Journal Mobile Options
Table of Contents
Vol. 108, No. 4, 2007
Issue release date: November 2007
Cardiology 2007;108:265–272

Efficacy and Safety of Clopidogrel 600 mg Administered Pre-Hospitally to Improve Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction (CIPAMI): Study Rationale and Design

Zeymer U. · Arntz H.-R. · Darius H. · Huber K. · Senges J.
aHerzzentrum Ludwigshafen und Institut für Herzinfarktforschung, Ludwigshafen, bMedizinische Klinik II, Kardiologie und Pulmonologie, Charité Campus Benjamin Franklin, and cVivantes Klinikum Berlin-Neukölln, Klinik für Innere Medizin, Kardiologie, Berlin, Germany; dWilhelminenspital, III. Medical Department, Internal Medicine, Vienna, Austria

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Clopidogrel, in combination with acetylsalicylic acid, has become a mainstay of the pharmacological therapy for patients with acute coronary syndromes, especially in those undergoing percutaneous coronary interventions (PCI). While a series of studies has shown that pre-treatment with a loading dose of clopidogrel 300 or 600 mg prior to PCI is effective in reducing cardiovascular complications, the optimal dose and timing in various patient groups is still unclear. The primary objective of the present randomized, open-label Clopidogrel to Improve Primary percutaneous coronary Intervention in Acute Myocardial Infarction (CIPAMI) study is to evaluate the efficacy and the safety of a 600 mg loading dose of clopidogrel in addition to standard acetylsalicylic acid/heparin treatment in the pre-hospital setting in 654 patients with acute ST elevation myocardial infarction scheduled for primary PCI. The primary efficacy endpoint is the TIMI 2/3 patency of the infarct-related artery immediately prior to PCI. The rationale, design and methods of this study are described.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Simes RJ, Topol EJ, Holmes DR Jr, White HD, Rutsch WR, Vahanian A, Simoons ML, Morris D, Betriu A, Califf RM, et al: Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation 1995;91:1923–1928.
  2. Anderson JL, Karagounis LA, Califf RM: Metaanalysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction. Am J Cardiol 1996;78:1–8.
  3. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, Jacobs AK, Kern MJ, King SB 3rd, Morrison DA, O’Neill W W, Schaff HV, Whitlow PL, et al: ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention-summary article: 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). Catheter Cardiovasc Interv 2006;67:87–112.
  4. Silber S, Albertsson P, Aviles FF, Camici PG, Colombo A, Hamm C, Jorgensen E, Marco J, Nordrehaug JE, Ruzyllo W, et al: Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 2005;26:804–847.
  5. Weaver WD, Simes RJ, Betriu A, Grines CL, Zijlstra F, Garcia E, Grinfeld L, Gibbons RJ, Ribeiro EE, DeWood MA, et al: Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997;278:2093–2098.
  6. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. N Engl J Med 1997;336:1621–1628.
  7. Claeys MJ, Bosmans J, Veenstra L, Jorens P, De Raedt H, Vrints CJ: Determinants and prognostic implications of persistent ST-segment elevation after primary angioplasty for acute myocardial infarction: importance of microvascular reperfusion injury on clinical outcome. Circulation 1999;99:1972–1977.
  8. Santoro GM, Antoniucci D, Valenti R, Bolognese L, Buonamici P, Trapani M, Boddi V, Fazzini PF: Rapid reduction of ST-segment elevation after successful direct angioplasty in acute myocardial infarction. Am J Cardiol 1997;80:685–689.
  9. Neumann FJ, Blasini R, Schmitt C, Alt E, Dirschinger J, Gawaz M, Kastrati A, Schomig A: Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998;98:2695–2701.
  10. Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P, Boulenc JM, Morice MC, Maillard L, Pansieri M, et al: Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001;344:1895–1903.
  11. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group: Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Circulation 2000;101:2788–2794.

