Thromb Haemost 2013; 109(05): 961-970
DOI: 10.1160/TH12-10-0726
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Prognostic value of post-procedural aPTT in patients with ST-elevation myocardial infarction treated with primary PCI

Wouter J. Kikkert
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Sophie H. van Nes
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Krystien V. V. Lieve
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
George D. Dangas
2   Cardiovascular Research Foundation, New York, New York, USA
3   Mount Sinai Medical Center, New York, New York, USA
,
Jan van Straalen
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Marije M. Vis
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Jan Baan Jr
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Karel T. Koch
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Robbert J. de Winter
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Jan J. Piek
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Jan G. P. Tijssen
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Jose P. Henriques
1   Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 03. Oktober 2012

Accepted after major revision: 25. Januar 2013

Publikationsdatum:
22. November 2017 (online)

Summary

Unfractionated heparin is the most commonly used anticoagulant in ST-elevation myocardial infarction (STEMI) and its effect can be monitored with activated partial thromboplastin time (aPTT). However, the optimal aPTT range during heparin therapy after primary percutaneous coronary intervention (PCI) is yet to be defined. A mean aPTT was calculated of all aPTT measurements in the first 24 hours after pPCI in a total of 1,876 STEMI patients. Mean aPTT measurements were stratified into four categories; < 1.5 times the upper limit of normal (ULN), 1.5 – 2.0 times ULN (the therapeutic group), 2.01 – 3.99 times ULN, and ≥ 4 times ULN. Compared to patients with a therapeutic aPTT, patients with aPTTs < 1.5 times ULN had no increase in recurrent ischaemic events and had similar rates of bleeding complications. Patients with a mean aPTT ≥ 4 times ULN had higher rates recurrent ischaemic and haemorrhagic complications. After multivariable analyses, aPTT ratios ≥ 4 times ULN were no longer associated with recurrent ischaemic events, but remained a strong predictor of severe and moderate bleeding (hazard ratio [HR] 4.64, p = 0.016 and HR 2.27, p = 0.052). In conclusion, in 1,876 STEMI patients treated with pPCI, low aPTTs in the first 24 hours after PCI were not associated with an increase in ischaemic events, whereas high aPTT values were associated with more frequent bleeding complications. These results indicate no clear benefit as well as a safety concern with heparin treatment after primary PCI.

