Warfarin Interruption Research Articles

Anticoagulation Strategy in Patients with HeartMate II Undergoing Elective Surgery

Introduction Management of anticoagulation in patients with left ventricular assist devices (LVADs) undergoing elective invasive procedures or surgeries is challenging. We studied the patterns and outcomes of management of anticoagulation in patients with HeartMate II. Methods We prospectively included patients with HeartMate II, followed at our institution, who were scheduled for elective invasive procedures or surgeries, and recorded anticoagulation management. Primary outcome was bleeding or pump thrombosis within 3 months following the procedure. Chi square test was used to calculate statistical significance. Results A total of 29 patients underwent 41 elective procedures. Before procedure, all were taking warfarin. Their mean INR was 2.3±0.9, and mean dose of warfarin was 4.9±2 mg/day. Five patients had more than one procedure. Out of them, 21 had 34 elective invasive procedures or surgeries raging from endoscopy and dental extraction to ileostomy reversal. There was no significant blood loss, with hematocrit 32.1±6.4 and 32.2±6.0 before and after procedure, respectively. INR on the day of the procedure was 1.6±0.4. Bleeding or thrombotic events within three months of the procedure occurred in 5 cases (16.1%). Anticoagulation was continued without interruption in 9 (26.4%) cases, interrupted without bridging in 16 (52.8%), and interrupted with bridging with heparin/low molecular weight heparin in 9 (26.4%) cases. In those who had uninterrupted anticoagulation during the procedure, one patient (11.1%) had oral bleeding requiring hospitalization after teeth extraction. There were no thromboembolic events. In patients with interruption of warfarin but no bridging there were no bleeding complications but there was one pump thrombosis requiring the device exchange (6.3%). Patients who were bridged had 4 bleeding events and no thrombosis (44.4%), p Additionally, 10 patients had procedures in the catheterization laboratory, including right heart catheterization and cardiomems implantation. All of them continued routine anticoagulation with warfarin. Only one patient with history of recurrent gastrointestinal bleeding was admitted for GI bleeding one month after cardiomems implantation. Conclusions In patients with HeartMate II, bridging with low molecular weight heparin results in more bleeding events than continuing anticoagulation without interruption or interrupting warfarin without bridging.

Stroke and transient ischemic attacks related to antiplatelet or warfarin interruption.

Patients on anticoagulant or antiplatelet therapy are often required to discontinue these medications before and during surgical or invasive procedures. In some cases, the patient stops the treatment without medical supervision. These situations may increase stroke risk. To identify the ischemic stroke and transient ischemic attack (TIA) prevalence related to length of time of discontinuation of antiplatelet or vitamin K antagonist therapy, in a group of inpatients from a specialized neurological hospital in Brazil. Cross-sectional, retrospective and descriptive study of stroke inpatients for three years. Medical reports were reviewed to find study participants, stroke characteristics, risk factors, reasons and time of drug interruption. In three years, there were 360 stroke and TIA inpatients, of whom 27 (7.5%) had a history of antiplatelet or vitamin K antagonist interruption correlated with the time of the event (81% ischemic stroke, 19% TIA). The median time between antiplatelet interruption and an ischemic event was five days, and 62% of events occurred within seven days after drug suspension. For vitamin K antagonists, the average time to the ischemic event was 10.4 days (SD = 5.7), and in 67% of patients, the time between drug discontinuation and the event was 7-14 days. The most frequent reason for drug suspension was patient negligence (37%), followed by planned surgery or invasive examination (26%) and side effects, including hemorrhage (18.5%). Antiplatelet or vitamin K antagonist suspension has a temporal relationship with the occurrence of stroke and TIA. Since these events are preventable, it is crucial that healthcare professionals convince their patients that drug withdrawal can cause serious consequences.

Interruption of long-term warfarin is not necessary in patients undergoing total hip arthroplasty

IntroductionThe management of anticoagulation in patients undergoing arthroplasty remains a challenge. Guidelines for perioperative management of long-term warfarin recommend discontinuation of warfarin preoperatively in low risk patients. We hypothesised that patients who had their warfarin continued during the perioperative period would have shorter hospital stay and no significant increase risk of surgical complications compared to patients who had their warfarin interrupted. MethodsThis was a retrospective review of 20 consecutive patients receiving long-term warfarin who underwent total hip replacement without stopping warfarin. As a control group, we collected same data from 20 age and gender matched patients also on long term warfarin but their warfarin was stopped prior to surgery and restarted postoperatively. ResultsThere was no significant difference in age, BMI or comorbidities between the 2 groups. There was a statistically significant difference between the two groups in postoperative INR (P < 0.0001) levels. The mean drop in Hb postoperatively was 25.95 g/L in the warfarin group and 35.7 g/L in the control group, which was statistically significant (P = 0.0066). Hospital stay was statistically significant with shorted stay observed in the warfarin group (P = 0.0447). The odds ratio for developing a postoperative complication was 1.5882 which was not statistically significant (P = 0.6346). ConclusionOur results support the hypothesis that it is safe to continue warfarin in patients on long term anticoagulation undergoing total hip replacement. Continuation of warfarin was associated with significantly shorter hospital stay and less INR fluctuations. There was no significant increase in the risk of complications or blood transfusion.

