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A Systematic Review and Meta-analysis

Elie A. Akl, MD, MPH; Irene Terrenato, PhD; Maddalena Barba, MD; Francesca Sperati, PhD; Elena V. Sempos, MD, MPH; Paola Muti, MD, MSc; Deborah J. Cook, MD, MSc; Holger J. Schünemann, MD, PhD

Arch Intern Med. 2008;168(12):1261-1269.

Background  The relative benefits and harms of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) are required for judgments regarding the appropriate perioperative thromboprophylaxis in patients with cancer. We systematically reviewed the literature to quantify these effects.

Methods  The comprehensive searches included (1) an electronic search of MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL (The Cochrane Central Register of Controlled Trials); (2) a hand search of relevant conference proceedings; (3) a reference check of included trials; and (4) use of the PubMed "Related Articles" feature. Outcomes of interest included mortality, deep venous thrombosis, pulmonary embolism, bleeding complications, and thrombocytopenia.

Results  Of 3986 identified citations, we included 14 randomized clinical trials in the meta-analysis (all using preoperative prophylactic anticoagulation). The overall methodological quality was moderate. The meta-analysis showed no differences in mortality in patients receiving LMWH compared with UFH (relative risk [RR], 0.89; 95% confidence interval [CI], 0.61-1.28) or in clinically suspected deep venous thrombosis (RR, 0.73; 95% CI, 0.23-2.28). In a post hoc analysis including all studies assessing deep venous thrombosis, irrespective of the diagnostic strategy used, LMWH was superior to UFH (RR, 0.72; 95% CI, 0.55-0.94). There were no differences in rates of pulmonary embolism (RR, 0.60; 95% CI, 0.22-1.64), minor bleeding (RR, 0.88; 95% CI, 0.47-1.66), or major bleeding (RR, 0.95; 95% CI, 0.51-1.77).

Conclusions  We found no differences in mortality in patients with cancer receiving perioperative thromboprophylaxis with LMWH vs UFH. Further trials are needed to more carefully evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population.

Author Affiliations: Department of Medicine, State University of New York at Buffalo (Dr Akl); Department of Epidemiology, Italian National Cancer Institute Regina Elena, Rome (Drs Terrenato, Barba, Sperati, Muti, and Schünemann); Department of Veterans Affairs, Perry Point, Maryland (Dr Sempos); and Department of Medicine (Dr Cook) and CLARITY Research Group, Department of Clinical Epidemiology and Biostatistics (Drs Cook and Schünemann), McMaster University, Hamilton, Ontario, Canada.

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