Bridge therapy increases bleeding rates after invasive procedures

Last Updated: 2015-05-27

By Will Boggs MD

NEW YORK (Reuters Health) - Bridge therapy with heparin during warfarin interruption for invasive procedures is associated with increased bleeding rates in the 30 days that follow, according to a retrospective study.

Heparin is often used during warfarin interruption for patients at high risk of recurrent venous thromboembolism (VTE), but risk estimates of bleeding and VTE associated with this bridge therapy are lacking in real-world patients with VTE.

Dr. Thomas Delate from Kaiser Permanente Colorado (KPCO) in Aurora and colleagues reviewed data from KPCO's electronic patient tracking tool and electronic medical records to compare real-world rates of clinically relevant bleeding and recurrent VTE among patients receiving warfarin for a prior VTE in whom treatment was interrupted for invasive procedures.

Out of 1812 procedures, bridge therapy was used in 555.

Bridge therapy was used for 28.7% of low-risk patients, 33.6% of moderate-risk patients, and 63.2% of high-risk patients, according to the May 26th JAMA Internal Medicine online report.

The 30-day rate of clinically relevant bleeding was much higher in the bridge therapy group than in the non-bridge therapy group (15 events, 2.7%, vs 2 events, 0.2%; hazard ratio, 17.2).

Clinically relevant bleeding rates did not differ significantly between those receiving a therapeutic or a prophylactic dose of a bridge anticoagulant. More than half the bleeding events were procedure complications, and one-third were related directly to bridging agent injections.

Major bleeding was also significantly more common with vs without bridge therapy (2.2% vs 0.2%; P<0.001).

Recurrent VTE rates did not differ between the bridge and non-bridge therapy groups, and there were no deaths in either group.

"Thus, the risk of bleeding associated with bridge therapy appeared to outweigh the potential benefits in our study population," the researchers conclude. "Our results highlight the need for further research to identify patient- or procedure-related characteristics that predict a high risk of VTE recurrence during interruption of warfarin therapy."

Dr. Daniel J. Brotman, from The Johns Hopkins University in Baltimore, Maryland, who coauthored a commentary on the report, told Reuters Health by email, "I would put patients in a high-risk group only if they (1) have had recurrent thromboses, particularly in the setting of brief anticoagulation cessation, (2) thrombosis in the prior 4-6 weeks, and (3) some instances of catastrophic thrombosis from hypercoagulable conditions (e.g., massive pulmonary embolism or fulminant liver failure from Budd-Chiari syndrome in the context of antiphospholipid antibodies or JAK-2 mutations). Other patients should be generally categorized as low-to-intermediate risk. In these patients, bridging anticoagulation should be restricted to prophylactic dose anticoagulants, rather than full (therapeutic) doses."

"Of course there may be exceptions to this approach, but the vast majority of patients with prior VTE should not receive bridging anticoagulation with full-dose heparin products, particularly post-procedurally," Dr. Brotman said.

"Before a thrombus stabilizes (in the first few weeks of treatment), there is a very high rate of embolization when anticoagulation is stopped, but beyond that time period, the risk is appreciably lower," Dr. Brotman continued. "Patients who develop recurrent thromboses promptly upon anticoagulation cessation constitute a very challenging, but fortunately small, population. These patients are better identified based on their prior history than based on laboratory tests, although many of them will have laboratory detected thrombophilias (particularly antiphospholipid antibodies)."

Dr. Ramez Nairooz from the University of Arkansas for Medical Sciences in Little Rock recently reported on major bleeding rates with and without bridge therapy in patients with atrial fibrillation. He told Reuters Health by email, "These results are important to the medical community; however they are not surprising. Patients at low risk of recurrent VTE mostly should not be bridged for most procedures and this study confirms that."

"This study contains a small number of high risk patients and no conclusive evidence can be withdrawn from that but expert opinion and conventional wisdom goes with bridging high risk patients," Dr. Nairooz said.

Dr. Nairooz cautioned, "The study lacks information on the anticoagulant used for bridging - unfractionated heparin, fondaparinux or enoxaparin. These anticoagulants are known to have different effects on bleeding outcomes." He also pointed out, "This study lacks analysis based on procedural risk which should be taken in account when deciding on peri-procedural anticoagulant management."

Dr. Delate did not respond to a request for comments.

SOURCE: http://bit.ly/1SCLrxH

JAMA Intern Med 2015.