PMID- 16380591
OWN - NLM
STAT- MEDLINE
DCOM- 20051230
LR  - 20161017
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 294
IP  - 24
DP  - 2005 Dec 28
TI  - Excess dosing of antiplatelet and antithrombin agents in the treatment of 
      non-ST-segment elevation acute coronary syndromes.
PG  - 3108-16
AB  - CONTEXT: Effective medical care assumes delivery of evidence-based medicines to 
      appropriate patients with doses comparable to those studied. OBJECTIVE: To 
      investigate dosing of unfractionated heparin (UFH), low-molecular-weight heparin 
      (LMWH), and glycoprotein IIb/IIIa inhibitors, and the association between dosing 
      and major outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective 
      observational analysis in 387 US academic and nonacademic hospitals of 30,136 
      patients from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina 
      Patients Suppress Adverse Outcomes With Early Implementation of the American 
      College of Cardiology/American Heart Association Guidelines) National Quality 
      Improvement Initiative Registry who had non-ST-segment elevation acute coronary 
      syndromes (NSTE ACS) with chest pain and either positive electrocardiograms or 
      cardiac biomarkers between January 1 and September 30, 2004. MAIN OUTCOME 
      MEASURES: Excessive dosing of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors and 
      major clinical outcomes, including bleeding, in-hospital mortality, and length of 
      stay. RESULTS: A total of 3354 patients (42%) with NSTE ACS who were administered 
      antithrombotic agents received at least 1 initial dose outside the recommended 
      range. An excess dose was administered to 2934 patients (32.8%) treated with UFH, 
      1378 (13.8%) treated with LMWH, and 2784 (26.8%) treated with glycoprotein 
      IIb/IIIa inhibitors. Factors associated with excess dosing included older age, as 
      well as female sex, renal insufficiency, low body weight, diabetes mellitus, and 
      congestive heart failure. Relative to those patients not administered excess 
      dosages, patients with excess dosages of UFH, LMWH, and glycoprotein IIb/IIIa 
      inhibitors either tended toward or had higher risks for major bleeding (adjusted 
      odds ratio [OR], 1.08; 95% confidence interval [CI], 0.94-1.26; OR, 1.39; 95% CI, 
      1.11-1.74; and OR, 1.36; 95% CI, 1.10-1.68; respectively). Bleeding increased 
      relative to the degree of excess dose and to the number of agents administered in 
      excess (6.6% [237/3590] if neither heparin nor glycoprotein IIb/IIIa excess vs 
      22.2% [93/419] if both excess). Mortality and length of stay were also higher 
      among those patients administered excess dosing. We estimated that 15% (400/2766) 
      of major bleeding in this population may be attributable to excess dosing. 
      CONCLUSIONS: Patients with NSTE ACS treated in the community often receive excess 
      doses of antithrombotic therapy. Dosing errors occur more often in vulnerable 
      populations and predict an increased risk of major bleeding.
FAU - Alexander, Karen P
AU  - Alexander KP
AD  - Duke University Medical Center, Duke Clinical Research Institute, Durham, NC 
      27715, USA. karen.alexander@duke.edu
FAU - Chen, Anita Y
AU  - Chen AY
FAU - Roe, Matthew T
AU  - Roe MT
FAU - Newby, L Kristin
AU  - Newby LK
FAU - Gibson, C Michael
AU  - Gibson CM
FAU - Allen-LaPointe, Nancy M
AU  - Allen-LaPointe NM
FAU - Pollack, Charles
AU  - Pollack C
FAU - Gibler, W Brian
AU  - Gibler WB
FAU - Ohman, E Magnus
AU  - Ohman EM
FAU - Peterson, Eric D
AU  - Peterson ED
CN  - CRUSADE Investigators
LA  - eng
GR  - R01 AG025312-01A1/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
RN  - 0 (Antithrombins)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 9005-49-6 (Heparin)
SB  - IM
EIN - JAMA. 2006 Feb 8;295(6):628
CIN - JAMA. 2006 Apr 26;295(16):1896-7; author reply 1897. PMID: 16639043
CIN - JAMA. 2006 Apr 26;295(16):1896; author reply 1897. PMID: 16639044
CIN - JAMA. 2006 Apr 26;295(16):1897; author reply 1897. PMID: 16639046
MH  - Aged
MH  - Angina, Unstable/*drug therapy
MH  - Antithrombins/*administration & dosage/adverse effects/therapeutic use
MH  - Female
MH  - Hemorrhage/etiology
MH  - Heparin/administration & dosage/therapeutic use
MH  - Heparin, Low-Molecular-Weight/administration & dosage/therapeutic use
MH  - Humans
MH  - Length of Stay
MH  - Male
MH  - Middle Aged
MH  - Platelet Aggregation Inhibitors/*administration & dosage/adverse 
      effects/therapeutic use
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors
MH  - Prospective Studies
MH  - Risk
MH  - Treatment Outcome
EDAT- 2005/12/29 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/12/29 09:00
PHST- 2005/12/29 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/12/29 09:00 [entrez]
AID - 294/24/3108 [pii]
AID - 10.1001/jama.294.24.3108 [doi]
PST - ppublish
SO  - JAMA. 2005 Dec 28;294(24):3108-16. doi: 10.1001/jama.294.24.3108.