Quality Assessment of Oral Anticoagulation by Time in Therapeutic Range in Patients with Venous Thromboembolism in Korea

Purpose To assess the efficacy and safety of oral anticoagulation with warfarin by time in therapeutic range in patients with venous thromboembolism (VTE) in South Korea. Methods This was a retrospective, single-center study to evaluate patients diagnosed with VTE and managed with adjusted dose of warfarin over two-thirds of follow-up period in Thrombosis Clinic between February 2009 and August 2010. Validated dosing algorithm was used to manage the international normalized ratio (INR). Time in therapeutic range was calculated by Rosendaal method. Results The period of predetermined warfarin interruption for peri-operative management (1 week preoperatively and 3 weeks post-operatively) was censored. It was not analyzed in 34 episodes. Out of 76 patients with VTE, 47 (23 men; mean age 64.9 years) were analyzed. Approximately two-thirds (31/47) of patients were warfarin-naïve. Total number of admissions was 84. Expected duration of anticoagulation was 6 months in 22 patients (47%), 12 months in 1 (2%), and indefinite in 24 (51%). There were various comorbidities, including active malignancy in 7 patients (15%), mycobacterium tuberculosis on rifampicin in 4 (8.5%), chronic kidney disease in 4 (8.5%), and hemorrhagic cerebral infarct in 1 (2%). Overall time in therapeutic range (TTR) was 52.4%. Most proportion of out-of-range was below the therapeutic range (29.5%). There was no thromboembolic complication, although two cases of major bleeding complications were observed. Conclusion The validated dosing algorithm is effective for managing INRs in patients with VTE in Korea. Keywords: Time in therapeutic range, Warfarin, International normalized ratio, Venous thromboembolism

THE IMPACT OF TEMPORARY INTERRUPTIONS OF WARFARIN ON DOWNSTREAM TIME IN THERAPEUTIC RANGE IN PATIENTS WITH ATRIAL FIBRILLATION: RESULTS FROM ORBIT AF

Temporary interruption (TI) of warfarin in atrial fibrillation (AF) may be associated with subsequent sub- or supra-therapeutic INR. Our objective was to study time in therapeutic range (TTR) before and after a TI. AF patients on warfarin who had a TI followed by resumption in the Outcomes Registry

Cost-Effectiveness of Bridging Anticoagulation Among Patients with Nonvalvular Atrial Fibrillation.

Bridging anticoagulation is commonly prescribed to patients with atrial fibrillation during initiation and interruption of warfarin. Guidelines recommend bridging patients at high risk of stroke, while a recent randomized trial demonstrated overall harm in a population at comparatively low risk of ischemic stroke. Theory suggests that patients at high risk of stroke and low risk of hemorrhage may benefit from bridging, but data informing patient selection are scant. To estimate the utility and cost-effectiveness of bridging anticoagulation among patients with nonvalvular atrial fibrillation, stratified by thromboembolic and hemorrhagic risk DESIGN: Cost-effectiveness analysis with lifelong time horizon, from the perspective of a third-party payer MAIN MEASURES: Quality-adjusted life years (QALYs) per bridged patient; US dollars per QALY gained KEY RESULTS: Unselected patients with nonvalvular atrial fibrillation may be harmed by bridging anticoagulation. Hospital admission for bridging is almost never cost-effective, and generally harmful. Among patients carefully selected by both thromboembolic and hemorrhagic risks, outpatient bridging can be beneficial and cost-effective. Results were sensitive to how effectively heparin products reduce stroke risk. Outpatient bridging anticoagulation can be beneficial and cost-effective for a subset of patients with nonvalvular atrial fibrillation during interruption or initiation of warfarin. Admission for bridging should be avoided.

