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Thromb Haemost 2014; 112(03): 606-613
DOI: 10.1160/TH13-11-0951
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Early ambulance initiation versus in-hospital initiation of high dose clopidogrel in ST-segment elevation myocardial infarction

Sonja Postma
1   Diagram, Zwolle, The Netherlands
,
Jan-Henk E. Dambrink
2   Isala hospital, Zwolle, The Netherlands
,
Jan Paul Ottervanger
2   Isala hospital, Zwolle, The Netherlands
,
Marcel A.T. Gosselink
2   Isala hospital, Zwolle, The Netherlands
,
Petra C. Koopmans
1   Diagram, Zwolle, The Netherlands
,
Jurrien M. ten Berg
3   St Antonius Hospital Nieuwegein, The Netherlands
,
Harry Suryapranata
1   Diagram, Zwolle, The Netherlands
4   UMC St Radboud Nijmegen, The Netherlands
,
Arnoud W. J. van ’t Hof
2   Isala hospital, Zwolle, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 19 November 2013

Accepted after major revision: 27 March 2014

Publication Date:
20 November 2017 (online)

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Summary

Pre-hospital infarct diagnosis gives the opportunity to start anti-platelet and anti-thrombotic agents before arrival at the PCI centre. However, more evidence is necessary to demonstrate whether high dose (HD) clopidogrel (600 mg) administered in the ambulance is associated with improved initial patency of the infarct related vessel (IRV) and/or clinical outcome compared to in-hospital initiation of HD clopidogrel. From 2001 until 2009 all consecutive ST-Segment Elevation Myocardial Infarction (STEMI) patients who underwent pre-hospital diagnosis and therapy in the ambulance were prospectively included in our single-centre cohort study. We compared initial patency of the IRV and clinical outcome in patients treated from 2001 until June 2006 (in-hospital HD clopidogrel) with patients treated from July 2006 until 2009 (ambulance HD clopidogrel). A total of 2,475 patients with STEMI were registered; of these 1,110 (44.8%) received in-hospital HD clopidogrel and 1,365 (55.2%) received ambulance HD clopidogrel. Ambulance HD clopidogrel was not independently associated with initial patency (TIMI-2/3-flow pre-PCI (odds ratio: 1.18, 95% confidence interval [CI] 0.96–1.44); however, it was associated with fewer recurrent myocardial infarctions at 30 days (hazard ratio [HR]: 0.45, 95% CI 0.22–0.93) and at one year (HR: 0.45, 95% CI 0.25–0.80). No difference in TIMI 2/3 flow post-PCI, major bleeding, mortality, MACE – and the combination of mortality and recurrent myocardial infarction at 30-days and at one year was present between the two groups. In conclusion, early in-ambulance as compared to in-hospital initiation of HD clopidogrel in STEMI patients did not improve initial patency of the IRV or clinical outcome, except for a reduction of recurrent myocardial infarction. Therefore, early administration of HD clopidogrel seems to have net clinical benefit for these patients .

