Comparison of the efficacy and safety of low molecular weight heparins for venous thromboembolism prophylaxis in medically ill patients

Abstract

Objective:

To conduct a systematic review and mixed-treatment comparison (MTC) meta-analysis to compare the efficacy and safety of low molecular weight heparins (LMWHs) for venous thromboembolism (VTE) prophylaxis in hospitalized medically ill patients. As a secondary objective we compared all therapies within the network to each other.

Methods:

We conducted a systematic literature search for randomized trials that evaluated pharmacologic VTE prophylaxis in hospitalized medically ill patients. We conducted a traditional meta-analysis for all pairwise comparisons using a random effects model, reporting relative risks (RRs) and 95% confidence intervals for each outcome. To determine the relative efficacy and safety of included therapies we conducted a MTC meta-analysis using a Bayesian framework, reporting odds ratios (OR) and 95% credible intervals.

Results:

Twenty trials met inclusion criteria. Enoxaparin, dalteparin, nadroparin and certoparin were the LMWHs evaluated although none in direct comparative trials. Upon MTC, the relative efficacy of all LMWHs was similar in preventing mortality and VTE as well as in the odds of major and minor bleeding. Dalteparin was not included in the network to evaluate deep vein thrombosis (DVT) and pulmonary embolism (PE) due to lack of reported data and the remaining LMWHs were found to be similar in relative efficacy in preventing these outcomes.

Limitations:

Traditional meta-analysis was not possible for many drug comparisons made within the MTC. Heterogeneity was observed in several of the traditional meta-analyses although this may be an inherent limitation of the studied population. Overall rarity of events contributed to imprecise estimates demonstrated by the wide confidence intervals.

Conclusions:

Enoxaparin, dalteparin, nadroparin and certoparin are similar in relative efficacy for the prevention of mortality and VTE and in the odds of major or minor bleeding while enoxaparin, nadroparin and certoparin are similar in relative efficacy for the prevention of PE and DVT in hospitalized medical patients.

Keywords::

• Low molecular weight heparin
• Prophylaxis
• Venous thromboembolism

Transparency

Declaration of funding

The authors received no payment in preparation of this manuscript.

Declaration of financial/other relationships

C.D., R.K., and D.M.S. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.