LETTER TO THE EDITOR
Enoxaparin for acute coronary syndromes?
Christoph Pechlaner, MDa,
Walter Gritsch, MDa and
Christian Wiedermann, MDa
a Innsbruck University Hospital, Medical Intensive Care Unit, Anichstr. 35, A-6020 Innsbruck, Austria
christoph.pechlaner{at}uibk.ac.at
Goodman et al. (1) conclude that enoxaparin is a more effective antithrombotic treatment than unfractionated heparin (UFH) for the prevention of rebound ischemia in patients with unstable angina or non-Q-wave myocardial infarction. We suggest an alternative conclusion.
Enoxaparin’s plasma half-life is two to four times longer as compared to UFH after subcutaneous administration (2), even more when compared to UFH given intravenously, as in the Goodman et al. study. Activity against factor Xa and thrombin disappears only after more than 16 h (3), following moderate doses of enoxaparin. With high doses, as used in the ESSENCE study (1), enoxaparin’s plasma half-life is substantially longer (4).
Therefore, after stopping study drugs in the ESSENCE study, enoxaparin’s antithrombotic effect very likely lasted much longer than that of UFH. After stopping UFH, ischemic events during the 48-h monitoring period were twice as frequent as after stopping enoxaparin (45% vs. 26%), whereas there was no difference while on active treatment (25%)—compatible with an antithrombotic effect lasting about one day longer after enoxaparin. In addition, enoxaparin’s antithrombotic effect wanes much more slowly as compared to IV UFH. This may have added benefit by attenuating a heparin rebound effect.
It remains to be convincingly shown whether enoxaparin or other low-molecular-weight heparins exert superior antithrombotic effects as compared to UFH. Superior clinical benefit might be explained by pharmacokinetic differences only. For patients with acute coronary syndromes, extending the duration and slower weaning (5) of IV UFH may well be better and cheaper.
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References
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- Goodman SG, Barr A, Sobtchouk A, et al. Low molecular weight heparin decreases rebound ischemia in unstable angina or non-Q-wave myocardial infarction: the Canadian ESSENCE ST Segment Monitoring Substudy. J Am Coll Cardiol. 2000;36:1507–1513[Abstract/Free Full Text]
- Weitz JI. Low-molecular-weight heparins. N Engl J Med. 1997;337:688–698[Free Full Text]
- Agnelli G, Iorio A, Renga C, et al. Prolonged antithrombin activity of low-molecular-weight heparins. Clinical implications for the treatment of thromboembolic diseases. Circulation. 1995;92:2819–2824[Abstract/Free Full Text]
- Dawes J. Comparison of the pharmacokinetics of enoxaparin (Clexane) and unfractionated heparin. Acta Chir Scand. 1990;556(Suppl):68–74
- Becker RC, Spencer FA, Li Y, et al. Thrombin generation after the abrupt cessation of intravenous unfractionated heparin among patients with acute coronary syndromes: potential mechanisms for heightened prothrombotic potential. J Am Coll Cardiol. 1999;34:1020–1027[Abstract/Free Full Text]
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