 
  • References

  • 1 Steg PG, James SK, Atar D. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 2012; 33: 2569-2619.
  • 2 O’Gara PT, Kushner FG, Ascheim DD. et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2012 epub ahead of print
  • 3 Antman EM. The Search for Replacements for Unfractionated Heparin. Circulation 2001; 103: 2310-2314.
  • 4 Kikkert WJ, Piek JJ, de Winter RJ. et al. Guideline adherence for antithrombotic therapy in acute coronary syndrome: an overview in Dutch hospitals. Netherl Heart J 2010; 18: 291-299.
  • 5 Camilleri JF, Bonnet JL, Bouvier JL. et al. Intravenous thrombolysis in myocardial infarction. Influence of the quality of the anticoagulation on the early recurrence rate of angina or infarction. Arch Mal Coeur Vaiss 1988; 81: 1037-1041.
  • 6 Kaplan K, Davison R, Parker M. et al. Role of heparin after intravenous thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1987; 59: 241-244.
  • 7 Granger CB, Hirsch J, Califf RM. et al. Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial. Circulation 1996; 93: 870-878.
  • 8 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.
  • 9 Anand SS, Yusuf S, Pogue J. et al. Relationship of Activated Partial Thromboplastin Time to Coronary Events and Bleeding in Patients With Acute Coronary Syndromes Who Receive Heparin. Circulation 2003; 107: 2884-2888.
  • 10 Nallamothu BK, Bates ER, Hochman JS. et al. Prognostic implication of activated partial thromboplastin time after reteplase or half-dose reteplase plus abciximab: results from the GUSTO-V trial. Eur Heart J 2005; 26: 1506-1512.
  • 11 Lee MS, Wali AU, Menon V. et al. The determinants of activated partial thromboplastin time, relation of activated partial thromboplastin time to clinical outcomes, and optimal dosing regimens for heparin treated patients with acute coronary syndromes: a review of GUSTO-IIb. J Thromb Thrombolysis 2002; 14: 91-101.
  • 12 Antman EM, Hand M, Armstrong PW. et al. 2007 Focused Update of the ACC/ AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction. Circulation 2008; 117: 296-329.
  • 13 Cutlip DE, Windecker S, Mehran R. et al. Clinical End Points in Coronary Stent Trials. Circulation 2007; 115: 2344-2351.
  • 14 The GUSTO investigators. An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction. N Engl J Med 1993; 329: 673-682.
  • 15 Suh JW, Mehran R, Claessen BE. et al. Impact of In-Hospital Major Bleeding on Late Clinical Outcomes After Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: The HORIZONS-AMI (Harmonizing Outcomes With Revascularisation and Stents in Acute Myocardial Infarction) Trial. J Am Coll Cardiol 2011; 58: 1750-1756.
  • 16 Hermanides RS, Ottervanger JP, Dambrink JH. et al. Suboptimal anticoagulation with prehospital heparin in ST-elevation myocardial infarction. Thromb Haemost 2011; 106: 636-640.
  • 17 Ferguson JJ, Dougherty KG, Gaos CM. et al. Relation between procedural activated coagulation time and outcome after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1994; 23: 1061-1065.
  • 18 Dougherty KG, Gaos CM, Bush HS. et al. Activated clotting times and activated partial thromboplastin times in patients undergoing coronary angioplasty who receive bolus doses of heparin. Catheter Cardiovasc Diagn 1992; 26: 260-263.
  • 19 Schulz S, Mehilli J, Neumann F-J. et al. ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention. Eur Heart J 2010; 31: 2482-2491.
  • 20 Vainer J, Fleisch M, Gunnes P. et al. Low-Dose Heparin for Routine Coronary Angioplasty and Stenting. Am J Cardiol 1996; 78: 964-966.
  • 21 Boccara A, Benamer H, Juliard J-M. 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.
  • 22 Liem A, Zijlstra F, Ottervanger JP. et al. High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial. J Am Coll Cardiol 2000; 35: 600-604.
  • 23 Koch KT, Piek JJ, de Winter RJ. et al. Safety of low dose heparin in elective coronary angioplasty. Heart 1997; 77: 517-522.
  • 24 Garachemani AR, Kaufmann U, Fleisch M. et al. Prolonged heparin after uncomplicated coronary interventions: A prospective, randomized trial. Am Heart J 1998; 136: 352-356.
  • 25 Rabah M, Mason D, Muller DWM. et al. Heparin after percutaneous intervention (HAPI): a prospective multicentre randomized trial of three heparin regimens after successful coronary intervention. J Am Coll Cardiol 1999; 34: 461-467.
  • 26 Friedman HZ, Cragg DR, Glazier SM. et al. Randomized prospective evaluation of prolonged versus abbreviated intravenous heparin therapy after coronary angioplasty. J Am Coll Cardiol 1994; 24: 1214-1219.
  • 27 The OASIS-6 Trial Group. Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial InfarctionThe OASIS-6 Randomized Trial. J Am Med Assoc 2006; 295: 1519-1530.
  • 28 Harjai KJ, Stone GW, Grines CL. et al. Usefulness of Routine Unfractionated Heparin Infusion Following Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction in Patients Not Receiving Glycoprotein IIb/IIIa Inhibitors. Am J Cardiol 2007; 99: 202-207.
  • 29 Stone GW, Witzenbichler B, Guagliumi G. et al. Bivalirudin during Primary PCI in Acute Myocardial Infarction. N Engl J Med 2008; 358: 2218-2230.
  • 30 Hibbert B, MacDougall A, Labinaz M. et al. Bivalirudin for Primary Percutaneous Coronary Interventions. Circulation Cardiovasc Interv. 2012 epub ahead of print
  • 31 Montalescot G, Zeymer U, Silvain J. et al. Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial. Lancet 2011; 378: 693-703.