0
August 13, 1997, Vol 278, No. 6 >
ARTICLE | August 13, 1997

Long-term Protection From Myocardial Ischemic Events in a Randomized Trial of Brief Integrin β3 Blockade With Percutaneous Coronary Intervention FREE

Eric J. Topol, MD; James J. Ferguson, MD; Harlan F. Weisman, MD; James E. Tcheng, MD; Stephen G. Ellis, MD; Neal S. Kleiman, MD; Russell J. Ivanhoe, MD; Ann L. Wang; David P. Miller, MS; Keaven M. Anderson, PhD; Robert M. Califf, MD
[+] Author Affiliations

A complete list of the Evaluation of Platelet llb/llla Inhibition for Prevention of Ischemic Complication (EPIC) Investigator Group can be found in Lancet. 1994;343: 881-886.

Reprints: Eric J. Topol, MD, Desk F25, Department of Cardiology, Cleveland Clinic Foundation, Cleveland, OH 44195 (e-mail: topole@cesmtp.ccf.org).


JAMA. 1997;278(6):479-484. doi:10.1001/jama.1997.03550060055036
Text Size: A A A
Published online
Article
References

Context.  —Avciximab,lonal antibody fragment against the platelet receptor αllbβ3 integrin, prevents platelet aggregation. A randomized, placebo-controlled study showed that abciximab improves outcomes for patients undergoing percutaneous coronary angioplasty at 30 days and at 6 months.

Objective.  —to determine whether abciximab improves outcomes 3 years after coronary angioplasty.

Design.  —Double-blind, placebo-controlled, randomized trial.

Setting.  —A total of 56 academic and community hospitals in the United States.

Patients.  —A total of 2099 high-risk patients undergoing coronary angioplasty were randomized. Sufficient time elapsed for 2.5 years of follow-up among 2001 patients and for 3 years of follow-up among 1599 patients.

Intervention.  —Abciximab bolus of 0.25 mg/kg followed by infusion at 10 μg/min for 12 hours; abciximab bolus of 0.25 mg/kg followed by placebo infusion; or placebo bolus followed by placebo infusion.

Main Outcomes Measures.  —The primary outcome was the composite of death, myocardial infarction, or coronary revascularization. Secondary outcomes were death, myocardial infarction, or coronary revascularization individually. Subgroups having refractory unstable angina or evolving myocardial infarction and having different elevations of creatine kinase during initial angioplasty were analyzed.

Results.  —At 3 years, composite end points occurred in 41.1% of those receiving abciximab bolus plus infusion; 47.4% of those receiving abciximab bolus only; and 47.2% of those receiving placebo only (for abciximab bolus plus infusion vs placebo, P=.009). Death occurred in 6.8%, 8.0%, and 8.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.20); myocardial infarction in 10.7%, 12.2%, and 13.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.08); and revascularization in 34.8%, 38.6%, and 40.1%, respectively (for abciximab bolus plus infusion vs placebo, P=.02). Among those with refractory unstable angina or evolving myocardial infarction, death occurred in 5.1%, 9.2%, and 12.7%, respectively (for abciximab bolus plus infusion vs placebo, P=.01). Death rates increased as periprocedural creatine kinase levels increased.

Conclusions.  —Adciximab bolus with infusion given at the time of coronary angioplasty improves outcomes as long as 3 years after the procedure.

