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CLINICAL RESEARCH: THERAPY OF CORONARY ARTERY DISEASE

Recurrent cardiac ischemic events early after discontinuation of short-term heparin treatment in acute coronary syndromes

Results from the thrombolysis in myocardial infarction (TIMI) 11B and efficacy and safety of subcutaneous enoxaparin in Non–Q-Wave coronary events (ESSENCE) studies

Nick R. Bijsterveld, MD^*, Ron J. G. Peters, MD^*,*, Sabina A. Murphy, MPH, Peter J. L. M. Bernink, MD, Jan G. P. Tijssen, PhD^*, Marc Cohen, MD, FACC TIMI 11B/ESSENCE Study Groups

^* Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
TIMI Data Coordinating Center, Boston, Massachusetts, USA
Department of Cardiology, Martini Hospital, Groningen, The Netherlands
Department of Cardiology, Newark Beth Israel Medical Center, Newark, New Jersey, USA

Manuscript received December 20, 2002; revised manuscript received April 11, 2003, accepted May 20, 2003.

^* Reprint requests and correspondence: Dr. Ron J. G. Peters, Department of Cardiology, Room F3-236, Academic Medical Center, Meibergdreef 9, 1105 AZ, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
R.J.Peters{at}amc.uva.nl

OBJECTIVES: The aim of this study was to determine whether discontinuation of low-molecular-weight heparin (LMWH) treatment results in a clustering of cardiac ischemic events as previously observed after cessation of unfractionated heparin (UFH) in acute coronary syndrome (ACS) patients.

BACKGROUND: Clinical trials in patients with ACS have shown early recurrent ischemic events after discontinuation of UFH treatment. We analyzed whether LMWH cessation also results in early ischemic recurrence events and if continuation of a fixed-dose LMWH prevents this complication.

METHODS: The combined incidence of death, myocardial infarction, or urgent revascularization in the first seven days after discontinuation of UFH (n = 3,012), short-term enoxaparin 1 mg/kg subcutaneously twice a day (n = 2,011), and short-term enoxaparin followed by prolonged enoxaparin 60 mg subcutaneously twice a day (n = 1,075) was analyzed from the combined Thrombolysis In Myocardial Infarction (TIMI) 11B/Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events (ESSENCE) database in a per patient analysis.

RESULTS: The cessation of both UFH and short-term enoxaparin resulted in a similar clustering of recurrent ischemic events on the first day, with an incidence of the primary end point of 2.8% in both groups. Of all recurrent events in the first week after cessation, 40% occurred in the first 24 h. The continuation of a fixed-dose enoxaparin treatment prevented this early excess, with a first day incidence of 0.4% (p < 0.0001). The TIMI risk score characteristics predicted the incidence of early rebound ischemic events.

CONCLUSIONS: There is significant clustering of recurrent ischemic events within 24 h after cessation of both short-term UFH and enoxaparin treatment, and patients should be carefully monitored during that period. This early rebound may be prevented by continuation of a fixed dose of enoxaparin.

Abbreviations and Acronyms   ACS = acute coronary syndromes   CI = confidence interval   ESSENCE = Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events   LMWH = low-molecular-weight heparin   LongEnox = long-term out-hospital continuation of enoxaparin treatment   MI = myocardial infarction   OR = odds ratio   ShortEnox = short-term in-hospital enoxaparin treatment   TIMI = Thrombolysis In Myocardial Infarction   UFH = unfractionated heparin

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