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Author's Reply
Submit responseWe appreciate the analyses by Dr. Umscheid of a subgroup of the studies which were included in the systematic reviews which we identified. These analyses confirm that there is little difference in outcomes (both efficacy and safety outcomes) between weight-based UFH and weight-based LMWH. We expect that practice patterns have changed since the publication of most of these trials; it is usual practice in most institutions to use a weight-based nomogram for intravenous heparin dosing. We are pleased that Dr. Umscheid’s analyses support the recommendations in the guidelines in this current era of weight-based dosing of both UFH and LMWH.
Conflict of Interest:
None declared
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Comparing Apples to Apples: Weight-based LMWH vs. Weight-based IV UFH
Submit responseIn regards to the systematic review evaluating the management of venous thromboembolism (VTE) by Segal et al.(1), we are concerned that the analyses comparing the efficacy and safety of low molecular weight heparin (LMWH) to unfractionated heparin (UFH) are biased against UFH. In 1993, Raschke et al. demonstrated the superior efficacy and safety of the weight-based UFH dosing nomogram compared to the traditional non-weight-based UFH dosing nomogram for the treatment of VTE.(2) But of the approximately 45 studies included in Segal's review, only 6 (13%) compared weight-based LMWH to weight-based intravenous (IV) UFH. Comparing weight-based LMWH to non-weight-based UFH would result in a bias against the efficacy of UFH in heavier patients and against the safety of UFH in lighter patients.
Using the six studies above, we compared outcomes at 90 to 100 days of using weight-based LMWH versus weight-based IV UFH for the treatment of VTE. Where appropriate, we used random-effects meta-analyses to combine relative risks from individual studies, and measured heterogeneity using the Q statistic. We found no statistical differences in major bleeding, mortality or recurrent VTE between patients receiving weight-based LMWH versus weight-based IV UFH, regardless of patient population or LMWH dosing (Table). No significant heterogeneity was demonstrated. A limitation of our analyses is our lower sample sizes as compared to the "Cluster C" analyses by Segal et al. (1), which included at least 5,568 patients.
Ultimately, our recommendation for the management of VTE may have been similar to Snow et al. (3), but our support of LMWH over IV UFH would be based on concerns regarding the lesser effectiveness or higher indirect costs associated with the titration of IV UFH, rather than its efficacy.
1. Segal JB et al. Management of venous thromboembolism: A systematic review for a practice guideline. Ann Intern Med 2007 Feb 6; 146:211-22.
2. Raschke RA et al. The weight-based heparin dosing nomogram compared with a “standard care” nomogram: a randomized controlled trial. Ann Intern Med 1993 Nov 1; 119:874-881.
3. Snow V et al. Management of venous thromboembolism: A clinical practice guideline from the
Table. Outcomes associated with weight-based LMWH versus weight-based IV UFH stratified by patient population and LMWH dosing.
Outcome
All VTE Patients
Patients with PE
LMWH q.d vs. UFH
LMWH b.i.d vs. UFH
Studies
N
RR
(95% CI)
Studies
N
RR
(95% CI)
Studies
N
RR
(95% CI)
Studies
N
RR
(95% CI)
Major Bleeding
Simonneau 93
Simonneau 97
Decousus 98
1146
0.87
(0.46-1.68)
Simonneau 97
612
0.76
(0.27-2.16)
Simonneau 97
612
0.76
(0.27-2.16)
Simonneau 93
Decousus 98
534
0.96
(0.42-2.20)
Mortality
Simonneau 93
Simonneau 97
Decousus 98
Merli 01
Ninet 91
Meyer 95
2272
0.87
(0.58-1.32)
Simonneau 97
Meyer 95
672
0.88
(0.43-1.82)
Simonneau 97
Merli 01
1200
0.99
(0.56-1.76)
Simonneau 93
Decousus 98
Merli 01
Ninet 91
Meyer 95
1362
0.80
(0.47-1.35)
All VTE
Simonneau 97
Decousus 98
Merli 01
1912
0.87
(0.54-1.40)
Simonneau 97
612
0.84
(0.26-2.74)
Simonneau 97
Merli 01
1200
0.99
(0.52-1.88)
Decousus 98
Merli 01
1002
0.79
(0.44-1.41)
Conflict of Interest:
None declared