REFERENCES

1 +
The BARI Investigators.  The Bypass Angioplasty Revascularization Investigation (BARI): five year mortality and morbidity in a randomized study comparing CABG and PTCA patients with multivessel coronary disease . N Engl J Med . 1996;;335:1217-1225.
2 +
Popma J, Califf RM, Topol EJ.  Clinical trials of restenosis after coronary angioplasty . Circulation . 1991;;84:1426-1436.
3 +
Topol EJ, Ellis SG, Cosgrove DM, et al.  Analysis of coronary angioplasty practice in the United States using a private insurance database . Circulation . 1993;;87:1489-1497.
4 +
Serruys PW, de Jaegere P, Kiemeneij F, et al.  A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease . N Engl J Med . 1994;;331:489-495.
5 +
Fischman DL, Leon MB, Baim DS, et al, for the Stent Restenosis Study Investigators.  A randomized comparison of stent placement and balloon angioplasty in the treatment of coronary artery disease . N Engl J Med . 1994;;331:496-501.
6 +
Topol EJ.  Caveats about elective coronary stenting . N Engl J Med . 1994;;331:539-541.
7 +
Weintraub WS, Boccuzzi SJ,Klein JL, et al.  Lack of effect of lovastatin on restenosis after coronary angioplasty . N Engl J Med . 1994;;331:1331-1337.
8 +
Serruys PW, Klein W, Tijssen JPG, et al.  Evaluation of ketanserin in the prevention of restenosis after percutaneous transluminal coronary angioplasty . Circulation . 1993;;88:1588-1601.
9 +
The Multicenter European Research Trial With Cilazapril After Angioplasty to Prevent Trans-luminal Coronary Obstruction and Restenosis (MERCATOR) Study Group.  Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous coronary angioplasty: results of the MERCATOR study: a multicenter, randomized, double-blind, placebocontrolled trial . Circulation . 1992;;86:100-110.
10 +
Hillegass WB, Ohman EM, Califf RM.  Restenosis: the clinical issues . In: Topol EJ, ed. Textbook of Interventional Cardiology . 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994;:415-435
11 +
Herrman JR, Hermans WRM, Vos J, Serruys PW.  Pharmacological approaches to the prevention of restenosis following angioplasty . Drugs . 1993;;46:259-262.
12 +
Serruys PW, Rutsch W, Heyndricks GR, et al.  Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade: a randomized, double-blind, placebo-controlled trial . Circulation . 1991;;84:1568-1580.
13 +
Leaf A, Jorgensen MB,Jacobs AK, et al.  Do fish oils prevent restenosis after coronary angioplasty? Circulation . 1994;;90:2248-2257.
14 +
Serruys PW, Herrman JPR, Simon R, et al.  A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty . N Engl J Med . 1995;;333:757-763.
15 +
Topol EJ, Califf RM, Weisman HF, et al, for the EPIC Investigators.  Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months . Lancet . 1994;;343:881-886.
16 +
The EPIC Investigators.  Prevention of ischemic complications in high-risk angioplasty by a chimeric monoclonal antibody c7E3 Fab fragment directed against the platelet glycoprotein IIb/IIIa receptor . N Engl J Med . 1994;;330:956-961.
17 +
Kaplan EL, Meier P.  Nonparametricestimation from incomplete observations . J Am Stat Assoc . 1958;;53:457-481.
18 +
Nelson W.  Graphical analysis of system repair data . J Qual Technol . 1987;;20:24-35.
19 +
Wong CB, Porter TR, Xie F, Deligonul U.  Segmental analysis of coronary arteries with equivalent plaque burden by intravascular ultrasound in patients with and without angiographically significant coronary artery disease . Am J Cardiol . 1995;; 76:598-603.
20 +
Abdelmeguid AE, Ellis SG, Sapp SK, Whitlow PL, Topol EJ.  Defining the appropriate threshold of creatine kinase elevation after percutaneous coronary interventions . Am Heart J . 1996;;131:1097-1105.
21 +
Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG.  Significance of mild transient release of creatine kinase MB fraction after percutaneous interventions . Circulation . 1996;;94:1528-1536.
22 +
Redwood SR, Popma JJ, Kent KM, et al.  'Minor' CPK-MB elevations are associated with increased late mortality following ablative new-device angioplasty in native coronary arteries . Circulation . 1995;; 92( (suppl 1) ):1544. Abstract.
23 +
Tardiff BE, Califf RM, Tcheng JE, et al, for the IMPACT II Investigators.  Post-intervention cardiac enzyme elevations: prognostic significance in IMPACT TI . J Am Coll Cardiol . 1996;;27( (suppl A) ): A-83A. Abstract.
24 +
Abdelmeguid AE, Whitlow PL, Sapp SK, Ellis SG, Topol EJ.  Long-term outcome of transient, uncomplicated, in-laboratory coronary artery closure . Circulation . 1995;;91:2733-2741.
25 +
Kong TQ, Davidson CJ, Meyers SN, Tauke JT, Parker MA, Bonow RO.  Prognostic implication of creatine kinase elevation following elective coronary artery interventions .JAMA . 1997;;277:461-466.
26 +
Coller BS.  A new murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet GP IIb/IIIa complex .J Clin Invesst . 1985;;76:101-108.
27 +
Lefkovits J, Plow EF, Topol EJ.  Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine . N Engl J Med . 1995;;332:1553-1559.
