LETTER TO THE EDITOR
Enoxaparin after high-risk coronary stenting
Javier Borja, MD*,
Jorge Curto, MStat,
Joaquin Campbell, BSci and
Marco A. Paz, MD
* Medical Department, Pharmacia Spain, S.A., Carretera de Rubí, 90-100, 08190 Sant Cugat del Vallés, Barcelona, Spain
javier.borja{at}pharmacia.com
We read with interest the report by Batchelor et al. (1), published in the November 15, 2001, issue of the Journal. They conclude that, given the relative safety of enoxaparin and the potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients. We would like to comment on some aspects of their study.
The investigators’ conclusion is based on the finding of a reduction of myocardial infarction at 30 days. This variable was neither the primary end point nor a predefined secondary end point in their study. The fact that the study was stopped prematurely owing to a low rate of events does not, in our opinion, allow one to conclude a therapeutic recommendation. Of course, it is possible that the end point was not achieved because of a beta error, as pointed out by the researchers, but we do not know what the outcome would be in a study including at least 3,590 patients, which was the recalculated sample size. Contrarily, Batchelor et al. (1) affirm that rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p = 0.08) were comparable. In reality, the rate of this event with enoxaparin was two times higher than with placebo, and the p value was next to the conventionally accepted significance level. In this case, the lack of statistical significance could also be due to a beta error, but this is omitted by the investigators.
Some aspects of the discussion deserve comment. It is mentioned that enoxaparin’s clinical superiority over unfractionated heparin (UFH) has been shown in patients with acute coronary syndromes (2–4) and that extended low-molecular-weight heparins (LMWHs) also reduce the short-term risk of thrombotic events, although benefits are not sustained at six months (5). In the same manner that it is mentioned that enoxaparin was superior to UFH, it should be specified that the benefit derived from extended LMWH use was obtained with dalteparin in the FRISC II study (5). Neither in the TIMI-11B (4) nor in the FRAXIS (6) studies, a benefit associated with the extended treatment of enoxaparin or fraxiparin, respectively, was not evidenced. As has been pointed out, LMWHs should not be regarded as interchangeable, but rather as distinct drugs with specific structural and functional profiles that require individual investigation (7). Thus, results obtained with one LMWH cannot be extrapolated to the other products.
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References
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1. Batchelor WB, Mahaffey KW, Berger PB, et al. A randomized, placebo-controlled trial of enoxaparin after high risk coronary stenting: the ATLAST trial. J Am Coll Cardiol. 2001;38:1608–1613[Abstract/Free Full Text]
2. Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events Study GroupCohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447–452[Abstract/Free Full Text]
3. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non–Q-wave myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI)-11B trial. Circulation. 1999;100:1593–1601[Abstract/Free Full Text]
4. Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxaparin for unstable angina/non–Q-wave myocardial infarction. TIMI-11B-ESSENCE meta-analysis. Circulation. 1999;100:1602–1608[Abstract/Free Full Text]
5. Fragmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) investigators. Long-term low-molecular-mass heparin in unstable coronary artery disease: FRISC II prospective randomised multicentre study. Lancet. 1999;354:701–707[CrossRef][Medline]
6. FRAXIS study group. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non–Q-wave myocardial infarction: FRAXIS (FRAXiparine in Ischaemic Syndrome). Eur Heart J. 1999;20:1553–1562[Abstract/Free Full Text]
7. Fareed J, Jeske W, Hoppenstead D, Clarizio R, Walenga JM. Are the available low-molecular-weight heparin preparations the same? Semin Thromb Hemost. 1999;22(Suppl 1):77–91
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