More Bleeding With Bridge Therapy During Warfarin Interruption

Veronica Hackethal, MD

May 29, 2015

Bridge therapy during warfarin interruption for invasive procedures in patients with a history of venous thromboembolism (VTE) may increase the risk of bleeding, according to a study published online May 26 in JAMA Internal Medicine.

"The use of a bridge agent among patients receiving long-term anticoagulation therapy for a history of VTE was associated with a 17-fold higher risk of bleeding without a significant difference in the rate of recurrent VTE," write Nathan Clark, PharmD, from the Department of Pharmacy, Kaiser Permanente Colorado, and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, and colleagues.

The researchers suggest bridge therapy is "likely unnecessary" for most patients with a history of VTE.

Patients who are receiving warfarin because of past VTE often pose treatment dilemmas when they need invasive procedures. The problem concerns balancing the risk for recurrent VTE with the risk for procedure-related bleeding. Patients at moderate or high risk for recurrent VTE will need to stop taking warfarin for several days before the procedure, increasing the risk for VTE. VTE risk also increases in the postoperative period. High-risk patients can take periprocedural bridging therapy with short-acting, low-molecular-weight heparin, which can reduce the risk for VTE. Real-world risk estimates for VTE and bleeding in such patients, however, are sparse, and guidelines provide only weak, indirect evidence.

The new study addressed this problem by doing a risk–benefit analysis of bleeding and VTE during bridge therapy in real-world settings.

The researchers conducted the retrospective cohort study at Kaiser Permanente in Colorado and included patients who had warfarin interruptions for invasive diagnostic or surgical procedures between January 2006 and March 2012. The investigators searched Kaiser Permanente administrative databases and did manual searches to identify patients, then collected information on exposure to bridge therapy and outcomes between June 2005 and April 2012. They used guidelines from the American College of Chest Physicians to stratify patients according to high, moderate, or low risk for VTE.

The analysis included 1178 patients who received 1812 procedures (555 during bridge therapy, 1257 without bridge therapy).

Of the 1812 procedures, 1431 (79.0%) were in low-risk, 324 (17.9%) were in moderate-risk, and 57 (3.1%) were in high-risk patients.

Bridge therapy was administered to 410 of 1431 (28.7%) low-risk patients, 109 of 324 (33.6%) moderate-risk patients, and 36 of 57 (63.2%) high-risk patients.

Fifteen clinically relevant bleeding events occurred within 30 days of the procedure (2.7%; 95% confidence interval [CI], 1.5% - 4.4%) in patients who received bridge therapy compared with two events (0.2%; 95% CI, 0.02% - 0.6%) in the nonbridge therapy group (hazard ratio, 17.2; 95% CI, 3.9 - 75.1). In the bridge therapy group, nine (52.9%) of the bleeding events were procedure-related and five (33.3%) were linked to bridge therapy.

Three patients (0.2%) who did not receive bridge therapy experienced recurrent VTE: two of the low-risk patients, one of the intermediate-risk patients, and none of the high-risk patients.

The bridging therapy vs nonbridging therapy groups had no significant rates of recurrent VTE (0 vs 3; P = .56).

Limitations include those inherent in the use of administrative data, such as omitted or misclassified data. Because of low event rates, the authors could not adjust the results for potential confounding.

"Our results...highlight the need for a risk categorization scheme that identifies patients at highest risk for recurrent VTE who may benefit from bridge therapy," the authors conclude.

In an invited commentary, Daniel Brotman, MD, and Michael Streiff, MD, both from the School of Medicine, Johns Hopkins University, Baltimore, Maryland, agreed about the need for better categorization and that most bridging therapy may be unnecessary.

"[W]e support the authors' contention that the majority — indeed the vast majority — of patients receiving anticoagulants for a history of VTE should not be given therapeutic-dose bridge therapy, and that revision of the [American College of Chest Physicians] risk-stratification recommendations is warranted," they write.

"There are undoubtedly some patients at such high risk for recurrent VTE that bridge therapy is a necessary evil.... However, for the vast majority of patients receiving oral anticoagulants for VTE, it is probably safer to simply allow the oral anticoagulant to wash out before the procedure and, if indicated based on the type of surgery, to use routine prophylactic-dose anticoagulation therapy afterward. Parenteral anticoagulants are inherently high-risk medications that should be used with great caution, particularly in the postoperative setting: first, do no harm."

One coauthor reports consulting for Boehringer-Ingelheim, Astra-Zeneca, Pfizer, and Sanofi. Dr Streiff reports research funding from Bristol-Myers Squibb and Portola, and consulting for Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Janssen HealthCare, Pfizer, and Sanofi. The other authors and Dr Brotman have disclosed no relevant financial relationships.

JAMA Intern Med. Published online May 26, 2015. Article abstract, Commentary extract

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