Enoxaparin dosing and associated risk of in-hospital bleeding and death in patients with non ST-segment elevation acute coronary syndromes

Arch Intern Med. 2007 Jul 23;167(14):1539-44. doi: 10.1001/archinte.167.14.1539.

Abstract

Background: The efficacy of enoxaparin sodium in non-ST-segment elevation acute coronary syndromes is well established; however, concerns remain regarding bleeding risk. The extent to which bleeding risk is attributable to excess dosing of enoxaparin is unclear.

Methods: Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) National Quality Improvement Initiative, we determined the frequency of administration of excess (>10 mg above the recommended dose), lower-than-recommended (>10 mg below the recommended dose), and recommended doses of enoxaparin. We also determined unadjusted and adjusted risks of in-hospital major bleeding and death associated with excess and lower-than-recommended doses of enoxaparin.

Results: Of 10 687 patients, 2002 (18.7%) received an excess dose and 3116 (29.2%) received a lower-than-recommended dose of enoxaparin. Patients receiving excess doses were older (median age, 78 vs 66 years), smaller (median body mass index [calculated as weight in kilograms divided by height in meters squared], 26.2 vs 27.8), and more likely to be female (59.5% vs 38.2%) than patients receiving recommended doses (P < .001 for all). After adjustment for baseline characteristics, an excess dose was significantly associated with major bleeding (odds ratio, 1.43; 95% confidence interval [CI], 1.18-1.75) and death (odds ratio, 1.35; 95% CI, 1.03-1.77) compared with a recommended dose. A lower-than-recommended dose was not associated with major bleeding (odds ratio, 1.01; 95% CI, 0.84-1.21), but there was a trend toward higher mortality (odds ratio, 1.25; 95% CI, 0.93-1.68).

Conclusions: Almost half the patients treated with enoxaparin did not receive a recommended dose and had worse outcomes, especially those receiving an excess dose. Improved adherence to the recommended dose could substantially improve the safety profile of enoxaparin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Disease / drug therapy*
  • Coronary Disease / mortality
  • Coronary Disease / physiopathology
  • Electrocardiography
  • Enoxaparin / administration & dosage*
  • Enoxaparin / adverse effects
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Hemorrhage / chemically induced*
  • Hospitalization
  • Humans
  • Male
  • Mortality

Substances

  • Enoxaparin
  • Fibrinolytic Agents