Should vitamin K antagonist therapy be started simultaneously with parenteral anticoagulation

For patients with an acute episode of venous thromboembolism (VTE), the optimal starting time of long-term therapy with vitamin K antagonists (VKA) and how much overlap should occur with heparin are unclear and the current guidelines and practice are not based on high-quality data. The objective of this study was to perform a meta-analysis on the evidence comparing early versus late initiation of VKA on the effectiveness and safety of anticoagulation. We searched for randomized controlled trials in Medline, EMBASE, Cochrane CENTRAL, IPA and ClinicalTrials.gov. Studies were included if they compared early initiation of VKA (within approximately 24 h) and late initiation (>4 days) of the onset of heparin therapy. Data were pooled using the Review Manager 5 software and the quality of evidence was appraised with Grading of Recommendations, Assessment, Development and Evaluation profiler. Five studies were included in the review, with a total of 840 patients. Meta-analysis of recurrence of VTE, death and major bleeding revealed no significant differences between the two treatment regimens. Minor bleeding [RR 0.65, 95% confidence interval (CI) 0.43-0.98] and hospital stay (mean difference 3.92 days, 95% CI -4.57 to -3.28) were reduced in the early VKA group (P < 0.05). The quality of evidence for each outcome except hospital stay was low. Results from this meta-analysis favour the early start of VKA (within 24 h of the initiation of heparin) based on minor bleeding and resource utilization. However, these results should be interpreted with caution, as the quality and quantity of evidence is limited.