Antiplatelet and Antithrombin Dosing Too High
January 3, 2006
Over 40% of patients with non-ST-segment elevation acute coronary syndromes received incorrect doses of antiplatelet or antithrombin drugs, according to a recent observational study. Most of the dosing errors involved doses above the recommended levels.
The study by Karen P Alexander, MD, of the Duke Clinical Research Institute, and colleagues, was published in the Journal of the American Medical Association and reported by MedPage Today on 27 December 2005.
Clinical Trial
The trial was a prospective, observational analysis of data from 378 US academic and non-academic hospitals. The drugs observed were unfractionated heparin, low-molecular weight heparin and glycoprotein IIb/IIIa inhibitors.
From 1 January through to 30 September 2004, 30,136 patients were admitted.
In total, 42% of patients received at least one initial dose of the relevant drugs that was outside recommended dosing ranges. Excess dosing errors occurred more often in medically vulnerable subgroups, including women, the elderly and people with renal insufficiency, low body weight, diabetes mellitus or congestive heart failure.
The observed patient population consisted of people already at increased risk of bleeding. These patients were thus in "double jeopardy" of developing bleeding complications, the researchers wrote, reported MedPage Today.
Dr Alexander and colleagues drew findings from the National Quality Improvement Initiative Registry of 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).
The study found that excess doses of antiplatelets or antithrombins were given to:
- 32.8% of people treated with unfractionated heparin.
- 13.8% of people treated with low-molecular-weight heparin.
- 26.8% of people treated with glycoprotein IIb/IIIa inhibitors.
Effects of Incorrect Dosing
The observed dosing errors were associated with predictable outcomes; people who received excess doses either tended to have or had a higher risk of major bleeding:
- Unfractionated heparin - Odds ratio = 1.08 (95% confidence interval , 0.94-1.26)
- Low-molecular-weight heparin-Odds ratio = 1.39 (95% CI, 1.11-1.74).
- Glycoprotein IIb/IIIa inhibitors- Odds ratio = 1.36 (95% CI , 1.10-1.68).
The researchers estimated 15% (400/2766) of major bleeding events in the trial population may have been attributable to excess dosing.
Reasons for Excess Dosing
Why the excess dosing? According to the researchers, physicians may contribute to drug errors by adopting a standardized dosing approach, or by underestimating the importance of staying within the recommended dosing range. Equally significant, important information may be unavailable when orders are written, the authors suggest.
Renal function must be clearly assessed, also, and using serum creatinine to gauge renal function is easy but not always accurate. Elderly patients in particular may have near-normal serum creatinine levels, yet have significant renal impairment.
And if weight measurements are not available, heavy patients may be under-dosed and lighter patients may receive too much medication.
"By ensuring creatinine clearance and weight are available at admission, some aspects of dosing accuracy may be improved," the authors said.
The authors noted limitations of the study that may have caused the problem of incorredct dosing to be underestimated, including the fact that "completeness and accuracy of the CRUSADE database was high in an audited sample, but events are not adjudicated and underreporting is possible. These factors, if anything, would lead to an underestimation of dosing errors as well as their association with adverse clinical outcomes."
Sources:
Dosing Of Antiplatelet And Antithrombin Drugs Often Too High,
MedPage Today, 27 December 2005.
Excess
Dosing of Antiplatelet and Antithrombin Agents in the Treatment of
Non-ST-Segment Elevation Acute Coronary Syndromes. Alexander KP
et al, Journal of the American Medical Association, volume
294, pages 3108-3116, 2005.
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