Periprocedural Heparin Bridging in Patients Receiving Vitamin K Antagonists: Systematic Review and Meta-Analysis of Bleeding and Thromboembolic Rates

Study Questions:

What is the safety and efficacy of periprocedural bridging anticoagulation in patients receiving long-term vitamin K antagonists?


The authors performed a systematic review and meta-analysis using the Meta-Analysis Of Observational Studies In Epidemiology (MOOSE) guidelines for studies published from January 1, 2001, until July 31, 2010, which included patients who received heparin bridging during interruption of vitamin K antagonists for elective procedures. All studies were reviewed by two of the authors, and included if the studies evaluated patients over age 18, receiving periprocedural bridging with low molecular weight heparin (LMWH), and reported thromboembolic and bleeding events. Final review included 34 studies, one of which was a randomized trial. Data were pooled by use of the Mantel-Haenszel method, and a random-effects model was performed with generation of odds ratios.


The authors reported that thromboembolic events occurred in 73 of 7,118 bridge patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0-3.4), and in 32 of 5,169 bridge stations (pooled incidence, 0.6%; 95% CI, 0.0-1.2). In eight studies that compared bridged and nonbridged patients, there was no statistically significant difference in risk of thromboembolic events (odds ratio [OR], 0.80; 95% CI, 0.42-1.54). In 13 studies, there was an increased risk of bleeding (OR, 5.40; 95% CI, 3.00-9.74), and in five studies looking at major bleeding, there was also an increased incidence (OR, 3.60; 95% CI, 1.52-8.50), comparing bridged and nonbridged patients. Full-dose LMWH versus prophylactic dose was not associated with any difference in thromboembolic events (OR, 0.30; 95% CI, 0.04-2.09), but was associated with an increased risk of overall bleeding (OR, 2.28; 95% CI, 1.27-4.08). The quality of studies was deemed to be poor, with heterogeneity for some of the analyses.


The authors concluded that vitamin K antagonist-treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding, and at similar risk of thromboembolic events compared to nonbridged patients. The authors further opined that randomized trials are needed to define the role of periprocedural heparin bridging.


Many of us face the clinical dilemma of how to manage chronic warfarin therapy when patients require invasive procedures or testing. The data from this study provide a summary of the existing literature, which is strikingly lacking in randomized clinical trials. The data from this meta-analysis suggest that there is only a nonsignificant trend toward fewer thromboembolic events in patients on chronic warfarin therapy who are bridged with heparin at the time of an invasive procedure, but that bridging therapy is associated with a significant increase in bleeding events. These data would support what is the current common practice—selective bridging only. This leaves the clinician with the basic question still unanswered: Which patients on chronic warfarin therapy would benefit from periprocedural bridging with heparin? Clearly, randomized trials are badly needed.

Clinical Topics: Anticoagulation Management

Keywords: Vitamin K, Odds Ratio, Blood Coagulation, Risk, Warfarin, Heparin, Cardiovascular Diseases, Fibrinolytic Agents, Confidence Intervals, Hemorrhage

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