In evaluating the issue of dosing caps for LMW heparins, there is a paucity of data from which to draw conclusions. Assessment of this issue is dependent on data primarily from pharmacokinetic studies in healthy volunteers, post hoc or subgroup analyses from trials of acute coronary syndromes and venous thromboembolism, and small clinical trials using anti-Xa levels as a surrogate marker of efficacy. Given the prevalence of obesity, it would be helpful if more literature were available on dosing of LMW heparins in obese patients.
The best outcome data reviewed here were for the use of LMW heparins in acute coronary syndromes. The review by Spinler and others of enoxaparin use in the ESSENCE and TIMI 11B trials is the largest of these. For more than 900 obese patients, there was no evidence that dosing of enoxaparin according to total body weight, without a dose cap, increased the rate of bleeding relative to IV unfractionated heparin. The authors of the review suggested that obese patients with acute coronary syndromes who were treated with enoxaparin had better outcomes than those treated with unfractionated heparin, but to our knowledge, this result has not been confirmed for treatment doses capped at 120 kg. canadian pharmacy viagra
Both of the small-scale trials that examined peak anti-Xa levels in obese patients treated with dalteparin drew similar conclusions. In one study, the patients were receiving bridging therapy, and in the other the treatment was for venous thromboembolism. Although these 2 trials had design limitations (e.g., small numbers, open-label, no event rates), both supported the removal of a dose cap to achieve target peak anti-Xa levels. There was no evidence of excessive accumulation without a dose cap.
In a Pharmacia newsletter published in 2001, the manufacturer stated that “experience with a maximum daily-dose of 18 000 aXaU [units] in pivotal studies has shown similar effectiveness and tolerability in patients >90 kg as compare [sic] with patients < 90 kg, therefore, from an efficacy standpoint giving more than 18 000 IU per day would not be expected to improve outcomes”. However, this comment was not referenced in the newsletter.