28 +
Jones JI, Prevette T, Gockerman A, Clemmons DR.  Ligand occupancy of the αvβ3 integrin is necessary for smooth muscle cells to migrate in response to insulin-like growth factor I . Proc Natl Acad Sci U S A . 1996;;93:2482-2487.
29 +
Choi ET, Engel L, Callow AD, et al.  Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist Gpen GRGDSPCA . J Vasc Surg . 1994;;19:125-134.
30 +
LeBreton H, Rabbani R, Plow E, et al.  The role of integrins αIIbβ3 (glycoprotein IIb/IIIa) and αvβ3 (the vitronectin receptor) in a guinea pig model of restenosis . Circulation . 1996;;94( (suppl) ):I-517. Abstract.
31 +
Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA.  Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin αvβ3 duringangiogenesis . J Clin Invest . 1996;;98:426-433.
32 +
Speir E, Modali R, Huang ES, et al.  Potential role of human cytomegalovirus and p53 interaction in coronary restenosis . Science . 1994;;265:391-394.
33 +
Zhou YF, Leon MB, Waclawiw MA, et al.  Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy . N Engl J Med . 1996;;335:624-630.
34 +
Reverter JC, Beguin S, Kessels H, Kumar R, Hemker HC, Coller BS.  Inhibition of platelet-mediated, tissue factor—induced thrombin generation by the mouse/human chimeric 7E3 antibody: potential implications for the effect of c7E3 Fab treatment on acute thrombosis and 'clinical restenosis.' J Clin Invest . 1996;;98:863-874.
35 +
The GUSTO II Angioplasty Substudy Investigators.  A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator and recombinant hirudin with heparin foracute myocardial infarction . N Engl J Med . 1997;;336:1621-1628.
36 +
Antiplatelet Trialists' Collaboration.  Collaborative overview of randomized trials of antiplatelet therapy, 1: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients . BMJ . 1994;;308:81-106.
37 +
Latini R, Maggioni AP, Flather M, Sleight P, Tognoni G.  ACE inhibitor use in patients with myocardial infarction: summary of evidence from clinical trials . Circulation . 1995;;92:3132-3137.
38 +
Scandinavian Simvastatin Survival Study Group.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) . Lancet . 1994;;344:1383-1389.
39 +
Teo KK, Yusuf S, Furberg CD.  Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction: an overview of results from randomized controlled trials . JAMA . 1988;;260:1910-1916.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
The BARI Investigators.  The Bypass Angioplasty Revascularization Investigation (BARI): five year mortality and morbidity in a randomized study comparing CABG and PTCA patients with multivessel coronary disease . N Engl J Med . 1996;;335:1217-1225.
2 +
Popma J, Califf RM, Topol EJ.  Clinical trials of restenosis after coronary angioplasty . Circulation . 1991;;84:1426-1436.
3 +
Topol EJ, Ellis SG, Cosgrove DM, et al.  Analysis of coronary angioplasty practice in the United States using a private insurance database . Circulation . 1993;;87:1489-1497.
4 +
Serruys PW, de Jaegere P, Kiemeneij F, et al.  A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease . N Engl J Med . 1994;;331:489-495.
5 +
Fischman DL, Leon MB, Baim DS, et al, for the Stent Restenosis Study Investigators.  A randomized comparison of stent placement and balloon angioplasty in the treatment of coronary artery disease . N Engl J Med . 1994;;331:496-501.
6 +
Topol EJ.  Caveats about elective coronary stenting . N Engl J Med . 1994;;331:539-541.
7 +
Weintraub WS, Boccuzzi SJ,Klein JL, et al.  Lack of effect of lovastatin on restenosis after coronary angioplasty . N Engl J Med . 1994;;331:1331-1337.
8 +
Serruys PW, Klein W, Tijssen JPG, et al.  Evaluation of ketanserin in the prevention of restenosis after percutaneous transluminal coronary angioplasty . Circulation . 1993;;88:1588-1601.
9 +
The Multicenter European Research Trial With Cilazapril After Angioplasty to Prevent Trans-luminal Coronary Obstruction and Restenosis (MERCATOR) Study Group.  Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous coronary angioplasty: results of the MERCATOR study: a multicenter, randomized, double-blind, placebocontrolled trial . Circulation . 1992;;86:100-110.
10 +
Hillegass WB, Ohman EM, Califf RM.  Restenosis: the clinical issues . In: Topol EJ, ed. Textbook of Interventional Cardiology . 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994;:415-435
11 +
Herrman JR, Hermans WRM, Vos J, Serruys PW.  Pharmacological approaches to the prevention of restenosis following angioplasty . Drugs . 1993;;46:259-262.
12 +
Serruys PW, Rutsch W, Heyndricks GR, et al.  Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade: a randomized, double-blind, placebo-controlled trial . Circulation . 1991;;84:1568-1580.
13 +
Leaf A, Jorgensen MB,Jacobs AK, et al.  Do fish oils prevent restenosis after coronary angioplasty? Circulation . 1994;;90:2248-2257.
14 +
Serruys PW, Herrman JPR, Simon R, et al.  A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty . N Engl J Med . 1995;;333:757-763.
