Objective: To discuss the chemistry, pharmacology, and pharmacokinetics of dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative clinical trial data evaluating the efficacy and safety of dalteparin and unfractionated heparin (UH) for the prophylaxis and treatment of venous thromboembolism.
Data sources: A MEDLINE search identified pertinent English-language publications on dalteparin and venous thromboembolism. Key search terms were dalteparin, Fragmin, LMWH, and venous thromboembolism. The search was supplemented by review articles, articles obtained from the bibliographies of the review articles, and the dalteparin approval database.
Study selection: The most pertinent studies describing the pharmacology and pharmacokinetics of dalteparin in humans were selected; all abstracts and clinical evaluating the use of dalteparin for antithrombotic therapy were reviewed. Review articles by authors of international reputation were selected.
Data extraction: Pertinent information from the review articles on the pharmacology of LMWHs and UH was summarized. Clinical trial data were extracted for study design, patient demographics, therapeutic regimens, methods of evaluation, and outcomes.
Data synthesis: Dalteparin is an LMWH indicated for patients undergoing abdominal surgery who are considered to be at risk for deep-vein thrombosis (DVT), which may lead to pulmonary embolism (PE). In this population, numerous clinical trials have demonstrated comparable efficacy between dalteparin and fixed-dose UH for DVT prophylaxis. Dalteparin has a predictable dose response and can be administered as a standard single daily subcutaneous dose for all patients. In therapeutic doses, dalteparin does not alter coagulation tests and therefore does not require routine laboratory monitoring, in contrast with adjusted-dose UH. Bleeding risks with dalteparin are comparable with and possibly less than those associated with UH. Preliminary studies suggest that dalteparin may be effective for other indications, including DVT prophylaxis for hip replacement surgery and the treatment of DVT and PE. Comparative cost-effectiveness data are not yet available.
Conclusions: Dalteparin is the second LMWH to receive approval by the Food and Drug Administration. Dalteparin is indicated for prophylaxis against DVT in patients undergoing abdominal surgery. Clinical studies have shown that single daily doses of dalteparin provide a safe and effective alternative to fixed-dose UH therapy. Additional studies are needed to determine the cost-effectiveness of dalteparin compared with UH and other LMWHs.