Adjunctive Therapy


Principles     Archive 2001

TCT 2002 Abstracts 

ABC of antithrombotic therapy: Antithrombotic therapy in acute coronary syndromes
Robert D S Watson, Bernard S P Chin, and Gregory Y H Lip
BMJ 2002; 325: 1348-1351. [Full text] [PDF]  

PowerPoint Presentations:


Antiplatelet therapy overview     Archive 1989-2001

*Review*
Antiplatelet and anticoagulant therapy in elective percutaneous coronary intervention
Jurriėn M ten Berg, HW Thijs Plokker and Freek WA Verheugt
http://cvm.controlled-trials.com/content/2/3/129

Full text journal article Oct 2002
Combination Antiplatelet Therapy: Implications for Pharmacists
The following two case reports involving patients who received suboptimal antiplatelet therapy point out disparities between national guidelines and actual clinical practice that led to undesirable consequences in both patients.

Full text journal article Jul 2002
Preventing Subacute Thrombosis
Patients should continue to receive optimal medical care despite the costs or inconvenience of subacute thrombosis therapy.


Clopidogrel, ticlopidine, aspirin  Archive 1991-2001

Website
(Bristol-Myers Squibb/Sanofi Pharmaceuticals)
http://www.plavix.com/HCP/cardiology_index.jsp 

AHA 2002 Meeting Coverage 

CREDO 1-year results confirm benefit of long-term aspirin and clopidogrel therapy after PCI
Steinhubl SR, et al. 
JAMA 2002; 288:2411-2420.
with slides / Continuation of antiplatelet therapy with both aspirin and clopidogrel for 1 year, as opposed to the current standard of 2 to 4 weeks, leads to significant reductions in major thrombotic events among patients undergoing elective PCI. The results were presented to coincide with their publication in the Journal of the American Medical Association. 
American Heart Association Scientific Sessions 2002. [ Nov 18, 2002 ]

CREDO: Clopidogrel for the Reduction of Events During Observation - 1-year Follow-up Results
Following PCI, maintaining dual antiplatelet therapy with aspirin and clopidogrel for up to 1 year significantly reduces the risk of adverse thrombotic events by 26.9%.

TCT 2002 Abstracts 

The CREDO Trial S. R. Steinhubl

TCT 2002 Expert presentations

Integrating the Results of Clnical Trials with ACE Inhibitors/Angiotensin Receptor Blockers (HOPE) and Antiplatelet Agents (CURE) into Routine Clinical Practice S. Mehta  
CREDO Trial S. R. Steinhubl  

CREDO: Clopidogrel before elective PCI cuts 1-month event risk
with slide / Clopidogrel, which solidified a role as primary therapy for patients presenting with ACS in the recent CURE trial, appears to prevent thrombotic complications when given before elective PCI. Preliminary findings from a prospective, randomized trial showed that clopidogrel pretreatment, with or without GP IIb/IIIa inhibition, significantly reduced the 28-day clinical-event risk--as long as pretreatment lasted 6 to 24 hours. 

CREDO: Clopidogrel for Reduction of Events During Observation
Compared with placebo, the administration of clopidogrel 6 hours prior to PCI reduces the risk of death, MI, and TVR.

Safety of clopidogrel pre-bypass debated
Hongo et al, Khot et al. 
J Am Coll Cardiol 2002; 40: 231-237, 218-219. [ Jul 19, 2002 ]
Two articles question the routine administration of clopidogrel in ACS patients (recommended post-CURE) or before anticipated stent implantation, mainly due to increased bleeding risk in patients who go on to early CABG. However, their arguments are refuted by CURE investigators and another leading cardiologist. 

Clopidogrel benefit consistent in ACS across all risk groups
Budaj A et al. 
Circulation: published online before print September 24, 2002. 
with slides / The relative benefit of clopidogrel is consistent in low, intermittent and high-risk ACS patients, but the absolute benefit is still greatest in the higher risk patients. 

Antiplatelet effect of clopidogrel inhibited by atorvastatin 
Lau WC et al. 
Circulation 2002, published online before print November 25, 2002
http://www.theheart.org/documents/page.cfm?from=590001200&doc_id=33511
 
Clopidogrel appears to be activated by the same enzyme that metabolizes several of the lipophilic statins, suggesting that a hydrophilic statin may be preferable when the 2 agents are given together. As clopidogrel is now recommended for all ACS patients, this could have an important effect on the statin market. 
Atorvastatin Reduces the Ability of Clopidogrel to Inhibit Platelet Aggregation: A New Drug-Drug Interaction    
Wei C. Lau,  et al
Circulation 2003;107 32-37
http://circ.ahajournals.org/cgi/content/abstract/107/1/32?etoc

Full text journal article May 2002
Clopidogrel Treatment Before Percutaneous Coronary Intervention Reduces Adverse Cardiac Events
Concomitant administration of aspirin, clopidrogrel, enoxaparin and eptifibatide in ACS patients is safe and feasible.

Abstract
Ticlopidine versus oral anticoagulation for coronary stenting
A Cochrane Review Abstract: Evidence Based Medicine reviews based primarily on meta-analysis of controlled clinical trials.

Full text journal article May 2002
Safety and Efficacy of Only 2 Weeks of Ticlopidine Therapy in Patients at Increased Risk of
Coronary Stent Thrombosis: Results From the Antiplatelet Therapy

The risk of stent thrombosis and other adverse events in patients treated with ticlopidine for only 2 weeks is low.

