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


Therapeutics

Enoxaparin reduced combined coronary events in unstable angina and non-Q-wave MI at 14 and 30 days

ACP J Club. 1998 Mar-April; 128:34. doi:10.7326/ACPJC-1998-128-2-034


Source Citation

Cohen M, Demers C, Gurfinkel EP, et al., for the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997 Aug 14; 337:447-52.


Abstract

Objective

To determine the efficacy and safety of enoxaparin (a low-molecular-weight heparin [LMWH]) compared with unfractionated heparin (UH) in patients with non-Q-wave coronary events (unstable angina or non-Q-wave myocardial infarction [MI]).

Design

Randomized, double-blind, placebo-controlled trial.

Setting

176 clinical centers in North and South America and Europe.

Patients

3171 men and nonpregnant women ≥ 18 years of age with recent-onset angina at rest lasting ≥ 10 minutes within 24 hours of randomization and evidence of underlying ischemic heart disease. Exclusion criteria were left bundle-branch block or pacemaker, persistent ST-segment elevation, angina with an established precipitating cause, contraindications to anticoagulants, or a low creatinine clearance rate.

Intervention

1564 patients were allocated to enoxaparin (1 mg/kg of body weight subcutaneously every 12 h), and 1607 patients were allocated to UH as an intravenous bolus (usually 5000 U) followed by a continuous infusion adjusted according to activated partial thromboplastin times of 55 to 85 seconds. Both groups received aspirin, 100 to 325 mg/d. Drugs were given for 2 to 8 days.

Main outcome measures

The main outcome was a composite end point of death, MI, or recurrent angina at 14 days. Secondary outcomes were the main outcome at 48 hours and 30 days; death or MI at 48 hours, 14 days, and 30 days; and major and minor hemorrhage.

Main results

Compared with those who received UH, patients who received enoxaparin had a lower rate of the composite end point at 14 and 30 days (P = 0.02 for both) (Table). They also had lower rates of total revascularization (27.0% vs 32.2%, P = 0.001) and percutaneous revascularization (14.7% vs 18.7%, P = 0.002) and a higher rate of minor hemorrhage (11.9% vs 7.2%, P < 0.001).

Conclusion

Enoxaparin led to fewer combined coronary events than unfractionated heparin in patients with non-Q-wave coronary artery disease.

Source of funding: Rhône-Poulenc Rorer Corporation.

For article reprint: Dr. M. Cohen, Division of Cardiology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Mail Stop-119, Philadelphia, PA 19102, USA. FAX 215-246-5488.


Table. Combined coronary events with enoxaparin vs unfractionated heparin*

Time after event Enoxaprin EER Unfractionated heparin CER RRR (95% CI) ARR |EER-CER| NNT (CI)
14 d 16.6% 19.7% 16.1% (2.8 to 27.8) 3.2% 31 (17 to 191)
30 d 19.8% 23.3% 15% (2.9 to 25.6) 3.5% 29 (16 to 160)

*Abbreviations defined in Glossary; RRR, ARR, NNT, and CI calculated from data in article.


Commentary

Many countries have replaced standard heparin with LMWHs for treatment of acute coronary syndromes because the latter produce more predictable anticoagulation, are less likely to be inhibited by platelet factors, induce thrombocytopenia less often (1), are given only twice daily, and require no monitoring.

2 LMWHs (dalteparin and enoxaparin) have been studied in large trials of non-ST-segment elevation in acute coronary syndromes (1). In a double-blind, placebo-controlled trial of 1506 patients, fewer deaths or MIs occurred (1.8% vs 4.8%, P = 0.001) at 6 days but not at 40 days (8.0% vs 10.7%, P = 0.07) among those receiving dalteparin (2). The 6-day composite of death, MI, or recurrent angina did not differ in another study of dalteparin compared with standard heparin in 1499 patients (9.3% vs 7.6%, P = 0.42) (3). The study by Cohen and colleagues represents the largest trial of LMWH (enoxaparin) in this population. Most of the treatment effect reflected the relative reduction of MI at 14 days. These 3 studies suggest that LMWHs are at least equivalent and perhaps slightly superior to standard heparin for prevention of these events.

Should these studies change practice patterns? Where patients with acute coronary syndromes are treated conservatively, the answer is "yes," given the better outcomes and fewer angioplasties done when patients receive LMWHs. Where early angioplasty is common (< 2 d after admission), there is less incentive for change, particularly given the higher costs. This may change if LMWHs can be combined with platelet glycoprotein IIb/IIIa inhibitors, which also reduce events in patients with acute coronary syndromes. This combination is attractive, but much work remains to further reduce death and MI in these patients.

E. Magnus Ohman, MD
Duke University Medical CenterDurham, North Carolina, USA


References

1. Weitz JI. Low-molecular-weight heparins. N Engl J Med. 1997;337:688-98.

2. FRagmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet. 1996;347:561-8.

3. 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.