Dosing of LMW Heparin in Obesity Indications
Six trials were identified that documented dosing of LMW heparin in obese patients with venous thromboembolism and other indications. One of these trials compared once-daily and twice-daily nadroparin for treatment of this condition. In that study, patients weighing more than 90 kg each received 18 450 IU of nadroparin (maximum body weight 120 kg). Because the study included no comments on the impact of obesity on patients’ outcomes, this study was excluded from the current review. The remaining 5 trials are summarized in Table 4.
The Enoxaparin Clinical Trial Group compared enoxaparin doses of 1.5 mg/kg once daily or 1 mg/kg twice daily with adjusted-dose IV unfractionated heparin. Of the 900 patients enrolled in the study, 405 were obese (defined on the basis of BMI). Among the patients who received enoxaparin, weight ranged from 44 to 155 kg. Subgroup analysis indicated that cancer and symptomatic pulmonary embolism were significant risk factors for recurrent venous thromboembolism in all 3 treatment groups. Obesity was also a significant risk factor for recurrence for the 2 enoxaparin-treated groups. A nonsignificant trend toward recurrence with once-daily enoxaparin was observed at 3 months among obese patients: 7.3% for once-daily and 3.4% for twice-daily dosing (p = 0.18 by 2-sided Fisher’s exact test). On the basis of these results, some have advocated twice-daily dosing of enoxaparin for obese patients.
In 2 small trials, dalteparin was administered without a dose cap for obese patients; the surrogate end point examined was anti-Xa levels. In the first of these studies, a review of obese patients receiving dalteparin for bridging therapy, samples were drawn from 21 patients for measurement of anti- Xa levels 4 h after the second or third dose. In 2 of the 21 patients, the anti-Xa level was above the target range; both of these patients were receiving 100 U/kg twice daily. In 4 of the patients, anti-Xa was below the target range; all of these patients were receiving 200 U/kg once daily. The duration of therapy and patient outcomes were not reported. buy cialis soft tabs
A group from Nova Scotia examined patients receiving a minimum of 5 days of dalteparin therapy for venous thromboembolism. The mean duration of therapy was about 6.5 days. The authors grouped patients into 3 categories on the basis of degree of obesity. LMW heparin doses were not capped, and dosages ranged from 11200 to 38 000 U/day. There was no difference in anti-Xa levels among the 3 groups at any of the time points. Overall, peak anti-Xa levels tended to be low for once-daily dosing.
The outcomes for obese patients receiving dalteparin for acute venous thromboembolism were reported in a retrospective study from Ontario. About 5% of the patients weighed more than 150 kg. By the end of the 3-month follow-up period, 2 patients had experienced an episode of major bleeding, both of which occurred long after the course of dalteparin had been completed. One of the 3 recurrent thromboembolic events occurred within the first month of therapy. The authors concluded that dalteparin could be administered for acute venous thromboembolism, at full treatment doses and without a dose cap, without increasing the risk of major hemorrhage. viagra 50 mg
A Spanish registry study evaluated clinical outcomes over 15 days among patients with a diagnosis of venous thromboembolism according to 3 weight categories.28 Two hundred and ninety-four patients in the registry weighed more than 100 kg (mean weight 112 kg, range 101-160 kg). The mean daily dose (± standard deviation) of the unspecified LMW heparins was 148 ± 36 IU/kg for patients weighing more than 100 kg, with 74% of these patients receiving less than 175 IU/kg. Some of the study sites used a cap on the LMW heparin dose. No statistically significant difference in recurrent venous thromboembolism or major bleeding was observed between the weight groups.
Of the 6 trials of LMW heparins for venous thromboembolism and other indications, only 5 trials (involving enoxaparin and dalteparin) provided evaluable data. The trial of enoxaparin included a subgroup analysis of a larger group and evaluated 2 different dosage regimens. In that study, no dose cap was used and there was no increase in the rate of bleeding. The best data regarding LMW heparins in obesity for these indications are for dalteparin. Both the retrospective evaluation from Ontario and the 2 studies using anti-Xa levels as a surrogate end point suggest that efficacy and safety are not compromised by dosing dalteparin according to actual body weight.
Few obese patients have been enrolled in the major trials of LMW heparins for treatment of venous thromboembolism.
A 2001 review of LMW heparins in special populations concluded that the dosage of LMW and body surface area or BMI may correlate with anti-Xa activity, bleeding, and thromboembolic outcomes. The authors of the review recommended that the dose of LMW heparins be calculated according to total body weight in kilograms. In that review, the highest reported total body weights for patients receiving treatment for acute venous thromboembolism were 159 kg with enoxaparin and 190 kg with dalteparin.