Full text journal article Aug 2002
Take 2 Aspirin and Call Me in the Morning -- Cardiologists SHOULD Be Saying It!
Find out about aspirin“s properties, its efficacy compared with other agents, and new guidelines advocating its use.

Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting
Bhatt DL, et al.
J Am Coll Cardiol 2002;39:9-14
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11755280
Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment

Clopidogrel treatment before percutaneous coronary intervention reduces adverse cardiac events 
Berglund U, et al. 
J Invasive Cardiol 2002;14:243-6.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11983944
Clopidogrel treatment in addition to aspirin before PCI was associated with a reduction of in-hospital adverse cardiac events. It was also safe and cost-saving.

Comparison of antiplatelet effect of loading dose of clopidogrel versus abciximab during coronary intervention 
Claeys MJ, et al. 
Blood Coagul Fibrinolysis 2002;13:283-288.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12032392
A loading dose of 450 mg clopidogrel was found to be more effective than the standard loading dose of 375 mg. Platelet aggregation during coronary intervention is strongly inhibited by both abciximab and by high loading dose of clopidogrel. Although abciximab showed a stronger antiplatelet effect than clopidogrel, it remains to be established whether this ex vivo superiority of abciximab also translates into an overall clinical benefit in patients with elective stent implantation.

The thienopyridines 
Lubbe DF, et al. 
J Interv Cardiol 2002;15:85-93.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12053688
Widespread use of ticlopidine, the first available thienopyridine, was limited by frequent side-effects, including life-threatening neutropenia and thrombotic thrombocytopenic purpura. Following the introduction of clopidogrel, a thienopyridine with an excellent safety profile, dual antiplatelet therapy with aspirin and clopidogrel has become standard therapy following coronary stent implantation and coronary VBT. In patients presenting with ACS, the addition of clopidogrel to aspirin has now been proven to reduce ischemic events. The most important limitation of dual antiplatelet therapy is the increased bleeding risk as compared with aspirin alone, particularly in patients undergoing coronary artery bypass grafting during the index hospitalization. However, for many patients with ACS, combination therapy is appropriate.

Use of clopidogrel loading, enoxaparin, and double-bolus eptifibatide in the setting of early percutaneous coronary intervention for acute coronary syndromes 
Miller L, et al. 
J Invasive Cardiol 2002;14:247-50.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11983945
Patients received aspirin 325 mg orally, clopidogrel 300 mg orally, enoxaparin 0.5 mg/kg intravenous (IV), and eptifibatide using the ESPIRIT dosing (180 g/kg bolus IV, immediately followed by a 2 g/kg/minute continuous IV infusion, and then a second 180 g/kg bolus IV ten minutes after the first bolus).
This pilot study demonstrates the feasibility of administering aspirin, clopidogrel, enoxaparin, and eptifibatide in the setting of percutaneous coronary intervention for acute coronary syndromes. These agents can be administered moments before the coronary intervention with no apparent compromise in patient safety.

Effect of 300- and 450-mg clopidogrel loading doses on membrane and soluble P-selectin in patients undergoing coronary stent implantation 
Seyfarth HJ, et al. 
Am Heart J 2002;143:118-23.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11773921

http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a119372&target=
In our study the application of 450 mg of clopidogrel as the loading dose in patients undergoing coronary stenting shortens the period until the maximum effect of the ADP receptor antagonist is achieved and thus may lead to a more successful prevention of subacute coronary stent thromboses.

Full text journal article Ago 2002
Randomized Comparison of Cilostazol Versus Ticlopidine Hydrochloride for Antiplatelet Therapy After
Coronary Stent Implantation for Prevention of Late Restenosis

Aspirin plus cilostazol therapy may be effective for the prevention of not only stent thrombosis but also restenosis

When increased therapeutic benefit comes at increased cost 
Wood AJ. 
N Engl J Med 2002;346:1819-21.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12050345

http://content.nejm.org/cgi/content/full/346/23/1819

What is the optimum dose of aspirin for secondary prevention?
The question of what the optimum dose of aspirin is for the secondary prevention of heart disease has been highlighted by an argument over this issue between two drug companies. However, two researchers, who have both conducted studies recently in this area, were in agreement that lower doses of aspirin (between 75-150 mg) seemed equally effective in preventing recurrent cardiovascular events than higher doses, and would probably result in less gastric side effects. [ May 02, 2002 ]


GP IIb/IIIa Inhibitors    

GP IIb-IIIa Overview    Archive 2000-2001

GP IIb-IIIa use in PCI - Free PowerPoint Slides
http://www.clinicaltrialresults.org/ua/interventional/pci_home.htm 

TCT 2002 Meeting Coverage

Universal vs. Selective Use of IIb-IIIa- Inhibitors During PCI R. Califf
R. E. Kuntz

Universal vs Selective Use of Glycoprotein IIb/IIIa Inhibitors During Percutaneous Intervention
World-renowned experts discuss the role of GP IIb/IIIa inhibitors in the cath lab and whether the drugs should be used in all ACS patients.

TCT 2002 Expert Presentations

Platelet Glycoprotein IIb/IIIa Inhibitors in ACS and PCI J. E. Tcheng  

TCT 2002 DEBATE: Do GP IIB/IIIA Inhibitors Reduce Mortality When Used in PCI?

TCT 2002 Debates Expert presentations

Universal vs. Selective Use of Glycoprotein IIb/IIIa Inhibitors During Percutaneous Intervention

Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials 
Boersma E, et al. 
Lancet 2002;359:189-98.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11812552
Summary:

IIb/IIIa Inhibitors In ACS: A Meta-Analysis Of All Major Randomised Clinical Trials E. Boersma   Lancet 2002; 359: 189-98  

Full text journal article Jul 2002
Administration of Glycoprotein IIb-IIIA Inhibitors in Patients with ST-Segment Elevation Myocardial Infarction
Why is reperfusion therapy, either by mechanical or pharmacological means, required immediately by these patients?

Full text journal article Sep 2002
Integrating GP IIb/IIIa Inhibition into Treatment Strategies for Acute ST-Elevation Myocardial Infarction
Against the background of established clinical benefit in non-ST segment elevation acute coronary syndromes (ACS) and elective percutaneous revascularization, recent trials examining the role of glycoprotein (GP) IIb/IIIa inhibition in acute myocardial infarction (AMI) have been based on the rationale that effective platelet inhibition is fundamental to reperfusion strategies designed to restore myocardial perfusion, limit infarct size, and improve survival.

CME Circle Jul 2002
Diabetes and Cardiovascular Disease: The Role of the Glycoprotein IIb/IIIa Inhibitors  CME
Up to 25% of patients referred for percutaneous coronary interventions or revascularization have diabetes mellitus. Emerging evidence of the extraordinary benefits of glycoprotein IIb/IIIa inhibitors in this patient population is providing hope for more effective treatment options and improved prognosis for patients coping with the cardiovascular complications of diabetes.

Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary interventions
E. Karvouni, D.G. Katritsis, J.P.A. Ioannidis
J Am Coll Cardiol 2003;41:26-32
Full text via ScienceDirect :
http://www.sciencedirect.com/science?_ob=GatewayURL&_origin=CONTENTS&_method=
citationSearch&_piikey=S0735109702026669&_version=1&md5=e0b5f8e686b8a026ea4248841cb257fa
In patients undergoing PCI, GP IIb/IIIa receptor antagonists confer a significant and sustained decrease (20% to 30%) in the risk of death. 

Editorials
Platelet Glycoprotein IIb/IIIa Inhibition and Atheroembolism During Bypass Graft Angioplasty: A Cup Half Full    
Dean J. Kereiakes
Circulation 2002;106 2994-2996
http://circ.ahajournals.org/cgi/content/full/106/24/2994?etoc 

Lack of Benefit From Intravenous Platelet Glycoprotein IIb/IIIa Receptor Inhibition as Adjunctive Treatment for Percutaneous Interventions of Aortocoronary Bypass Grafts: A Pooled Analysis of Five Randomized Clinical Trials    
Marco Roffi et al
Circulation 2002;106 3063-3067
http://circ.ahajournals.org/cgi/content/abstract/106/24/3063?etoc
Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.

Gender differences in clinical outcome after coronary artery stenting with use of glycoprotein IIb/IIIa inhibitors 
Iakovou I, et al. 
Am J Cardiol 2002;89:976-9.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11950440

Summaries of important articles from major peer-reviewed journals

TARGET Follow-Up Study D. J. Moliterno   Lancet 2002; 360: 355-60  

6-month TARGET results published
TARGET investigators
Lancet 2002;360:355-360. [ Aug 01, 2002 ]
Although 6-month results show similar event rates for tirofiban and abciximab in stent patients, abciximab remains the drug of choice because of its early benefit.


Abciximab    Archive 1993-2001

ReoPro Trials - Free PowerPoint Slides
http://www.clinicaltrialresults.org/ua/abciximab/abciximab_home.htm 

ReoPro.com
http://www.reopro.com/
Web site with many resources: Science of ReoPro, Clinical trials, Multimedia cases, Clinical experiences, Mini lectures, Speaker slides in PowerPoint format, CME, Medical meetings
Access: No registration required

TCT 2002 Meeting Coverage

Assay-guided abciximab bolus dosing worked, saved money in registry study
Giving only 70% of the standard abciximab bolus before PCI, as long as a rapid assay says platelet suppression is adequate, is safe and effective as well as cheaper overall, according to a prospective registry analysis. 
Transcatheter Cardiovascular Therapeutics 2002. [ Oct 03, 2002 ]

Full text journal article Aug 2002
Educational Program to Reduce Major Bleeding in Patients Undergoing Percutaneous
Coronary Interventions and Receiving Abciximab

Abciximab is a potent antiplate let agent that has been shown to significantly reduce ischemic complications in patients undergoing percutaneous coronary intervention (PCI).

Full text journal article Jan 2002
Prophylactic Abciximab in Elective Coronary Stenting: Results of a Randomized Trial
Abciximab does not increase the rate of complications as compared to standard adjuvant therapy.

Full text journal article Feb 2002
Abciximab Improves 6-Month Clinical Outcome After Rescue Coronary Angioplasty
Abciximab during rescue PTCA positively affects clinical outcome at 6 months.

Full text journal article Mar 2002
Potential Anaphylactic Shock With Abciximab Readministration
This case demonstrates that anaphylaxis can occur with readministration, even after standard allergy prophylaxis.

Full text journal article Aug 2002
Abciximab Therapy Improves 1-Month Survival Rate in Unselected Patients With Acute
Myocardial Infarction Undergoing Routine Infarct Artery Stent Implantation

This study supports the use of abciximab therapy in nonselected patients with AMI undergoing routine IRA stent implantation.