15 +
Topol EJ, Califf RM, Weisman HF, et al, for the EPIC Investigators.  Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months . Lancet . 1994;;343:881-886.
16 +
The EPIC Investigators.  Prevention of ischemic complications in high-risk angioplasty by a chimeric monoclonal antibody c7E3 Fab fragment directed against the platelet glycoprotein IIb/IIIa receptor . N Engl J Med . 1994;;330:956-961.
17 +
Kaplan EL, Meier P.  Nonparametricestimation from incomplete observations . J Am Stat Assoc . 1958;;53:457-481.
18 +
Nelson W.  Graphical analysis of system repair data . J Qual Technol . 1987;;20:24-35.
19 +
Wong CB, Porter TR, Xie F, Deligonul U.  Segmental analysis of coronary arteries with equivalent plaque burden by intravascular ultrasound in patients with and without angiographically significant coronary artery disease . Am J Cardiol . 1995;; 76:598-603.
20 +
Abdelmeguid AE, Ellis SG, Sapp SK, Whitlow PL, Topol EJ.  Defining the appropriate threshold of creatine kinase elevation after percutaneous coronary interventions . Am Heart J . 1996;;131:1097-1105.
21 +
Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG.  Significance of mild transient release of creatine kinase MB fraction after percutaneous interventions . Circulation . 1996;;94:1528-1536.
22 +
Redwood SR, Popma JJ, Kent KM, et al.  'Minor' CPK-MB elevations are associated with increased late mortality following ablative new-device angioplasty in native coronary arteries . Circulation . 1995;; 92( (suppl 1) ):1544. Abstract.
23 +
Tardiff BE, Califf RM, Tcheng JE, et al, for the IMPACT II Investigators.  Post-intervention cardiac enzyme elevations: prognostic significance in IMPACT TI . J Am Coll Cardiol . 1996;;27( (suppl A) ): A-83A. Abstract.
24 +
Abdelmeguid AE, Whitlow PL, Sapp SK, Ellis SG, Topol EJ.  Long-term outcome of transient, uncomplicated, in-laboratory coronary artery closure . Circulation . 1995;;91:2733-2741.
25 +
Kong TQ, Davidson CJ, Meyers SN, Tauke JT, Parker MA, Bonow RO.  Prognostic implication of creatine kinase elevation following elective coronary artery interventions .JAMA . 1997;;277:461-466.
26 +
Coller BS.  A new murine monoclonal antibody reports an activation-dependent change in the conformation and/or microenvironment of the platelet GP IIb/IIIa complex .J Clin Invesst . 1985;;76:101-108.
27 +
Lefkovits J, Plow EF, Topol EJ.  Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine . N Engl J Med . 1995;;332:1553-1559.
28 +
Jones JI, Prevette T, Gockerman A, Clemmons DR.  Ligand occupancy of the αvβ3 integrin is necessary for smooth muscle cells to migrate in response to insulin-like growth factor I . Proc Natl Acad Sci U S A . 1996;;93:2482-2487.
29 +
Choi ET, Engel L, Callow AD, et al.  Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist Gpen GRGDSPCA . J Vasc Surg . 1994;;19:125-134.
30 +
LeBreton H, Rabbani R, Plow E, et al.  The role of integrins αIIbβ3 (glycoprotein IIb/IIIa) and αvβ3 (the vitronectin receptor) in a guinea pig model of restenosis . Circulation . 1996;;94( (suppl) ):I-517. Abstract.
31 +
Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA.  Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin αvβ3 duringangiogenesis . J Clin Invest . 1996;;98:426-433.
32 +
Speir E, Modali R, Huang ES, et al.  Potential role of human cytomegalovirus and p53 interaction in coronary restenosis . Science . 1994;;265:391-394.
33 +
Zhou YF, Leon MB, Waclawiw MA, et al.  Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy . N Engl J Med . 1996;;335:624-630.
34 +
Reverter JC, Beguin S, Kessels H, Kumar R, Hemker HC, Coller BS.  Inhibition of platelet-mediated, tissue factor—induced thrombin generation by the mouse/human chimeric 7E3 antibody: potential implications for the effect of c7E3 Fab treatment on acute thrombosis and 'clinical restenosis.' J Clin Invest . 1996;;98:863-874.
35 +
The GUSTO II Angioplasty Substudy Investigators.  A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator and recombinant hirudin with heparin foracute myocardial infarction . N Engl J Med . 1997;;336:1621-1628.
36 +
Antiplatelet Trialists' Collaboration.  Collaborative overview of randomized trials of antiplatelet therapy, 1: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients . BMJ . 1994;;308:81-106.
37 +
Latini R, Maggioni AP, Flather M, Sleight P, Tognoni G.  ACE inhibitor use in patients with myocardial infarction: summary of evidence from clinical trials . Circulation . 1995;;92:3132-3137.
38 +
Scandinavian Simvastatin Survival Study Group.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) . Lancet . 1994;;344:1383-1389.
39 +
Teo KK, Yusuf S, Furberg CD.  Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction: an overview of results from randomized controlled trials . JAMA . 1988;;260:1910-1916.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Response

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems