Enoxaparin sodium

To the Editor:

We wish to challenge the statement in the review of antithrombotic agents for use in coronary artery disease by Cairns et al (1(p241S)) that, compared with unfractionated heparin, the treatment of unstable coronary artery disease with enoxaparin produces significant cost savings only in hospitals in the United States and not in the hospitals of other countries. In fact, a number of peer-reviewed articles have demonstrated that treatment of this condition with enoxaparin produces significant cost savings in hospitals in countries other than the United States, including Canada, South America, the United Kingdom, and France.

Based on the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial, (2) use of enoxaparin instead of unfractionated heparin resulted in a significant in-hospital and 30-day cost saving in US patients (Table 1). (3) Similar results were seen at 30 days in the French (4) and Argentina/Uruguay (5) subgroups of the ESSENCE trial. Further, a Canadian predictive decision-analysis model confirmed that enoxaparin was the least costly strategy for the majority of 30-day composite end point values. (6) Finally, based in part on the continued advantage of enoxaparin over unfractionated heparin at 1 year follow-up, (7) both UK (8) and Canadian (9) cost-effectiveness analyses predicted impressive cost savings with enoxaparin. Thus, in addition to greater clinical efficacy observed in the ESSENCE trial and recently confirmed in other studies, (10-12) use of enoxaparin led to both lower administrative costs (less use of IV sets, IV infusion pumps, and nursing time) and decreased resource utilization (fewer cardiac catheterizations, coronary revascularizations, shorter length of hospital stay). Despite the modestly higher drug acquisition cost, these advantages translated into observed cost savings with enoxaparin as compared to unfractionated heparin in several different countries. In addition, it should be noted that all the studies mentioned have only considered direct costs and have not included indirect costs (such as loss of work time, and increased costs incurred by patients), and thus it is possible to speculate on further savings to society were these costs analyzed.

The consistent results from these analyses lead us to conclude that the treatment of unstable coronary artery disease with enoxaparin is less costly than treatment with unfractionated heparin, not only in the United States but also other clinical practice settings and countries in the world. We suggest that an erratum should be published, and that the results from these studies should be considered when the American College of Chest Physician guidelines for antithrombotic therapy are next updated.

Correspondence to: Keith A. A. Fox, MB ChB, FRCP, Department of Cardiology, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, EH3 9YW, UK; e-mail: k.a.a.fox@ed.ac.uk

REFERENCES

(1) Cairns JA, Theroux P, Lewis HD, et al. Antithrombotic agents in coronary artery disease. Chest 2001; 119:228S-252S

(2) Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfraetionated heparin for unstable coronary artery disease: Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337:447-452

(3) Mark DB, Cowper PA, Berkowitz SD, et al. Economic assessment of low-molecular weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Circulation 1998; 97:1702-1707

(4) Detournay B, Huet X, Fagnani F, et al. Economic evaluation of enoxaparin sodium versus heparin in unstable angina: a French sub-study of the ESSENCE trial. Pharmacoeconomics 2000; 18:83-89

(5) Bozovich G, Gurfinkel E, Barreiro D, et al. Reduction of hospital costs for patients with acute non-Q-wave myocardial infarction or unstable angina treated with enoxaparin compared to standard heparin [abstract]. Eur Heart J 1999; 20:545

(6) Balen RM, Marra CA, Zed PJ, et al. Cost-effectiveness analysis of enoxaparin versus unfractionated heparin for acute coronary syndromes: a Canadian hospital perspective. Pharmacoeconomics 1999; 16(5 pt 2):533-542

(7) Goodman S, Cohen M, Bigonzi F, et al. Randomised trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one year results of the ESSENCE study. J Am Coll Cardiol 2000; 36:693-698

(8) Bosanquet N, Fox KAA. Longer term economic benefits reflect-improved clinical outcomes with enoxaparin versus unfractionated heparin in acute coronary syndromes: one-year data. Br J Cardiol 2001; 8:36-37

(9) O'Brien BJ, Willan A, Blackhouse G, et al. Will the use of low-molecular-weight heparin (enoxaparin) in patients with acute coronary syndrome save costs in Canada? Am Heart J 2000; 139:423-429

(10) Antman E, 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

(11) 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

(12) Antman EM, Cohen M, McCabe C, et al. Enoxaparin is superior to unfractionated heparin for preventing clinical events at i-year follow-up of TIMI lib and ESSENCE. Eur Heart J Ideal First Articles 2001. Available at: http://www. idealibrary.com/links/doi/10.1053/euhj.2001.2779. Accessed January 3, 2002.

To the Editor:

The study of Mark et al (1) was based on the 655 US patients with available economic data, out of the total of 936 US patients in the Efficacy and Safety of Subcutaneous Enoxaporin in Non-Q-Wave Coronary Events (ESSENCE) trial. The overall cost reduction associated with enoxaparin use was statistically significant at 30 days among the US patients. Amongst the total study cohort, there was a trend toward reduced costs, but it was not statistically significant. These data underlay our statement that "an economic assessment of the ESSENCE results showed significant cost savings in US hospitals, but not across those in other countries with the cost saving mainly attributable to fewer cardiac catherization procedures."

Fox and Goodman, in their letter, refer to economic analyses of non-US national subpopulations drawn from the ESSENCE trial, the results of which are consistent with the nonsignificant trend toward cost savings with enoxaparin use reported in the article to which we referred. (1) Although the outcome data for the TIMI 11b trial (references 10, 11, and 12 in their letter all relate to this trial) are similar to those in the ESSENCE trial, we are not aware of any published procedural data or economic analyses based on this trial.

Correspondence to: John A. Cairns, MD, Dean, Faculty of Medicine, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada

REFERENCE

(1) Mark DB, Cowper PA, Berkowitz SD, et al. Economic assessment of low molecular weight heparin (enoxatparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (unstable angina or non-Q-wave myocardial infarction). Circulation 1998; 97:1702-1707

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