Full text journal article Apr 2002
Glycoprotein IIb-IIIa Inhibition with Abciximab and Postprocedural Risk Assessment: Lessons
From the Evalution of Platelet IIb/IIIa Inhibitor for Stenting Trial and Implication for Ad Hoc Use of Glycoprotein IIb-IIIa Antagonists

IIb/IIIa antagonism with abciximab is equally effective in reducing events regardless of degree of risk after stenting.

Platelet Glycoprotein IIb/IIIa Inhibitor Use During Percutaneous Coronary Intervention: IIb or Not IIb, What is the Question? 
Young JJ, et al. 
J Invasive Cardiol 2002;14:404-10.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12082194
 
Currently, small molecule GP IIb/IIIa inhibitor, tirofiban (Aggrastat, Merck & Company), which (similar to eptifibatide) is approved for the medical therapy of patients with non-ST segment elevation acute coronary syndromes (ACS), has not received indication for use in the PCI setting. Although the clinical benefits of both abciximab and eptifibatide administered at the time of PCI have been proven in randomized clinical trials, only abciximab has demonstrated a late survival advantage in patients following PCI. Evidence in support of the presence, magnitude and possible mechanisms for abciximab survival advantage is herein reviewed.

Reduced inhibition by abciximab in platelets with the PlA2 polymorphism 
Wheeler GL, et al. 
Am Heart J 2002;143:76-82.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11773915

http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a119763&target=
 
PlA1/A2 platelets are less completely inhibited with abciximab, contributing to the observed interindividual variability in platelet function inhibition. Because the extent of platelet inhibition is an independent predictor for the risk of major adverse coronary events after percutaneous coronary intervention, the relative resistance of PlA2-positive platelets may contribute to a less favorable outcome in these patients.

Facilitated percutaneous intervention following combination therapy with reteplase and abciximab for acute myocardial infarction 
Weinstock BS. 
J Invasive Cardiol 2002;14:100-4; quiz 104-5.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11818648

Diabetic patients treated with abciximab and intracoronary stenting 
Walton BL, et al. 
Catheter Cardiovasc Interv 2002;55:321-5.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11870935
The trends toward improvement of mortality, surgical or percutaneous revascularization, and cardiac readmissions suggest the effect of abciximab may provide benefit for up to 9 months for higher-risk diabetic patients.

Bleeding Complications of Platelet Glycoprotein IIb/IIIa Inhibitor Abciximab (ReoPro ) 
Trivedi SM, et al. 
J Invasive Cardiol 2002;14:423-5.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12082199
Studies of patients scheduled for percutaneous coronary intervention with acute coronary syndrome have shown that the addition of intravenous glycoprotein (GP) IIb/IIIa inhibitors to aspirin and heparin is associated with a reduction in death or myocardial infarction compared to therapy with aspirin and heparin alone. The principle safety issue with GP IIb/IIIa inhibitors is the risk of bleeding, as the potent antiplatelet effect of these drugs may adversely affect hemostasis. In addition, antagonists of GP IIb/IIIa may increase the risk of thrombocytopenia. This is a case report of abciximab-induced severe thrombocytopenia which led to fatal intra-cranial hemorrhage.

Guidelines for acute coronary syndrome without ST elevation 
Toquero Ramos J, et al. 

Lancet 2002;359:1349; discussion 1350.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11965311

Prophylactic abciximab in elective coronary stenting: results of a randomized trial 
Tamburino C, et al. 
J Invasive Cardiol 2002;14:72-9.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11818641
The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting.

Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction 
Stone GW, et al. 
N Engl J Med 2002;346:957-66.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11919304

http://content.nejm.org/cgi/content/full/346/13/957

http://content.nejm.org/cgi/content/abstract/346/13/957
At experienced centers, stent implantation (with or without abciximab therapy) should be considered the routine reperfusion strategy.

Combined glycoprotein IIb/IIIa receptor inhibition and low-dose fibrinolysis for peripheral arterial thrombosis
Rocha-Singh KJ, et al. 
Catheter Cardiovasc Interv 2002;55:457-60.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11948891
The simultaneous intra-arterial administration of abciximab in conjunction with low-dose reteplase (< or = 0.5 U/hr) was safe in 13 patients; 2 patients experienced major hemorrhagic complication at a reteplase dose of 1 U/hr. The primary success rate was 100%; all patients experienced an excellent clinical response with no clinical evidence of distal embolization. No patient required repeat endovascular or surgical revascularization during mean follow-up of 9.3 months. This promising new thrombolytic strategy for the treatment of peripheral arterial occlusive disease requires further study.

Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization 
Ray KK. 
Circulation 2002;105:e74.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11914269

http://www.circulationaha.org/cgi/content/full/105/12/e74

Abciximab improves 6-month clinical outcome after rescue coronary angioplasty 
Petronio AS, et al. 
Am Heart J 2002;143:334-41.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11835040

http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a119762&target=
Treatment with abciximab during rescue PTCA positively affects clinical outcome at 6-month follow-up without increasing periprocedural bleeding.

