Thromb Haemost 2011; 106(04): 636-640
DOI: 10.1160/TH11-04-0257
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Suboptimal anticoagulation with pre-hospital heparin in ST-elevation myocardial infarction

Renicus S. Hermanides
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
,
Jan Paul Ottervanger
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
,
Jan-Henk E. Dambrink
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
,
Menko-Jan de Boer
2   Universitair Medisch Centrum Nijmegen, Dept of Cardiology, Nijmegen, The Netherlands
,
Jan C. A. Hoorntje
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
,
A. T. Marcel Gosselink
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
,
Harry Suryapranata
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
2   Universitair Medisch Centrum Nijmegen, Dept of Cardiology, Nijmegen, The Netherlands
,
Felix Zijlstra
3   Erasmus Medisch Centrum, Dept Cardiology, Rotterdam, The Netherlands
,
Arnoud W. J. van ’t Hof
1   Isala klinieken, Location Weezenlanden, Dept of Cardiology, Zwolle, The Netherlands
,
the Zwolle Myocardial Infarction Study Group › Author Affiliations
Further Information

Publication History

Received: 20 April 2011

Accepted after minor revision: 08 July 2011

Publication Date:
29 November 2017 (online)

Summary

This is a prospective, observational study performed in all consecutive ST-elevation myocardial infarction (STEMI) patients who had activated clotting time (ACT) measurement on arrival in the cathlab before coronary angiography. We studied the therapeutic effects of a pre-hospital fixed heparin bolus dose in consecutive patients with STEMI. A total of 1,533 patients received pre-hospital administration of aspirin, high dose clopidogrel (600 mg) and a fixed bolus dose of 5,000 IU unfractionated heparin (UFH), according to the national ambulance protocols. Some patients were also treated with glycoprotein IIb/IIIa inhibitors (GPI) in the ambulance. A therapeutic ACT range was defined according to the ESC guidelines as 200–250 seconds when patients had GPI pretreatment and 250–350 seconds when no GPI pretreatment. Of the 1,533 patients, 216 patients (14.1%) had an ACT within the therapeutic range, 82.3% of the patients had a too low ACT, whereas 3.5% of the patients had a too high ACT. After multivariable analysis, the only independent predictor of a too low ACT was increasing weight (odds ratio 1.02/kg, 95% confidence interval 1.01–1.03, p=0.001). Patients with a too low ACT had less often an open infarct related vessel (initial TIMI flow 2,3) as compared to patients with an ACT in range (36.5% vs. 45.9%, p=0.013). In only a minority of patients with STEMI, pre-hospital treatment with a fixed bolus dose UFH is within the therapeutic ACT range. Increased weight is an independent determinant of a too low ACT. We strongly recommend weight adjusted administration of UFH in the ambulance.

