Unfractionated Heparin Dosing in the FRIC Study
To the Editor:
In the recent FRIC study,1 the subheading on page 65 states “Anti–Factor Xa Activity and aPTT Values in the Acute Phase,” but no activated partial thromboplastin time (aPTT) values were provided. Because one of the measures of performance of unfractionated heparin (UFH) dosing is the aPTT achieved, the reader cannot interpret the degree of anticoagulation achieved with UFH if no aPTT values are provided. Because aPTT measurement was mandated per protocol at 6 and 12 hours as well as daily through 48 hours, these median aPTT values should be reported as well as the percentages of patients below and above the target of aPTT of 1.5 times the control value. If dalteparin at a dose of 120 IU/kg twice daily is as good as poorly dosed UFH with no safety advantages, why would one use the more expensive dalteparin?
A separate issue relating to all multicenter studies of anticoagulants that use one mandated range for aPTT measurement (such as 1.5 times control) relates to the lack of standardization of the aPTT ranges to target UFH concentrations as well as variability among reagents used for aPTT measurement at individual centers when the target range is only expressed in seconds (eg, 60 to 85 seconds). Both inconsistencies with aPTT measurement could lead to uninterpretable results with UFH. If all new, more expensive anticoagulants are to be compared with UFH, closer scrutiny of dosing is warranted.
- Copyright © 1998 by American Heart Association
Klein W, Buchwald A, Hillis SE, Mohiad S, Sanz G, Turpie AGG, van der Meer J, Olaisson E, Undeland S, Ludwig K. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation. 1997;96:61–68.
The median aPTT values in the acute phase of the FRIC trial were as follows (Table 1⇑ ):
Therefore the median aPTT was ≈60 seconds for days 1 to 3 and maintained to around 45 seconds for days 4 to 7. The median length of the heparin infusion was 51 hours and the median total length of heparin treatment (intravenous only or intravenous plus subcutaneous) was 6 days. From a clinical perspective this must be considered sufficient heparin treatment with aPTT levels as a tool for monitoring. This is also reflected in a rather low number of ischemic events after 48 hours in the heparin arm of the FRIC trial.
In addition, we have calculated how many patients were within (1.5 to 2.0 times the local reference value), below, or above these limits. The results are shown in Table 2⇑ :
Approximately 50% of the patients achieved the desired target range during days 1 to 7. However, during days 1 to 3, 20% were below the desired range and levels were maintained below an average of 40% for days 4 to 7.
Finally, it should be mentioned that the use of low-molecular-weight heparin by the subcutaneous route provides the potential of simple, effective delivery of anticoagulation with enhanced convenience without the costs of staff, infusion equipment, and aPTT monitoring associated with intravenous unfractionated heparin. The simplicity of dosing and lack of toxicity of subcutaneous low-molecular-weight heparin allow unstable patients to be treated in a low-cost environment while infarction is ruled out, such as in accident or emergency holding wards or general medical wards rather than in a coronary care unit setting only.