Once-daily vs. twice-daily dosing of enoxaparin for the management of venous thromboembolism: A systematic review and meta-analysis

The present study aimed to determine whether there is any difference in the efficacy and safety of once-daily vs. twice-daily enoxaparin when used for the initial treatment of venous thromboembolism (VTE). The PubMed, Embase, Cochrane Central Register of Controlled Trials, Science Direct and Google Scholar databases were searched for studies comparing once-daily and twice-daily enoxaparin for the initial treatment of VTE added from inception up to 1st October 2019. Studies utilizing any other low-molecular-weight heparin and using enoxaparin for VTE prophylaxis were excluded. A total of 6 studies were included in the systematic review and 5 in the meta-analysis. Only one study was a randomized controlled trial (RCT). Pooled analysis of 460 patients receiving once-daily enoxaparin and 464 patients receiving twice-daily enoxaparin indicated no significant difference between the two dosing regimens regarding VTE recurrence [odds ratio (OR)=1.48, 95%CI: 0.75-2.89, P=0.26; I(2)=0%]. No significant difference in major hemorrhagic complications was noted (OR=1.21, 95%CI: 0.52-2.81, P=0.66; I(2)=0%). Sub-group analysis based on study type and use of enoxaparin for bridging therapy did not change the overall results. In cancer patients, no statistically significant difference in the recurrence of VTE was obtained between once-daily and twice-daily enoxaparin, but the confidence intervals were wide with a tendency to favor twice-daily dosing (OR=2.28, 95%CI: 0.91-5.75, P=0.08; I(2)=0%). The overall quality of the studies was determined to be average. To conclude, while the present results suggested no significant difference in efficacy and safety of once-daily vs. twice-daily enoxaparin when used for the initial treatment of VTE, the quality of the evidence may not have been sufficiently high to support the conclusions with confidence. Further high-quality and adequately powered RCTs are required to corroborate the present results.