Determination of platelet aggregation inhibition during percutaneous coronary intervention with the platelet function analyzer PFA-100 
Madan M, et al. 
Am Heart J 2002;144:151-8.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12094202

http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a123581&target=
PFA-100 is a rapid simple assay used as a means of assessing inhibition of platelet aggregation during PCI performed with glycoprotein IIb/IIIa inhibition. The platelet function analyzer PFA-100 (Dade-Behring, Deerfield, Ill) measures platelet function by determining the time to occlusion of an aperture in a biochemically active membrane as whole blood flows under high shear conditions. Failure to achieve nonclosure early after the initiation of abciximab therapy warrants further investigation because there may be an association with adverse cardiac events at 6-month follow-up.

Clinical Pharmacokinetics of Tirofiban, a Nonpeptide Glycoprotein IIb/IIIa Receptor Antagonist: Comparison with the Monoclonal Antibody Abciximab 
Kondo K, et al. 
Clin Pharmacokinet 2002;41:187-95

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11929319
This review updates what is known about the pharmacokinetics of tirofiban in humans, especially in comparison with the monoclonal antibody against the IIb/IIIa receptor, abciximab.

Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial 
Kastrati A, et al. 
Lancet 2002;359:920-5.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11918909
In patients with acute myocardial infarction, a reperfusion strategy based on stenting with abciximab produced more myocardial salvage than the combination of fibrinolysis plus abciximab. Larger studies are needed to assess whether these effects translate into clinical benefit.

Comparison of efficacy and complication rates after percutaneous coronary interventions in patients with and without renal insufficiency treated with abciximab 
Frilling B, et al. 
Am J Cardiol 2002;89:450-2.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11835927

Pharmacodynamic profile of short-term readministration of abciximab in healthy subjects 
Freedman J, et al. 
Am Heart J 2002;143:87-94.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11773917

http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a119769&target=
A fraction of the bolus of abciximab restored pharmacologic (>80%) GP IIb/IIIa receptor blockade when readministered at various postinfusion time points. These observations suggest that in the setting where acute readministration of abciximab is required less than a full bolus dose of the agent is warranted.

Initial experience with the combination of reteplase and abciximab for thrombolytic therapy in peripheral arterial occlusive disease: a pilot study 
Drescher P, et al. 
J Vasc Interv Radiol 2002;13:37-43.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11788692

http://www.jvir.org/cgi/content/full/13/1/37

http://www.jvir.org/cgi/content/abstract/13/1/37
The combination of reteplase and abciximab in catheter-directed arterial thrombolysis is feasible and effective. This combination therapy pilot study suggests short thrombolysis times and minimal adverse effects in catheter-directed thrombolytic therapy for peripheral arterial occlusive disease.

Optimizing glycoprotein IIb/IIIa inhibition: lessons from recent randomized controlled trials 
Chew DP, et al. 
Intern Med J 2002;32:338-45.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12088354
Recent randomized clinical trials with intravenous glycoprotein IIb/IIIa inhibition have provided unanticipated results, thereby questioning their role as empirical medical management for acute coronary syndromes. The lack of benefit with abciximab observed in GUSTO IV is somewhat inconsistent with the benefits seen with this agent in coronary intervention, and the benefits of an early invasive approach incorporating tirofiban seen within TACTICS-TIMI 18. Additionally, a direct 'head-to-head' comparative study of abciximab and tirofiban within the setting of percutaneous coronary intervention demonstrates clinically relevant superiority with abciximab with respect to 30-day outcomes. in the setting of coronary instability and mechanical plaque disruption is more complex than initially perceived. Hence, although an abundance of evidence details the efficacy of these agents, their optimal clinical application remains somewhat challenging in light of these recent data. However, within the context of previous trial experience, the current evidence highlights several key aspects of glycoprotein IIb/IIIa inhibitor therapy that may be associated with improved patient outcomes. In particular, these trials indicate: (i) the importance of selecting high-risk patients in whom substantial clinical benefit is evident, (ii) the incorporation of these agents into an early invasive strategy, thereby matching the timing of vascular injury with maximal platelet inhibition and (iii) optimal dosing to achieve the high levels of platelet inhibition that appear to be required for efficacy with these agents.

Long-term mortality benefit with the combination of stents and abciximab for cardiogenic shock complicating acute myocardial infarction 
Chan AW, et al. 
Am J Cardiol 2002;89:132-6.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11792330
Treatment with the combination of stent and abciximab resulted in higher procedural Thrombolysis In Myocardial Infarction 3 flow rates and a long-term mortality benefit in patients with cardiogenic shock complicating acute myocardial infarction.

Editorial
Mechanical reperfusion therapy for acute myocardial infarction: Stent PAMI, ADMIRAL, CADILLAC and beyond 

Brodie BR, et al. 
Heart 2002;87:191-2.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11847146

http://heart.bmjjournals.com/cgi/content/full/87/3/191

Abciximab attenuates coronary microvascular endothelial dysfunction after coronary stenting 
Aymong ED, et al. 
Circulation 2002;105:2981-5.

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12081991

http://www.circulationaha.org/cgi/content/full/105/25/2981

http://www.circulationaha.org/cgi/content/abstract/105/25/2981
Abciximab preserves the Coronary blood flow (CBF) response to acetylcholine (Ach) after coronary stenting. The preservation of microvascular endothelial function may help explain the beneficial clinical effect of this agent in patients undergoing PCI.


