Unfractionated heparin dosing and risk of major bleeding in non–ST-segment elevation acute coronary syndromes

Melloni, Chiara; Alexander, Karen P.; Chen, Anita Y.; Newby, L. Kristin; Roe, Matthew T.; Allen LaPointe, Nancy M.; Pollack, Charles V.; Gibler, W. Brian; Ohman, E. Magnus; Peterson, Eric D.; for the CRUSADE Investigators,

doi:10.1016/j.ahj.2008.03.023

« Previous Next »American Heart Journal
Volume 156, Issue 2 , Pages 209-215, August 2008

Unfractionated heparin dosing and risk of major bleeding in non–ST-segment elevation acute coronary syndromes

Chiara Melloni, MD, MHS
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
- Reprint requests: Chiara Melloni, MD, MHS, 2400 Pratt St., Duke Clinical Research Institute, Durham, NC 27705.
Karen P. Alexander, MD
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
Anita Y. Chen, MS
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
L. Kristin Newby, MD, MHS
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
Matthew T. Roe, MD, MHS
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
Nancy M. Allen LaPointe, PharmD
- Division of Clinical Pharmacology, Duke University Medical Center, Durham, NC
Charles V. Pollack Jr, MD, MA
- Emergency Department, Pennsylvania Hospital, Philadelphia, PA
W. Brian Gibler, MD
- Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH
E. Magnus Ohman, MD
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
Eric D. Peterson, MD, MPH
- Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
for the CRUSADE Investigators

Received 13 December 2007; accepted 26 March 2008. published online 03 June 2008.

Background

Unfractionated heparin (UFH) is a mainstay of treatment for patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS), but the practice of weight-adjusted bolus and infusion dosing has not been carefully evaluated.

Methods

Using data from 31,445 high-risk patients with NSTE ACS enrolled at 420 hospitals in the CRUSADE initiative, we evaluated initial UFH dosing relative to guideline recommendations and determined factors associated with excess weight–adjusted dosing and major bleeding, overall and among subgroups. Excess dose was defined as >70 U/kg for bolus or >15 U/kg per hour for infusion.

Results

The most frequent bolus dose was 5,000 U (42.7%) and infusion dose was 1,000 U/h (46%). An excess weight–adjusted UFH bolus or infusion dose was administered 35% of the time. Factors strongly associated with excess weight–adjusted dosing were age (per 10-year increase) (odds ratio [OR] 1.11, 95% CI 1.08-1.15) and female sex (OR 1.45, 95% CI 1.33-1.59). Rate of major bleeding increased proportionally in relation to dose of UFH for both bolus and infusion, specifically when dose was above the recommended weight-adjusted range (>70 U/kg for bolus or >15 U/kg per hour for infusion). Both excess bolus (OR 1.03, 95% CI 1.00-1.06) and infusion (OR 1.16, 95% CI 1.05-1.28) were individually associated with increased bleeding. The relationship between weight-adjusted UFH dose and major bleeding did not vary independently by sex or age.

Conclusions

In high-risk patients with NSTE ACS, initial UFH bolus and infusion dosing were frequently higher than recommended weight-adjusted ranges, particularly in patients with lower body weight. Excess bolus and infusion rate dosing was associated with more bleeding and was common among elderly and females. Attention to dosing by weight rather than standard bolus and infusion dosing should lead to improved safety in the use of UFH.