 
  • References

  • 1 Popma JJ, Weitz J, Bittl JA. et al. Antithrombotic therapy in patients undergoing coronary angioplasty. Chest 1998; 114: 728S.
  • 2 Wijns W, Kolh P, Danchin N. et al. The task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association of Cardio-Thoracic Surgery (EACTS). Guidelines on myocardial revascularization. Eur Heart J 2010; 31: 2501-2555.
  • 3 Cheng S, Morrow DA, Sloan S. et al. Predictors of initial nontherapeutic anticoagulation with unfractionated heparin in ST-segment elevation myocardial infarction. Circulation 2009; 119: 1195-1202.
  • 4 Alexander KP, Chen AY, Roe MT. et al CRUSADE Investigators. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. J Am Med Assoc 2005; 294: 3108-3116.
  • 5 Eikelboom JW, Metha SR, Anand SS. et al. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006; 114: 774-782.
  • 6 Manoukian SV, Feit F, Mehran R. et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY trial. J Am Coll Cardiol 2007; 49: 1362-1368.
  • 7 Montalescot G, Cohen M, Goldstein P. et al for the ATOLL investigators. Acute STEMI Treated with primary angioplasty and intravenous enoxaparin Or UFH to Lower ischemic and bleeding events at short- and Long-term follow-up trial. ESC, Stockholm, August 30 2010, Hotline session..
  • 8 Stone GW, WItzenbichler B, Guagliumi G. et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218-2230.
  • 9 Steg PG, Hamm C, Goldstein P. et al for the EUROMAX investigators. European Ambulance Acute Coronary Syndrome Angiox Trial: EUROMAX. http://clinical-trials.gov/ct2/show/NCT01087723
  • 10 Ellis SG, Tendera M, de Belder MA. et al for the FINESSE Investigators. Facilitated PCI in patients with ST-elevation myocardial infarction. New Engl J Med 2008; 358: 2205-2217.
  • 11 Chia S, Van Cott EM, Raffel OC. et al. Comparison of activated clotting times obtained using Hemochron and Medtronic analysers in patients receiving anti-thrombin therapy during cardiac catheterisation. Thromb Haemost 2009; 101: 413-603.
  • 12 Voyce SJ, Weiner BH, Becker RC. ACT monitoring: current applications in the angioplasty suite. Cardiology 1993; 10: 6-9.
  • 13 Rath B, Bennett DH. Monitoring the effect of heparin by measurement of activated clotting time during and after percutaneous transluminal coronary angioplasty. Br Heart J 1990; 63: 18-21.
  • 14 Avendano A, Ferguson JJ. Comparison of Hemochron and Hemotec activated coagulation time target values during percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1994; 23: 907-910.
  • 15 Doherty TM, Shavelle RM, French WJ. Reproducibility and variability of activated clotting time measurements in the cardiac catheterization laboratory. Catheter Cardiovasc Interv 2005; 65: 330-337.
  • 16 Himber J, Burcklen L, Steiner B. Effects of GP IIb/IIIa receptor antagonists on the activated clotting time of heparinized blood. Blood 2000; 95: 2189-2190.
  • 17 Moliterno DJ, Califf RM, Aguirre FV. et al. Effect of platelet glycoprotein IIb/IIIa integrin blockade on activated clotting time during percutaneous transluminal coronary angioplasty or directional atherectomy (the EPIC trial). Am J Cardiol 1995; 75: 559-562.
  • 18 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. J Am Coll Cardiol 2009; 54: 2205-2241.
  • 19 Chew DP, Bhatt DL, Lincoff AM. et al. Defining the optimal activated clotting time during percutaneous coronary intervention: Aggregate results from 6 randomized controlled trials. Circulation 2001; 103: 961-966.
  • 20 Blankenship JC, Balog C, Sapp SK. et al. Reduction in vascular access site bleeding in sequential abciximab coronary intervention trials. Catheter Cardiovasc Interv 2002; 57: 576-483.
  • 21 Popma JJ, Satler LF, Pichard AD. et al. Vascular complications after balloon and new device angioplasty. Circulation 1993; 88: 1569-1578.
  • 22 The EPILOG investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689-1696.
  • 23 Vainer J, Fleisch M, Gunnes P. et al. Low-dose heparin for routine coronary angioplasty and stenting. Am J Cardiol 1996; 78: 964-966.
  • 24 Lincoff AM, Tcheng JE, Califf RM. et al. PROLOG investigators. Standard versus low-dose weight adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 fab) during percutaneous coronary revascularization. Am J Cardiol 1997; 79: 286-291.
  • 25 Boccara A, Benamer H, Juliard JM. et al. A randomized trial of a fixed high dose vs a weight-adjusted low dose of intravenous heparin during coronary angioplasty. Eur Heart J 1997; 18: 631-635.
  • 26 Steg PG, Jolly SS, Metha SR. et al. Low-dose vs standard dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux. J Am Med Assoc 2010; 304: 1339-1349.
  • 27 Brener SJ, Moliterno DJ, Lincoff AM. et al. Relationship between activated clotting time and ischemic or hemorrhagic complications: analysis of 4 recent randomized clinical trials of percutaneous coronary intervention. Circulation 2004; 110: 994-998.
  • 28 Tolleson TR, O’Shea JC, Bittl JA. et al. Relationship between heparin anticoagulation and clinical outcomes in coronary stent intervention: observations from the ESPRIT trial. J Am Coll Cardiol 2003; 41: 386-393.
  • 29 Brieger D, Collet JP, Silvain J. et al. Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention. Catheter Cardiovasc Interv 2011; 77: 182-190.