Overuse of Bridging Anticoagulation for Patients With Venous Thromboembolism: First, Do No Harm.

Abstract

Patients receiving anticoagulation for venous thromboembolism (VTE) have varying risks of recurrence on cessation of the therapy. Time from the most recent thrombotic event is perhaps the most important determinant of short-term VTE recurrence because patients who stop anticoagulation therapybefore the stabilizationof an active thrombus are particularly prone to propagation and embolization. If use of anticoagulation is stopped during the first 4 weeks of treatment, the risk of recurrent VTE is 0.3% to 1.3% per day, dropping to 0.03% to 0.2% per day over the next 4 to 12 weeks.1 After 3months, many patients can safely discontinue anticoagulation therapy, particularly if the thrombotic event occurred in the setting of a reversible precipitant. The importanceofdetermining the time frameof themost recent thrombotic episode is reflected in the currentAmerican College of Chest Physicians (ACCP) guidelines,2 which suggest stratifying patients who are receiving anticoagulation therapy for a history of VTE are at high risk for recurrence during anticoagulant cessation if the thrombosis occurredwithin the previous 3 months, intermediate risk if the thrombosis occurred within the past 3 to 12 months, and low risk if the event occurredmorethan12monthsearlier.Hypercoagulabilitycanalso tippatients intohigher-risk categories: theACCPguidelines include as high-risk thrombophilias homozygous prothrombotic mutations; protein C, S, or antithrombin deficiency; antiphospholipid antibodies; or multiple thrombophilic traits. Intermediate-riskthrombophilias includecancer, recurrentVTE, andsingleprothromboticmutations.Thisparadigmismoreconservative thanother suggested schemas that donot categorize all patientswithVTE in thepreceding3monthsashigh riskand give lowerpriority to laboratory-based thrombophilias that are not associated with recurrent VTE.1 In recent years, the literature3,4 has highlighted the bleeding risk conferred by use of full-dose anticoagulants following surgicalprocedures,particularlywhenthemedication isstarted in the first 2 to 3 days after surgery. Yet, for patients with prior VTE, the postoperative setting is a particularly high-risk time for recurrence since surgery itself is a potent VTE precipitant. Giventhisclinical landscape, thearticlebyClarkandcolleagues5 in this issue of JAMA Internal Medicine is a welcome addition totheliterature.Leveragingalargeadministrativedatabasefrom an integratedhealth care system, these authors identified 1812 procedures in 1178 patients receiving warfarin for VTE who stoppeditsuse intheperiprocedural setting.Bridgetherapywas identified by the purchase of parenteral anticoagulants by patientsandbyreviewofperiproceduralplansdocumented inanticoagulationclinic records.Bleedingandthromboticeventsoccurring within 30 days of the procedure were adjudicated via manual review of the medical records. Patient risk was stratified in accordance with current ACCP guidelines.2 However, since bridgingwas not standardized, approximately one-third of patients in the lowand intermediate-risk strata received bridgetherapy,andfewerthantwo-thirdsofpatients inthehighrisk stratum received bridge therapy. Consistentwithprior studies,4 2.7%of thepatientswhoreceived bridge therapy developed clinically relevant bleeding compared with only 0.2% of those who did not receive bridge anticoagulationtherapy.More important,only3patients (0.2%) who did not receive bridge therapy developed recurrent VTE. None of the 21 high-risk patients and only 1 of the 215 intermediate-riskpatientswhodidnot receivedbridge therapyhad recurrentVTE.Toputthesefindings instarkterms,bridgetherapy, despite being administered to only one-third of patients overall, ledtoapproximately14incrementalclinicallyrelevantbleeding events,whereas therewereonly 3 thrombotic events in the remaining two-thirds of the cohort who did not receive bridge therapy, with no signal that the current ACCP risk-stratificationschemasuccessfully identifiedpatientsathighenoughrisk for thrombosis to justifybridgetherapy.Althoughthisstudywas not powered to assess mortality (with no deaths in the entire cohort), we know from other studies that approximately 10% ofVTEpatientswhohavemajor bleedingdie,6,7 comparable to the case fatality rate from recurrent VTE.7,8 In contrast to patientswho experience cardioembolism, survivors of recurrent deep vein thrombosis or pulmonary embolism rarely have serious permanent sequelae. The present study is not without its limitations, particularly the lackof discriminationbetween full-dose andprophylactic-dose parenteral anticoagulants used as bridge therapy and the absence of information on the timing of anticoagulation therapy. Nevertheless, it is likely that the imbalance between bleeding and thrombotic events between subgroups would have been even more dramatic had all patients in the bridge therapygroup received full-doseparenteral anticoagulants in the immediatepostoperative setting.As such,we support theauthors’ contention that themajority—indeed thevast majority—of patients receiving anticoagulants for a history of VTE shouldnot be given therapeutic-dosebridge therapy, and that revision of the ACCP risk-stratification recommendations is warranted. There are undoubtedly some patients at such high risk for recurrent VTE that bridge therapy is a necessary evil, such as those with acute VTE in the preceding month and thosewith a prior pattern of brisk VTE recurrence during short-term interruption of anticoagulation therapy. Related article page 1163 Risks DuringWarfarin Interruption for Invasive Procedures Original Investigation Research