Eptifibatide   Archive 2000-2001

Integrilin Trials - Free PowerPoint Slides
http://www.clinicaltrialresults.org/ua/integrilin/integrilin.htm
 

COR Therapeutics - INTEGRILIN®
http://www.corr.com

Treatment effects of eptifibatide in planned coronary stent implantation in patients with chronic kidney disease (ESPRIT Trial)
Reddan DN, et al.
Am J Cardiol 2003;91:17-21
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12505565 
Objective: explore the associations of creatinine clearance (CrCl) with outcomes in a trial of eptifibatide therapy in patients who underwent percutaneous coronary intervention (PCI). The treatment effect of eptifibatide is realized regardless of renal function and trends toward being greater in patients with mild renal impairment.

In-hospital costs of coronary stent implantation with and without eptifibatide (the ESPRIT Trial). Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin
Cohen DJ, et al.
Am J Cardiol 2002;89:61-4
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11779525 

Safety of concomitant therapy with eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: Results of the coronary revascularization using integrilin and single bolus enoxaparin study
D.L. Bhatt, B.I. Lee, P.J. Casterella, M. Pulsipher, M. Rogers, M. Cohen, V.E. Corrigan, T.J. Ryan, J.A. Breall, J.W. Moses, G.M. Eaton, M.A. Sklar, A.M. Lincoff
J Am Coll Cardiol 2003;41:20-25
Full text via ScienceDirect :
http://www.sciencedirect.com/science?_ob=GatewayURL&_origin=CONTENTS&_method=c
itationSearch&_piikey=S0735109702026311&_version=1&md5=14b26d6078f917c1c6ba19bf8a08935c
 
Compared with unfractionated heparin plus eptifibatide, the combination of enoxaparin plus eptifibatide is not associated with an excess of bleeding or vascular complications, including in those receiving closure devices. Despite no monitoring of anticoagulation activity with enoxaparin, there was no apparent increase in angiographic or clinical complications.

Same-day transradial outpatient stenting with a 6-hr course of glycoprotein IIb/IIIa receptor blockade: a feasibility study
Gilchrist IC, et al. 
Catheter Cardiovasc Interv 2002;56:10-3.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11979524
Outpatient stent placement with 6-hr infusion of GP IIb/IIIa inhibitor appears feasible and efficient in select patients. There may be challenges to meet with regard to patient education. Further studies with larger populations are needed to evaluate and optimize this approach

Gender differences in clinical outcome after coronary artery stenting with use of glycoprotein IIb/IIIa inhibitors 
Iakovou I, et al. 
Am J Cardiol 2002;89:976-9.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11950440

Pharmacodynamic profile of the direct thrombin antagonist bivalirudin given in combination with the glycoprotein IIb/IIIa antagonist eptifibatide 
Kleiman NS, et al. 
Am Heart J 2002;143:585-93.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11923794

http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a120297&target=
The findings of this study show the feasibility of combining the direct thrombin antagonist bivalirudin with a potent antagonist of platelet glycoprotein IIb-IIIa. Clinical trials are needed to assess the safety and efficacy of this combination.

Reversible thrombocytopenia associated with eptifibatide 
Yoder M, et al. 
Ann Pharmacother 2002;36:628-30.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11918511

http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=1060-0280&volume=36&issue=4&page=628
The temporal relationship to administration and the resolution of the adverse reaction on discontinuation of the drug support the likelihood that the severe, reversible thrombocytopenia was associated with eptifibatide.

A structural and dynamic investigation of the facilitating effect of glycoprotein IIb/IIIa inhibitors in dissolving platelet-rich clots 
Collet JP, et al. 
Circ Res 2002;90:428-34.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11884372

http://www.circresaha.org/cgi/content/full/90/4/428

http://www.circresaha.org/cgi/content/abstract/90/4/428
The results of this study demonstrate that fibrinolysis resistance of platelet-rich clots (PRCs) is related primarily to the heterogeneity in the clot structure between platelet-rich and platelet-poor areas. GP IIb/IIIa inhibitors facilitate the rate and the extent of fibrinolysis by improving rtPA binding velocity and, subsequently, the lysis rate in platelet-rich areas. These findings provide new insights on the synergistic potential of GP IIb/IIIa inhibitors and fibrinolytic agents.

Platelet aggregation inhibitors for use in peripheral vascular interventions: what can we learn from the experience in the coronary arteries? 
Shlansky-Goldberg R. 
J Vasc Interv Radiol 2002;13:229-46.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11875083

http://www.jvir.org/cgi/content/full/13/3/229

http://www.jvir.org/cgi/content/abstract/13/3/229
Because the majority of investigations have been performed in patients undergoing coronary interventions, knowledge of these data is necessary to attempt to translate the use of these antiplatelet drugs to peripheral vascular interventions. The goal of this article is to review the use of these agents in the percutaneous treatment of coronary artery disease and give insight to their potential utility in noncoronary interventions.

Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention
O'Shea JC, et al. 
Jama 2002;287:618-21.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11829701
Long-term outcomes of nonurgent coronary stent implantation appear to be improved through blockade of the platelet glycoprotein IIb/IIIa integrin with eptifibatide.
Although the mechanism behind these results remains unclear, similarities between eptifibatide's benefits and those of abciximab suggest a class effect. 
ESPRIT 1-year results published

Comment
Platelet glycoprotein IIb/IIIa inhibitor effect examined in 2 studies 
SoRelle R. 
Circulation 2002;105:E9067-8.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11826859

Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial 
Brener SJ, et al. 
J Am Coll Cardiol 2002;39:377-86.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11823073
In comparison with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h infusion and half-dose t-PA (Group II) is associated with improved quality and speed of reperfusion. The safety profile of this therapy is similar to that of other combination regimens.

