. (2009) Prognostic Impact of Periprocedural Bleeding and Myocardial Infarction After Percutaneous Coronary Intervention in Unselected Patients. JACC: Cardiovascular Interventions 2:11, 1074-1082
CrossRef56
Mark Y. Chan, Jeffrey I. Weitz, Yahye Merhi, Robert A. Harrington, Richard C. Becker. (2009) Catheter thrombosis and percutaneous coronary intervention: fundamental perspectives on blood, artificial surfaces and antithrombotic drugs. Journal of Thrombosis and Thrombolysis 28:3, 366-380
CrossRef57
Robert P. Giugliano, Eugene Braunwald. (2009) The Year in Non–ST-Segment Elevation Acute Coronary Syndrome. Journal of the American College of Cardiology 54:16, 1544-1555
CrossRef58
Bernardo Cortese, Andrea Picchi, Andrea Micheli, Alberto Genovesi Ebert, Francesca Parri, Silva Severi, Ugo Limbruno. (2009) Comparison of Prolonged Bivalirudin Infusion Versus Intraprocedural in Preventing Myocardial Damage After Percutaneous Coronary Intervention in Patients With Angina Pectoris. The American Journal of Cardiology 104:8, 1063-1068
CrossRef59
Gilles Lemesle, Axel De Labriolle, Laurent Bonello, Asmir Syed, Sara Collins, Gabriel Maluenda, Rebecca Torguson, Kimberly Kaneshige, Zhenyi Xue, William O. Suddath, Lowell F. Satler, Kenneth M. Kent, Joseph Lindsay, Augusto D. Pichard, Ron Waksman. (2009) Impact of bivalirudin on in-hospital bleeding and six-month outcomes in octogenarians undergoing percutaneous coronary intervention. Catheterization and Cardiovascular Interventions 74:3, 428-435
CrossRef60
R. B. Eslam, N. Reiter, A. Kaider, S. Eichinger, I. M. Lang, S. Panzer. (2009) Regulation of PAR-1 in patients undergoing percutaneous coronary intervention: effects of unfractionated heparin and bivalirudin. European Heart Journal 30:15, 1831-1836
CrossRef61
Michael Ray, Manjeet Juneja, Nicholas Bett, Darren Walters. (2009) A comparison of anticoagulation with bivalirudin and provisional GPIIb/IIIa inhibition with unfractionated heparin and mandatory GPIIb/IIIa inhibition during percutaneous coronary intervention in relation to platelet activation and the inhibition of coagulation. EuroIntervention 5:3, 330-335
CrossRef62
Jan Steffel, Thomas F Lüscher. (2009) Novel anticoagulants in clinical development: focus on factor Xa and direct thrombin inhibitors. Journal of Cardiovascular Medicine 10:8, 616-623
CrossRef63
R. E. G. SCHUTGENS, A. TUINENBURG, G. ROOSENDAAL, S. Hoseyni GUYOMI, E. P. MAUSER-BUNSCHOTEN. (2009) Treatment of ischaemic heart disease in haemophilia patients: an institutional guideline. Haemophilia 15:4, 952-958
CrossRef64
Simon R. Dixon, Cindy L. Grines, William W. O'Neill. (2009) The Year in Interventional Cardiology. Journal of the American College of Cardiology 53:22, 2080-2097
CrossRef65
Brendan J. Doyle, Charanjit S. Rihal, Dennis A. Gastineau, David R. Holmes. (2009) Bleeding, Blood Transfusion, and Increased Mortality After Percutaneous Coronary Intervention. Journal of the American College of Cardiology 53:22, 2019-2027
CrossRef66
Renato D. Lopes, Karen P. Alexander, Steven V. Manoukian, Michel E. Bertrand, Frederick Feit, Harvey D. White, Charles V. Pollack, James Hoekstra, Bernard J. Gersh, Gregg W. Stone, E. Magnus Ohman. (2009) Advanced Age, Antithrombotic Strategy, and Bleeding in Non–ST-Segment Elevation Acute Coronary Syndromes. Journal of the American College of Cardiology 53:12, 1021-1030
CrossRef67
Harvey D White. (2009) HORIZONS trial: a step forward for primary percutaneous coronary intervention. Expert Review of Cardiovascular Therapy 7:2, 125-129
CrossRef68
GILLES LEMESLE, LAURENT BONELLO, AXEL DE LABRIOLLE, DANIEL H. STEINBERG, PROBAL ROY, TINA L. PINTO SLOTTOW, REBECCA TORGUSON, KIMBERLY KANESHIGE, ZHENYI XUE, WILLIAM O. SUDDATH, LOWELL F. SATLER, KENNETH M. KENT, JOSEPH LINDSAY, AUGUSTO D. PICHARD, RON WAKSMAN. (2009) Impact of Bivalirudin Use on Outcomes in Nonagenarians Undergoing Percutaneous Coronary Intervention. Journal of Interventional Cardiology 22:1, 61-67
CrossRef69
Stefano Savonitto, Nuccia Morici, Alice Sacco, Silvio Klugmann. (2009) Target populations and relevant therapeutic end points to further improve outcomes in NSTEACS patients. Future Cardiology 5:1, 27-41
CrossRef70
Owayed M. Al Shammeri, Richard Crowell, Keir Stewart, Stephen Fort. (2009) Failed pericardiocentesis for acute cardiac tamponade: Two cases associated with bivalirudin administration during PCI. Catheterization and Cardiovascular InterventionsNA-NA
CrossRef71
R. Iijima, G. Ndrepepa, J. Mehilli, R. A. Byrne, S. Schulz, F.-J. Neumann, G. Richardt, P. B. Berger, A. Schomig, A. Kastrati. (2008) Profile of bleeding and ischaemic complications with bivalirudin and unfractionated heparin after percutaneous coronary intervention. European Heart Journal 30:3, 290-296
CrossRef72
Robert P. Giugliano, Eugene Braunwald. (2008) The Year in Non–ST-Segment Elevation Acute Coronary Syndrome. Journal of the American College of Cardiology 52:13, 1095-1103
CrossRef
