??bridge therapy for patients on warfarin and invasive procedures

A pretty common primary care conundrum is what to do with patients who are on warfarin but have impending surgery: stop the warfarin and hope they don't get a pulmonary embolus, or do bridge therapy (there are several different ways to do the bridging: for those at high risk of venous thromboembolism --VTE, full-dose bridging is often done: stopping the warfarin 5 days prior to surgery, starting low molecular-weight heparin soon thereafter, stopping that for the surgery, and then restarting the heparin soon after the surgery (can be 1 day in those at low risk of post-op bleeding, longer if at higher risk); can do prophylactic low-dose heparin post-op; or can do intermediate (about 1/2 full-dose) for those with higher risk (eg VTE within the past month). Warfarin is resumed 12-24 hours post-op and usually takes 4-6 days to achieve target anticoagulation. A recent study in JAMA Internal Medicine looked at the outcome of 1178 patients in a retrospective cohort study in a large HMO (Kaiser Permanente Colorado) from 2006-2012 who were on warfarin for a VTE and had surgery with or without bridging (see dvt bridge therapy surgery jamaintmed 2015 in dropbox, or doi:10.1001/jamainternmed.2015.1843​). They looked at the 30-day occurrence of clinically relevant bleeding, recurrent VTE, and all-cause mortality. details:

--1178 patients: mean age 66, 46% men, 56% on warfarin for deep venous thrombosis (dvt) and 44% for pulmonary embolism, 10 % with laboratory-confirmed thrombophilia (Protein S or C deficiency, antithrombin deficiency, antiphospholipid antibody syndrome, factor V Leiden, prothrombin 20210 mutation, increased factor VIII).

--per the American College of Chest Physicians guidelines (AT9 guidelines, see dvt guidelines periop management on warfarin chest 2012 in dropbox, or CHEST 2012; 141(2)(Suppl):e326S–e350S), 79% of patients were considered low risk for VTE recurrence at the time of surgery, 18% moderate and 3% high risk (see below for risk stratification), and bridge therapy was done, respectively, in 29%, 34%. and 63% of the surgeries. 73% used therapeutic doses in the bridge therapy and 28% used prophylactic doses

--procedures done: 37% GI endoscopies, 14% orthopedic, 10% spinal/intracranial, 9% abdominal. Of the surgeries, bridge therapy was performed more often for orthopedic and nonmajor abdominal or thoracic procedures

--results:

      --clinically relevant bleeding within 30 days occurred in 15 patients (2.7%) in the bridge therapy group , but only in 2 patients (0.2%) without bridge therapy [(HR=17.2 (3.9-75.1)]

            ​--high VTE risk group--5.6% with bridge therapy, 4.8% without. nonsignificant

            ​--moderate VTE risk group--4.6% with bridge therapy, 0% without. p=0.004

            ​--low VTE risk group--2.0% with bridge therapy, 0.1% without. p<0.001

            ​--no significant difference in bleeding between those receiving therapeutic vs prophylactic doses in the bridge therapy

​      --no significant difference between groups in the rate of recurrent VTE in the bridge vs non-bridge groups (0 vs 3 patients, p=0.53)

            ​--high VTE risk group--0% with bridge therapy, 0% without. nonsignificant

            ​--moderate VTE risk group--0% with bridge therapy, 0.5% without. nonsignificant

            ​--low VTE risk group--0% with bridge therapy, 0.2% without. nonsignificant

       --no deaths in either group

general comments:

--it makes sense to stratify patients by surgical risk of bleeding: low risk (eg dental work)-continue with warfarin and therapeutic INR; moderate to high risk- stop the warfarin 5 days before the surgery (per AT9)

--the rationale for bridge therapy is two-fold: to decrease the amount of time the patient is not anticoagulated overall (around 7-10 days), but especially to do so in the high risk post-op period for VTE, since surgery leads to a more hypercoagulable state.

--the 2012 AT9 guidelines classifies the risk of recurrent VTEs in the post-op period as high (>10%/yr --eg, VTE within 3 months, severe thrombophilia), moderate (5-10%/yr --eg, VTE in past 3-12 months, non-severe thrombophilia such as heterozygous for factor V  Leiden or prothrombin gene mutation) and low (<5%/yr -- eg, VTE>12 months previous and no other risk factors). This risk stratification is based on the annual risk of recurrent VTE in patients with mechanical heart valve, chronic atrial fibrillation or VTE who were either on no anticoagulation or less-effective treatment (eg aspirin).  ie, there is only indirect evidence to establish these risk categories for those with VTE on therapeutic anticoagulation.

so, this study is large but limited by being retrospective, and only a small % of the patients were high risk. However, it is impressive that bridge therapy made no difference in VTE occurrence in the much larger moderate and low risk groups, though there was a much higher risk of clinically relevant bleeding. we really need a prospective study, randomizing patients in the different risk categories to bridge therapy or not.  a prospective study could also sort out if there were other risk factors to consider which might favor bridge therapy, including those with a recent VTE (the risk is highest in the first 4 weeks post-VTE, 0.3-1.3%/day, decreasing to 0.03-0.2%/day over the next 4-12 weeks), or in those with several previous recurrences. also, we should note that this study did not include patients anticoagulated for atrial fibrillation or other indications (and it would be great to have good data on that... currently,  AT9 considers those in atrial fib with CHADS₂ score of 0-2 as low risk, 3-4 as moderate, and 5-6 as high risk. also high risk is if there is rheumatic heart disease or stroke/TIA within the past 3 months). but at least the current study gives some pretty strong support for withholding bridge therapy in those who are at least a few months out from their VTE event and who are in low or moderate VTE risk.