To the Editor: Dr Alexander and colleagues1 studied excess dosing of antithrombotic therapy in patients with non–ST-segment elevation acute coronary syndromes. We support their conclusions that this occurs frequently and is associated with major bleeding. However, it is possible that the finding of a nonsignificant adjusted odds ratio for any excess dose of unfractionated heparin (1.08; 95% confidence interval, 0.94-1.26), which was also lower than that for other antithrombotic agents, was primarily related to the inherent difficulty in defining an excess dose regimen.
Because of its highly variable pharmacokinetics and anticoagulant effect, the optimal dose of unfractionated heparin requires careful adjustments according to the activated partial thromboplastin time (aPTT) instead of body weight.2 A weight-based cutoff may not accurately differentiate among patients administered appropriate, excess, or inadequate doses of unfractionated heparin. Furthermore, despite strict adherence to dose titration nomograms in clinical trials, substantial fluctuations in aPTT are common within the first 24 hours of treatment.3 Therefore, both excess dosing and underdosing of unfractionated heparin are likely more prevalent in the “real world,” where monitoring of aPTT may be less rigorous than in a study setting, and the true risk of serious bleeding complications due to an excess dose (as defined by aPTT above the therapeutic range) may be higher than reported.
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) registry may also provide valuable insights into bleeding risk assessment and its treatment implications. It would be important to determine whether there was an interaction effect on major bleeding between excess doses of antithrombotic therapy and the early invasive strategy, which has been increasingly adopted in contemporary practice.
Financial Disclosures: Dr Goodman has received speaker and consulting honoraria and research grants from Aventis, Key Schering, and Millennium Pharmaceuticals. Drs A. Yan and R. Yan reported no financial disclosures.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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