Keywords

Clopidogrel - initial patency - pre-hospital - STEMI
 

  • References

  • 1 Kushner FG, Hand M, Smith Jr SC. et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/ AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009; 120: 2271-2306.
    CrossrefPubMedGoogle Scholar
  • 2 Steg G, James SK, Atar D. et al. The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619.
    CrossrefPubMedGoogle Scholar
  • 3 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.
    PubMedGoogle Scholar
  • 4 Zijlstra F, Ernst N, de Boer MJ. et al. Influence of prehospital administration of aspirin and heparin on initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction. J Am Coll Cardiol 2002; 39: 1733-1737.
    CrossrefPubMedGoogle Scholar
  • 5 Verheugt FW, Liem AL, Zijlstra F. et al. High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: results of the Heparin in Early Patency (HEAP) pilot study. J Am Coll Cardiol 1998; 31: 289-293.
    PubMedGoogle Scholar
  • 6 Liem AL, Zijlstra F, Ottervanger JP. et al. High dose heparin as pre-treatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial. J Am Coll Cardiol 2000; 35: 600-604.
    CrossrefPubMedGoogle Scholar
  • 7 van ’t Hof AWJ, Liem A, de Boer MJ. et al. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Lancet 1997; 350: 615-619.
    CrossrefPubMedGoogle Scholar
  • 8 van ’t Hof AWJ, Ernst N, de Boer MJ. et al. Facilitation of primary coronary angioplasty by early start of glycoprotein 2b.3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. Eur Heart J 2004; 25: 837-846.
    CrossrefPubMedGoogle Scholar
  • 9 van ’t Hof AWJ, ten Berg JM, Heestermans AACM. et al. Ongoing Tirofiban In Myocardial Infarction Evaluation (ON-TIME) 2 Study group. Pre-hospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (ON-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet 2008; 372: 537-546.
    CrossrefPubMedGoogle Scholar
  • 10 van ’t Hof AWJ, Rasoul S, Wetering H. et al Feasibility and benefit of prehospital diagnosis, triage, and therapy by paramedics only in patients who are candidates for primary angioplasty for acute myocardial infarction. Am Heart J 2006; 151 1255 e1-5.
    PubMedGoogle Scholar
  • 11 TIMI study group. The Thrombolysis In Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med 1985; 312: 932-936.
    PubMedGoogle Scholar
  • 12 Rao AK, Pratt C, Berke A. et al. Thrombolysis in Myocardial infarction (TIMI) Trial - phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11: 1-11.
    CrossrefPubMedGoogle Scholar
  • 13 Muller I, Seyfarth M, Rudiger S. et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001; 85: 92-93.
    CrossrefPubMedGoogle Scholar
  • 14 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. J Am Coll Cardiol 2006; 48: 931-938.
    CrossrefPubMedGoogle Scholar
  • 15 Hermanides RS, Heestermans AACM, ten Berg JM. et al. High-dose tirofiban pretreatment reduces the need for bail-out study medication in patients with ST-segment elevation myocardial infarction: results of a subgroup analysis of the On-TIME 2 trial. Heart 2011; 97: 106-111.
    CrossrefPubMedGoogle Scholar
  • 16 Smit JJ, van Werkum JW, ten Berg JM. et al. Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy. Heart 2010; 96: 1815-1820.
    CrossrefPubMedGoogle Scholar
  • 17 Heestermans AACM, van Werkum JW, Taubert D. et al. Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction. Thromb Res 2008; 122: 776-781.
    CrossrefPubMedGoogle Scholar
  • 18 Fefer P, Hod H, Hammerman H. et al. Usefulness of pre-treatment with high-dose clopidogrel in patients undergoing primary angioplasty for ST-elevation myocardial infarction. Am J Cardiol 2009; 104: 514-518.
    CrossrefPubMedGoogle Scholar
  • 19 Larson DM, Duval S, Sharkey SS. et al. Clopidogrel pre-treatment in ST-elevation myocardial infarction patients transferred for percutaneous coronary intervention. Am Heart J 2010; 160: 202-207.
    CrossrefPubMedGoogle Scholar
  • 20 Dörler J, Edlinger M, Alber HF. et al. Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarct. Eur Heart J 2011; 32: 2954-2961.
    CrossrefPubMedGoogle Scholar
  • 21 Zeymer U, Arntz HR, Mark B. et al. Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial. Clin Res Cardiol 2012; 101: 305-312.
    CrossrefPubMedGoogle Scholar
  • 22 Koul S, Smith JG, Schersten F. et al. Effect of upstream clopidogrel treatment in patients with ST-elevation myocardial infarction undergoing primary coronary intervention. Eur Heart J 2011; 32: 2989-2997.
    CrossrefPubMedGoogle Scholar
  • 23 Montalescot G, Bolognese L, Dudek D. et al. For the ACCOAST investigators. Pretreatment with Prasugrel in Non-ST-Segment Elevation Acute Coronary Syndromes. N Eng J Med 2013; 369: 999-1010.
    CrossrefPubMedGoogle Scholar
  • 24 Ducci K, Grotti S, Falsini G. et al. Comparison of pre-hospital 600 mg or 900 mg vs. peri-interventional 300 mg clopidogrel in patients with ST-elevation myocardial infarction undergoing primary coronary angioplasty. The Load&Go randomized trial. Int J of Cardiol 2013; 168: 4814-4816.
    PubMedGoogle Scholar
  • 25 Vlaar PJ, Svilaas T, Damman K. et al. Impact of pretreatment with clopidogrel on initial patency and outcome in patients treated with primary percutaneous coronary intervention for ST-segment elevated myocardial infarction. A systematic review. Circulation 2008; 118: 1828-1836.
    CrossrefPubMedGoogle Scholar
  • 26 Lev EI, Kornowski R, Vaknin-Assa H. et al. Effect of clopidogrel pretreatment on angiographic and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. Am J Cardiol 2008; 101: 435-439.
    CrossrefPubMedGoogle Scholar
  • 27 Heestermans AACM, de Boer MJ, van Werkum JW. et al. Higher efficacy of pre-hospital tirofiban with longer pre-treatment time to primary PCI: protection for the negative impact of time delay. EuroIntervention 2011; 07: 442-4228.
    CrossrefPubMedGoogle Scholar
  • 28 Heestermans AACM, van ’t Hof AWJ, ten Berg JM. et al. The golden hour of prehospital reperfusion with triple antiplatelet therapy: a sub-analysis from the Ongoing Tirofiban in Myocardial Evaluation 2 (On-TIME 2) trial early initiation of triple antiplatelet therapy. Am Heart J 2010; 160: 1079-1084.
    CrossrefPubMedGoogle Scholar
  • 29 Steg PG, Bhatt DL, Hamm CW. et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013; 382: 1981-1992.
    CrossrefPubMedGoogle Scholar