Current issues of ACP Journal Club are published in Annals of Internal Medicine


Enoxaparin had lower costs than unfractionated heparin for acute coronary syndrome

ACP J Club. 1998 Nov-Dec; 129:80. doi:10.7326/ACPJC-1998-129-3-080

Source Citation

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 May 5;97:1702-7. [PubMed ID: 9591764]



In patients with unstable angina or non-Q-wave myocardial infarction (MI), does subcutaneous enoxaparin (a low-molecular-weight heparin) have lower costs than intravenous unfractionated heparin?


Prospective economic substudy of the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events) trial, an international, multicenter, double-blind, randomized, controlled trial with follow-up at 30 days.


Study centers in the United States.


923 patients (median age 64 y, 65% men) who had recent onset of angina at rest lasting > 10 minutes within 24 hours of randomization and evidence of underlying ischemic heart disease. Exclusion criteria were contraindications to anticoagulation, advanced renal insufficiency, and unconfirmed procedures or hospitalizations on the patient's case report form. Hospital costs were imputed for 268 patients (29%) who did not have hospital billing data.


All patients received aspirin, 100 to 325 mg/d. 464 patients were allocated to enoxaparin, 1 mg/kg of body weight subcutaneously every 12 hours, and 459 patients were allocated to unfractionated heparin, 5000 U intravenous bolus followed by continuous infusion with serial adjustment. Drugs were given for 2 to 8 days.

Main cost and outcome measures

Main costs were mean medical cost (including hospital, physician, and drug costs) at initial hospitalization and cumulative cost to 30 days. Estimated total cost per patient was U.S. $155 ($69/d for mean 2.25 d) for enoxaparin and $80 for heparin. Study outcome was a composite end point of death, MI, or recurrent angina.

Main results

{Data from the full study sample (n = 3171 patients from 176 centers in North and South America and Europe) showed that the 30-day incidence of a composite measure of death, MI, or recurrent angina was lower for enoxaparin than for heparin (19.8% vs 23.3%, P = 0.02)}*. Total medical costs perpatient for enoxaparin and heparin did not differ at initial hospitalization($11 857 vs $12 620, P = 0.18), but the total cumulative cost savings per patient associated with enoxaparin at 30 days was $1172 (P = 0.04).


In U.S. patients with unstable angina or non-Q-wave myocardial infarction, enoxaparin had greater cumulative cost savings at 30 days than did unfractionated heparin.

Sources of funding: In part, Rhône-Poulenc Rorer and Agency for Health Care Policy and Research.

For correspondence: Dr. D.B. Mark, Box 3485, Duke University Medical Center, Durham, NC 27710, USA. FAX 919-286-4845.

*Cohen M, Demers C, Gurfinkel EP, et al. N Engl J Med. 1997;337:447-52.


The decision to use a new therapy requires evidence that the therapy improves patient outcomes and has sufficient clinical value to justify its cost. To address these 2 requirements at the same time, the protocols of many clinical trials now include an economic evaluation that tracks resource consumption and costs in randomized groups. The total cost includes the cost of the new therapy, as well as the cost of treating adverse effects (e.g., bleeding) and clinical complications (e.g., refractory symptoms or the need for coronary revascularization). When a therapy improves patient outcomes, the reduced cost of treating complications may offset some or all of the cost of the therapy. In the ESSENCE trial, enoxaparin cost an additional $75 per patient. This relatively modest incremental cost was entirely repaid by the decreased costs of coronary angiography and revascularization. In the U.S. clinical sites, where angiography is commonly done, there was a significant cost savings of $1172 at 30 days. The cost savings in non-U.S. sites was less ($493) because their already low rates of coronary angiography and revascularization provided less opportunity for further cost savings.

Should enoxaparin routinely replace unfractionated heparin in patients with unstable angina? Although the ESSENCE trial showed improved clinical and economic outcomes, guidelines should be based on more than 1 trial. In another trial on unstable angina, a different low-molecular-weight heparin (dalteprin) was no better than heparin (1). Low-molecular-weight heparins have been proved to be equal to or better than heparin in other conditions (2). The evidence suggests that low-molecular-weight heparins are at least as effective as heparin in patients with unstable angina, and their greater ease of administration justifies their small price premium (2).

Mark A. Hlatky, MD
Stanford University School of MedicineStanford, California, USA

Mark A. Hlatky, MD
Stanford University School of Medicine
Stanford, California, USA


1. Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in Unstable Coronary Artery Disease Study. Circulation. 1997;96:61-8. [PubMed ID: 9236418]

2. Weitz JI. Low-molecular-weight heparins. N Engl J Med. 1997;337:688-98. [PubMed ID: 9278467]