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CC BY 4.0 · Thromb Haemost 2018; 118(07): 1250-1256
DOI: 10.1055/s-0038-1657768
New Technologies, Diagnostic Tools and Drugs
Georg Thieme Verlag KG Stuttgart · New York

Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study)

Wael Sumaya
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
William A. E. Parker
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Rebekah Fretwell
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
,
Ian R. Hall
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
David S. Barmby
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
James D. Richardson
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Javaid Iqbal
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Zulfiquar Adam
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Kenneth P. Morgan
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
,
Julian P. Gunn
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Annah E. Mason
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Heather M. Judge
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
,
Christopher P. Gale
3   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
,
Ramzi A. Ajjan
3   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
,
Robert F. Storey
1   Department of Infection, Immunity and Cardiovascular Disease, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom
2   South Yorkshire Cardiothoracic Centre, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
› Author Affiliations Funding This study was funded through a British Heart Foundation clinical research training fellowship for Dr Wael Sumaya (FS/15/82/31824).
Further Information

Publication History

29 January 2018

26 April 2018

Publication Date:
06 June 2018 (online)

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Abstract

Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2–3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y12 inhibition.

Keywords

STEMI - primary PCI - enoxaparin - P2Y12 inhibition - stent thrombosis

Supplementary Material

 

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