What are the benefits and harms of bridge therapy for patients with venous thromboembolism who have interruption of warfarin during the periprocedural setting?
Using bridge therapy during the warfarin interruption period for patients with venous thromboembolism (VTE) is associated with increased bleeding. Moreover, withholding bridge therapy is not associated with increased risk of recurrent VTE. The risk-benefit ratio from this study suggests that bridge therapy may be unnecessary for VTE patients, especially those already at low risk for recurrence. (LOE = 2b)(www.essentialevidenceplus.com)
Clark NP, Witt DM, Davies LE, et al. Bleeding, recurrent venous thromboembolism and mortality risks during warfarin interruption for invasive procedures. JAMA Intern Med 2015;175(7):1163-1168.
Study design: Cohort (retrospective)
Funding source: Foundation
Setting: Outpatient (any)
Patients who use warfarin therapy for the secondary prevention of VTE and who had interruption of that therapy for a procedure were included in this study. Patients were stratified by their underlying risk for recurrent VTE as determined by the timing of their previous VTE and the presence and severity of thrombophilia. For example, those with an acute VTE within the past 3 months or with severe thrombophilia were considered to be at high risk for recurrence while those with VTE more than 1 year ago were considered to be at low risk. Investigators used a pharmacy database and electronic medical records to identify those patients who received bridge therapy with heparin products during the warfarin interruption period. The overall cohort had a mean age of 66 years and the most common reason for the interruption was a gastrointestinal endoscopic procedure. Almost 80% of the cohort fit the low-risk category for recurrence of VTE. Bridge therapy was used in one-third of the overall cohort but the proportion increased with risk categories (29% in the low-risk group, 34% in the moderate-risk group, 63% in the high-risk group). The primary outcome of 30-day clinically relevant bleeding was higher in the bridge therapy group than in the no-bridge therapy group (2.7% vs 0.2%, hazard ratio 17.2, 95% CI 3.9-75.1). However, recurrent VTE did not significantly differ between the bridge and no-bridge groups, even when analyzing across individual risk categories. Of the patients who did not receive bridge therapy, 0 of the 21 high-risk patients and only 1 of the 215 moderate-risk patients had recurrent VTE.
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Does bridging anticoagulation during a procedure improve or worsen patient-oriented outcomes?
This study provides more evidence that bridging in patients with nonvalvular atrial fibrillation not only does not improve outcomes, it is actually associated with a higher risk of both bleeding complications and cardiovascular events. (LOE = 2b)(www.essentialevidenceplus.com)
Steinberg BA, Peterson ED, Kim S, et al, for the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation Investigators and Patients. Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Circulation 2015;131(5):488-494.
Study design: Cohort (prospective)
Funding source: Industry + govt
Bridging anticoagulation substitutes an anticoagulant that is slower to reverse (such as warfarin) with one that is easily reversed in case of emergency (heparin) in patients undergoing a surgical procedure. But does all that hassle really improve outcomes? A recent randomized trial in patients undergoing placement of a pacemaker found that bridging anticoagulation led to worse outcomes (http://www.essentialevidenceplus.com/content/poem/150701). In the current study, researchers used a large registry that follows patients who are anticoagulated for nonvalvular atrial fibrillation (ORBIT-AF). The registry has data on 10,132 patients; after excluding those not using an oral anticoagulant, there were 7372 in the study population who underwent 2803 interruptions. The most common indications were for noncardiac surgery (27%), endoscopy (18%), and other procedures (25%). Approximately three fourths did not use bridging anticoagulation, while the remainder did. The CHA2DS2-VASc score was similar between groups. Bridging was more often used for patients undergoing cardiac procedures and less often for those undergoing dental procedures or endoscopy. Although the patients who bridged were generally similar to those who did not in terms of demographics, they did have a higher likelihood of previous cerebrovascular event (22% vs 15%, P < .001), heart failure, significant valve disease, coronary artery disease, and prior mechanical valve replacement. In the adjusted analysis, the 30-day likelihood of a cardiovascular event was higher in the bridged patients (4.6% vs 2.5%; adjusted odds ratio [aOR] 1.6; 95% CI 0.95 - 2.8; number needed to treat to harm [NNTH] = 47) and bleeding events (5.0% vs 1.3%; aOR 3.8; 2.1 - 7.1; NNTH = 27). There was no difference in the risk of stroke or thrombotic events.
Mark H. Ebell, MD, MS
University of Georgia
Does bridging anticoagulation during invasive procedures improve outcomes in patients with atrial fibrillation who take warfarin?