Patients with acute coronary syndromes without persistent ST elevation undergoing percutaneous coronary intervention benefit most from early intervention with protection by a glycoprotein IIb/IIIa receptor blocker 
Ronner E, et al. 
Eur Heart J 2002;23:239-46.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11792139
Patients treated with a platelet glycoprotein IIb/IIIa receptor blocker, and early percutaneous coronary intervention (within 24 h) had the lowest event rate in this post hoc analysis. Thus 'watchful waiting' may not be the optimal strategy. Rather an early invasive strategy with percutaneous coronary intervention under protection of a platelet glycoprotein IIb/IIIa receptor blocker should be considered in selected patients. Randomized trials are warranted to verify this issue.

In-hospital costs of coronary stent implantation with and without eptifibatide (the ESPRIT Trial). Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin 
Cohen DJ, et al. 
Am J Cardiol 2002;89:61-4.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11779525


Tirofiban     Archive 1996-2001

Aggrastat Trials - Free PowerPoint Slides
http://www.clinicaltrialresults.org/ua/aggrastat/aggrastat_home.htm  

Aggrastat.com
www.aggrastat.com 
Website for Aggrastat ® (tirofiban HCI). 
Access: No registration required
Features: Educational material with Instructional video online. Treatment pathway and strategies. 

ESC 2002 Meeting Coverage

Tirofiban dose not high enough
The dose of tirofiban currently recommended does not give adequate platelet inhibition for optimal effects, a new study shows. 
European Society of Cardiology Congress 2002 [ Sep 06, 2002 ]

Comparison of degree of platelet inhibition by abciximab versus tirofiban in patients with unstable angina pectoris and non-Q-wave myocardial infarction undergoing percutaneous coronary intervention 
Herrmann HC, et al. 
Am J Cardiol 2002;89:1293-7.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12031731

Suboptimal early inhibition of platelets by treatment with tirofiban and implications for coronary interventions 
Kabbani SS, et al. 
Am J Cardiol 2002;89:647-50.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11867064

Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta3 integrin- mediated binding of smooth muscle cells to thrombospondin and prothrombin 
Scarborough RM. 
Circulation 2002;105:e46.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11839641

http://www.circulationaha.org/cgi/content/full/105/6/e46

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting: the TARGET Trial 
Stone GW, et al. 
Circulation 2002;105:2347-54.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12021219

http://www.circulationaha.org/cgi/content/full/105/20/2347

http://www.circulationaha.org/cgi/content/abstract/105/20/2347
In patients with ACS undergoing stent implantation, abciximab use compared with tirofiban results in greater suppression of periprocedural myonecrosis, although a survival benefit has not been demonstrated. Patients with stable coronary syndromes may have equivalent or better outcomes with tirofiban relative to abciximab, with fewer adverse hematologic and hemorrhagic events. These data raise important issues regarding the relative pharmacodynamic inhibition of platelet function required in varying clinical scenarios and have important implications for the cost-effective utilization of glycoprotein IIb/IIIa inhibitors.


Oral Gp IIb/IIIa blockers   Archive 2000-2001

Review 
Oral glycoprotein IIb/IIIa inhibitors increase mortality and myocardial infarction
ACP Journal Club. 2002 Nov-Dec;137:85.
http://www.acpjc.org/Content/137/3/issue/ACPJC-2002-137-3-085.htm  
Studies were identified by searching MEDLINE (1998 to 2001); reviewing abstracts from American College of Cardiology, European Society of Cardiology, and American Heart Association scientific sessions (1998 to 2001); and contacting investigators in the field.
The results of the meta-analysis by Newby and colleagues are consistent with other summaries. Oral GP IIb/IIIa inhibitors have not only failed to reduce late ischemic events, they are associated with a consistent excess in death and MI.

Review 
The failure of orally administered glycoprotein IIb/IIIa inhibitors to prevent recurrent cardiac events
Newby LK, Califf RM, White HD, et al. 
Am J Med. 2002 Jun 1;112:647-58. 
[PubMed ID: 12034415]


Miscellaneous  Archive 1987-2001

AHA 2002 Meeting Coverage

REPLACE-2 results: Will bivalirudin replace GP IIb/IIIa blockers in PCI?
UPDATED / with slides / Bivalirudin reduced major bleeding compared with heparin plus IIb/IIIa blockers in PCI patients in the REPLACE-2 study, but this benefit was offset somewhat by a nonsignificant increase in major events.
American Heart Association Scientific Sessions 2002. [ Nov 17, 2002 ]

REPLACE-2: Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events
The results indicate that bivalirudin is superior to heparin alone and is noninferior to heparin plus GP IIb/IIIa inhibitor therapy.

Italian
Studio REPLACE-2: valutazione randomizzata dell'interventistica
percutanea in associazione ad angiomax nella riduzione degli eventi clinici

Luis Gruberg, MD

An Update on Angiomax presented by The Medicines Co.  
Slide presentations include:

TCT 2002 Expert Presentations

Unfractionated Heparin, Low Molecular Weight Heparins, and Direct Thrombin Inhibitors M. Cohen  

TCT 2002 DEBATE: Heparinization (Without GP IIb/IIIa Inhibitors) in PCI - Does ACT Matter?