    External Resources

  12. de Lemos JA, Antman EM, Gibson CM, McCabe CH, Giugliano RP, Murphy SA, Coulter SA, Anderson K, Scherer J, Frey MJ, et al: Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial. Circulation 2000;101:239–243.
  13. Gyongyosi M, Domanovits H, Benzer W, Haugk M, Heinisch B, Sodeck G, Hodl R, Gaul G, Bonner G, Wojta J, et al: Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion – results of the Austrian multi-centre randomized ReoPro-BRIDGING Study. Eur Heart J 2004;25:2125–2133.
  14. Lee DP, Herity NA, Hiatt BL, Fearon WF, Rezaee M, Carter AJ, Huston M, Schreiber D, DiBattiste PM, Yeung AC: Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial. Circulation 2003;107:1497–1501.
  15. Zeymer U, Zahn R, Schiele R, Jansen W, Girth E, Gitt A, Seidl K, Schroder R, Schneider S, Senges J: Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial. Eur Heart J 2005;26:1971–1977.
  16. Zorman S, Zorman D, Noc M: Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty. Am J Cardiol 2002;90:533–536.
  17. van’t Hof AW, Ernst N, de Boer MJ, de Winter R, Boersma E, Bunt T, Petronio S, Marcel Gosselink AT, Jap W, Hollak F, et al: Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. Eur Heart J 2004;25:837–846.
  18. Brodie BR, Stuckey TD, Hansen C, Muncy D: Benefit of coronary reperfusion before intervention on outcomes after primary angioplasty for acute myocardial infarction. Am J Cardiol 2000;85:13–18.
  19. Stone GW, Cox D, Garcia E, Brodie BR, Morice MC, Griffin J, Mattos L, Lansky AJ, O’Neill WW, Grines CL: Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials. Circulation 2001;104:636–641.
  20. Montalescot G, Borentain M, Payot L, Collet JP, Thomas D: Early vs. late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis. JAMA 2004;292:362–366.
  21. Goedicke J, Flather M, Arntz H-R, Gabriel H, Grip L, Huber K, Noc M, Montalescot G: Upstream administration of abciximab prior to primary angioplasty improves epicardial patency and myocardial tissue perfusion: Results from a meta-analysis of 602 cases [abstract]. J Am Coll Cardiol 2005;45(suppl A):250A.
  22. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction. Lancet 1988;2:349–360.
  23. Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH; for the CLASSICS Investigators: Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000;102:624–629.
  24. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502.
  25. Budaj A, Yusuf S, Mehta SR, Fox KA, Tognoni G, Zhao F, Chrolavicius S, Hunt D, Keltai M, Franzosi MG: Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups. Circulation 2002;106:1622–1626.
  26. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, 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.
  27. Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411–2420.
  28. Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, et al: Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179–1189.
  29. Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E, 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.
  30. Fitzgerald DJ, Roy L, Catella F, FitzGerald GA: Platelet activation in unstable coronary disease. N Engl J Med 1986;315:983–989.
  31. Gawaz M, Neumann FJ, Ott I, Schiessler A, Schomig A: Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996;93:229–237.
  32. Gurbel PA, Cummings CC, Bell CR, Alford AB, Meister AF, Serebruany VL: Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial. Am Heart J 2003;145:239–247.
  33. Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS: Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1607–1621.
  34. Muller I, Seyfarth M, Rudiger S, Wolf B, Pogatsa-Murray G, Schomig A, Gawaz M: Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001;85:92–93.
  35. Steinhubl SR, Talley JD, Braden GA, Tcheng JE, Casterella PJ, Moliterno DJ, Navetta FI, Berger PB, Popma JJ, Dangas G, et al: Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation 2001;103:2572–2578.
  36. Kastrati A, Mehilli J, Schuhlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, et al: A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004;350:232–238.
  37. Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G: Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation 2005;111:2099–2106.
  38. Montalescot G, Verheugt F, Sabatine MS, Soulst L, Lambert Y, Lapostolle F, Adgey J, Cannon CP: Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation myocardial infarction. The prehospital CLARITY-TIMI 28 substudy [abstract 2891]. Circulation 2005;112(suppl 2):567.
  39. Zeymer U: PREMIR (Prähospitales Myokardinfarktregister). Hotline Session III. Presentation at 71. Jahrestagung der Deutschen Gesellschaft für Kardiologie. Mannheim, Germany, 2 April 2005.
  40. Zeymer U, Zahn R, Hochadel M, Bonzel T, Weber M, Gottwik M, Tebbe U, Senges J: Indications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Results of the quality control registry of the Arbeitsgemeinschaft Leitender kardiologischer Krankenhausärzte (ALKK). Z Kardiol 2005;94:392–398.
  41. American Heart Association: Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care: Part 4: Adult basic life support. Circulation 2005;112(suppl IV):19–34.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50