Bridging anticoagulation worsens outcomes for patients with atrial fibrillation who undergo an elective invasive procedure, resulting in more episodes of major bleeding and no difference in the rate of stroke or venous thromboembolism. Most of the patients in the study had a CHADS2 score of 1 (23%), 2 (40%), 3 (24%), or 4 (10%). The patients were largely undergoing minor surgical procedures with low bleeding risk and patients at very high risk for thromboembolism or stroke were not represented in this study. (LOE = 1b)(www.essentialevidenceplus.com)
Douketis JD, Spyropoulos AC, Kaatz S, et al, for the BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015;373(9):823-833.
Study design: Randomized controlled trial (double-blinded)
Funding source: Government
Setting: Inpatient (any location)
The evidence for bridging anticoagulation is looking increasingly questionable, with a recent registry-based study finding worse outcomes with bridging (http://www.essentialevidenceplus.com/content/poem/170602). This study provides the best evidence to date. A total of 1884 adults with chronic atrial fibrillation and at least one CHADS2 risk factor were randomized to bridging anticoagulation with dalteparin or to placebo. Patients with a mechanical heart valve, recent stroke or embolism, impaired renal function, or thrombocytepenia were excluded, as were patients undergoing cardiac, intracranial, or intraspinal surgery. All participants had received warfarin for at least 3 months and had an INR between 2.0 and 3.0. The protocol for bridging was as follows: (1) stop warfarin 5 days before the procedure, (2) start dalteparin or placebo 3 days before the procedure, (3) stop the study drug 1 day before the procedure, (4) restart warfarin 12 hours to 36 hours after the procedure, and (5) restart the study drug 12 hours to 72 hours after the procedure (based on bleeding risk) and continue it until the INR is therapeutic. The mean age of patients was 72 years, and the mean CHADS2 score was 2.3 (range = 1 - 6). Basically, the bridging group had their time without anticoagulation minimized, while the placebo group was without anticoagulation for approximately 10 days (2 to 3 days before the procedure and a mean of 8 days after). Most of the procedures were classified as low bleeding risk. At 30 days, the risk of arterial thromboembolism did not differ between groups (2 strokes and 2 transient ischemic attacks in the placebo group, and 3 strokes in the bridging group). The risk of major bleeding was significantly higher in the bridging group (3.2% vs 1.3%; P = .01; number needed to treat to harm [NNTH] = 53). There was no difference between groups in the likelihood of death, myocardial infarction, deep vein thrombosis, or pulmonary embolism. Minor bleeding was also more common in the bridging group (20.9% vs 12.0%; P < .001; NNTH = 11).
Is routine computed tomography of the abdomen and pelvis in patients with an initial unprovoked episode of venous thromboembolism helpful?
There is no advantage to adding computed tomography (CT) of the abdomen and pelvis to a basic screening protocol for occult malignancy in patients with unprovoked venous thromboembolism. (LOE = 1b)(www.essentialevidenceplus.com)
Carier M, Lazo-Langner A, Shivakumar S, et al. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med 2015; 373: 697-704.
Study design: Randomized controlled trial (single-blinded)
Setting: Outpatient (specialty)
Patients with an unprovoked episode of deep vein thrombosis (DVT) or pulmonary embolism (PE) are at increased risk of occult malignancy. However, the best approach to evaluate patients for cancer is unclear. In this trial, adults with a first diagnosis of an episode of DVT or PE at 1 of 9 Canadian centers were randomized to receive either a basic evaluation for occult malignancy (history and physical, basic blood tests, chest x-ray, mammogram for women older than 50 years, Pap test for sexually active women aged 18 to 70 years, and prostate cancer screening for men older than 40 years) or the same evaluation plus a comprehensive CT of the abdomen and pelvis. Patients with impaired renal function or allergy to contrast media, and those who could not easily comply with a CT scan, were excluded. A total of 3186 patients were evaluated for eligibility, 862 were randomized, and 854 were included in the intention-to-treat analysis. The mean age of the included patients was 53 years, 67% had a DVT, 33% PE, and 12% had both. Overall, 33 patients (3.9%) had a new diagnosis of cancer during the first year of follow-up: 14 in the basic screening group, and 19 in the group that also received a CT scan. The mean time to a new cancer diagnosis was 4.2 months for the patients who received basic screening, and 4 months for those who also received CT.
POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).
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Top POEMs of 2015 Consistent with the Principles of the Choosing Wisely Campaign
Anticoagulant Therapy/Venous Thromboembolism