ACC 2002 Meeting Coverage

Current Data on Bivalirudin A. M. Lincoff

Summaries of important articles from major peer-reviewed journals

ASPECT-2 Study R. van Es   Lancet 2002; 360: 109-13  
Heparin + Alteplase Compared with Heparin Alone in Patients with Submassive PE S. Konstantinides   N Engl J Med 2002; 347:1143-1150  

Full text journal article May 2002
Bivalirudin With Planned or Provisional Abciximab Versus Low-Dose
Heparin and Abciximab During Percutaneous Coronary Revascularization

Bivalirudin with abciximab may be at least as safe and effective as low-dose heparin plus abciximab during PCI.

Full text journal article Ago 2002
Bivalirudin: A Direct Thrombin Inhibitor for Percutaneous Transluminal Coronary Angioplasty
Coronary artery disease affects more than 7 million Americans and accounts for more than 500,000 deaths/year in the United States.

Full text journal article Ago 2002
Stable and Optimal Anticoagulation is Achieved With a Single Dose of
Intravenous Enoxaparin in Patients Undergoing Percutaneous Coronary Intervention

Intravenous enoxaparin is safe and has a stable therapeutic anticoagulant effect within 4 hours of administration.

Full text journal article Jun 2002
Point-of-Care Versus Laboratory Monitoring of Patients Receiving Different Anticoagulant Therapies
This study compares point-of-care and standard hospital laboratory assays for monitoring anticoagulant regimens.

Full text journal article Oct 2002
Low Molecular Weight Heparin Therapy for Non-ST-Elevation Acute
Coronary Syndromes and During Percutaneous Coronary Intervention: An Expert Consensus

In patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI), new pharmacologic agents and improved revascularization techniques have reduced morbidity and mortality rates.

Full text journal article Aug 2002
Randomized Double-Blind Safety Study of Enoxaparin Versus Unfractionated Heparin in Patients With
Non-ST-Segment Elevation Acute Coronary Syndromes Treated With Tirofiban and Aspirin: The ACUTE II Study

Despite the use of numerous antithrombotic agents in patients with unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) syndromes, this patient population continues to demonstrate a risk of ischemic complications.

Efficacy and safety of minimal dose (</=1,000 Units) unfractionated heparin with abciximab in percutaneous coronary intervention
Denardo SJ, et al.
Am J Cardiol 2003;91:1-5
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12505562 
In the context of historical data, the efficacy and safety of PCI using either stent deployment or high-speed rotational atherectomy is maintained, if not improved, when performed using abciximab accompanied by only minimal doses of unfractionated heparin.

Comparison of Enoxaparin Versus Unfractionated Heparin in Patients With Unstable Angina Pectoris/Non-ST-Segment Elevation Acute Myocardial Infarction Having Subsequent Percutaneous Coronary Intervention
Fox KA, Antman EM, Cohen M, Bigonzi F, the ESSENCE/TIMI 11B Investigators
American Journal of Cardiology. 2002;90(5):477-482
http://www.medscape.com/viewarticle/443185_3 
The present ad hoc analysis, albeit despite the known limitations, presents data that are consistent with the evidence accumulated in previous smaller clinical trials and suggests that treatment with the LMWH enoxaparin is safe, effective, and well tolerated in UA/NSTEMI patients who undergo PCI. Furthermore, this drug is safe and effective in these patients regardless of whether they undergo PCI. As suggested by the authors, ongoing trials such as SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization & GlYcoprotein IIb/IIIa Inhibitors) will compare again these same drugs in high-risk patients likely to undergo PCI and provide a definite answer.

Mortality Benefit of Beta-Blockade After Successful Elective Percutaneous Coronary Intervention
Chan AW, Quinn MJ, Bhatt DL, et al.
Journal of The American College of Cardiology. 2002;40(4):669-675
http://www.medscape.com/viewarticle/441576_2
The present study shows that, in patients undergoing successful PCI, beta-blocker therapy should be considered and implemented concurrently, especially in high-risk patients who are not generally considered candidates for treatment, including patients with diabetes, reduced left ventricular function, chronic renal insufficiency, peripheral vascular disease, and multivessel coronary artery disease.

S-Nitrosoglutathione Reduces Asymptomatic Embolization After Carotid Angioplasty    
Zoltan Kaposzta et al
Circulation 2002;106 3057-3062
http://circ.ahajournals.org/cgi/content/abstract/106/24/3057?etoc
S-Nitrosoglutathione was highly effective in rapidly reducing the frequency of embolic signals after endovascular treatment for symptomatic high-grade carotid stenosis.

Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes
PARAGON Investigators
Circulation 2002;105:316-21.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11804986

http://www.circulationaha.org/cgi/content/full/105/3/316

http://www.circulationaha.org/cgi/content/abstract/105/3/316
Lamifiban showed no significant effects on clinical outcomes in patients with non-ST-elevation acute coronary syndromes, despite achievement of adequate plasma concentrations

Comparison of degree of platelet inhibition by abciximab versus tirofiban in patients with unstable angina pectoris and non-Q-wave myocardial infarction undergoing percutaneous coronary intervention
Herrmann HC, et al.
Am J Cardiol 2002;89:1293-7.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=12031731

Clinical Pharmacokinetics of Tirofiban, a Nonpeptide Glycoprotein IIb/IIIa Receptor Antagonist: Comparison with the Monoclonal Antibody Abciximab
Kondo K, et al.
Clin Pharmacokinet 2002;41:187-95
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11929319
This review updates what is known about the pharmacokinetics of tirofiban in humans, especially in comparison with the monoclonal antibody against the IIb/IIIa receptor, abciximab.