A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism - Examining some unanswered questions regarding location of treatment, product type, and dosing frequency

Objectives: To compare the efficacy and safety of unfractionated heparin (U FH) and low-molecular-weight heparins (LMWHs) and to examine current contro versies in the treatment of venous thromboembolism (VTE) (iel setting, prod uct type, and frequency of administration). Methods: Data were abstracted from MEDLINE, HEALTH, previous reviews, perso nal files, clinical experts, and conference abstracts. Randomized controlle d trials of patients diagnosed with acute VTE that compared LMWHs with UFH were included. Independent duplicate assessment was done for methodological quality and data extraction. Data are reported as pooled relative risks (R Rs) and 95% confidence intervals (CIs) comparing LMWHs with UFH as determin ed by the random effects model. Results: Thirteen studies were included. There was no statistically signifi cant difference in risk between UFH and LMWHs for recurrent VTE (RR, 0.85 [ 95% CI, 0.65 - 1.12]), pulmonary) embolism (RR, 1.02 [95% CI, 0.64-1.62]), major bleeding (RR, 0.63 [95% CI, 0.37-1.05]), minor bleeding (RR, 1.18 [95 % CI, 0.87-1.61]), and thrombocytopenia (RR, 0.85 [95% CI, 0.45-1.62]). The re was a statistically significant difference for risk of total mortality ( RR, 0.76 [95% CI, 0.59-0.98]) in favor of LMWHs. Inpatient treatment may re duce the risk of major bleeding vs outpatient therapy. Once-daily therapy i s as safe and effective as twice-daily therapy when compared indirectly. Di fferent products could not be statistically compared, but qualitative analy sis shows that there are no apparent differences in efficacy and safety. Conclusions: Low-molecular-weight heparins are at least as effective as UFH in preventing recurrent VTE. It is unlikely that LMWHs are superior in the treatment of VTE, but they do show a statistically significant decrease in total mortality. No differences were seen in the development of recurrent VTE dependent on treatment setting. There were no apparent differences betw een once-daily and twice-daily therapy or among products. Inpatient therapy may be associated with less major bleeding; therefore, if LMWHs are given in the outpatient setting, patients should be rigorously monitored.