Double Blind Randomized Control Trial of Postoperative Low Molecular Weight Heparin Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism (PERIOP 2)

▪BackgroundIt remains uncertain if patients with atrial fibrillation or mechanical heart valves requiring interruption of warfarin for procedures benefit from post-procedure anticoagulant bridging therapy.MethodsIn order to determine the efficacy and safety of postoperative LMWH bridging, we conducted a multicenter randomized double-blind controlled trial of patients with atrial fibrillation or a mechanical heart valve who require interruption of warfarin for a planned procedure. We excluded patients with active bleeding within 30 days, platelet count <100 x10⁹/L, spinal, cardiac or neurosurgery, life expectancy <3months, creatinine clearance <30ml/min, multiple mechanical valves or a Starr-Edwards valve, mechanical valve with history of stroke or TIA, or a history of heparin induced thrombocytopenia. The last dose of warfarin was given 6 days prior to the procedure. All patients received pre-procedure bridging therapy with dalteparin 200 IU per kilogram (max 18,000 IU) subcutaneously in the morning day-3 and day-2 then dalteparin 100 IU per kilogram (max 18,000 IU) subcutaneously 24 hours pre-procedure. Warfarin was resumed in the evening of the procedure at twice the usual dose for the first two days and then titrated according to INR. After the procedure (same day or next day), when hemostasis had been achieved, patients were randomized to receive dalteparin or placebo for at least 4 days and until the INR was greater than 1.9. Randomization was stratified by presence of a mechanical valve, by the post-procedure risk for major bleeding, and by centre. For patients at high risk for post-procedure major bleeding, dalteparin or placebo was administered at a fixed daily dose of 5000 IU. For patients at low risk for post-procedure major bleeding, dalteparin or placebo was administered at a daily dose of 200 IU per kilogram (max 18,000 IU). The primary analysis was a comparison of the proportion of patients who had major thromboembolism (stroke, proximal DVT, PE, MI, peripheral embolism) over 90 days by Chi-squared test according to the intention to treat principle. Secondary outcomes were major bleeding, all cause mortality and a composite outcome of major thromboembolism and major bleeding.ResultsStarting in October 2006 we randomized a total of 1471 patients of whom 1167 had atrial fibrillation (without mechanical heart valves) and 304 had mechanical valves (99 also had atrial fibrillation). Last follow up was completed in May 2016. Baseline characteristics were similar between the LMWH and the placebo groups (see Table 1). Due to a randomization program system error at two centres more atrial fibrillation patients were randomized to dalteparin rather than to placebo. Major thromboembolism occurred in 6/820 (0.71%) dalteparin patients and 7/650 (1.11%) placebo patients. Major post-procedure bleeding occurred in 12 (1.46%) dalteparin patients and 16 (2.46%) placebo patients. Findings were similar in patients with atrial fibrillation alone and in patients with mechanical heart valves (with or without atrial fibrillation) (Table 2).ConclusionsIn patients with atrial fibrillation and/or mechanical heart valves who had warfarin interrupted for a procedure there was no benefit from post-procedure LMWH bridging. [Display omitted] DisclosuresKovacs:Bayer: Research Funding; Daiichi Sankyo Pharma Development: Research Funding. Wells:Janssen: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Bayer: Honoraria. Schulman:Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.

Thrombotic and Bleeding Outcomes Following Perioperative Interruption of Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Non-Valvular Atrial Fibrillation - a Comparative Analysis

Background: Atrial fibrillation (AF) is a common disorder that will affect up to 5.6 million patients in the U.S. by 2050. Both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), typically warfarin, are used for stroke prevention in AF and such patients frequently undergo invasive procedures requiring anticoagulant interruption. Temporary interruption of anticoagulants can be associated with significant morbidity and mortality in the form of thromboembolic and bleeding complications. DOACs have a short half-life and fast onset of action, thereby facilitating their perioperative management as compared to VKAs. Despite important differences in perioperative management and pharmacokinetics between DOACs and VKAs, there is a paucity of data comparing perioperative outcomes in DOAC and VKA-treated patients.Methods: We undertook a single-center, retrospective chart review that compared consecutive DOAC- or warfarin-treated patients with AF who underwent perioperative anticoagulant interruption for invasive procedures between January 2017 and March 2018. Perioperative warfarin interruption was done as per CHEST guidelines (Douketis et al. Chest 141,2 Suppl). Perioperative bridging with low-molecular-weight heparin was only used for patients with CHADS2 scores of 5-6 or in patients with stroke within the past 6 months. Perioperative interruption of DOACs was done as per Thrombosis Canada guidelines, with anticoagulation held for 3 half-lives prior to low bleeding risk procedures and 5 half-lives for high bleeding risk procedures. Primary outcomes included the 30-day post-operative thromboembolic and major bleeding rates. Secondary outcomes included the 30-day clinically relevant non-major bleeding (CRNMB) andl mortality rates. Major bleeding and CRNMB were defined according to ISTH definitions. Procedural bleeding risk was defined as per Schulman et al (Circulation 2015; 132(3)). Outcome events were independently adjudicated by two investigators. Outcomes from patients on DOACs and VKAs were compared. Demographic data was analyzed on a per-patient basis, p-values were calculated using independent T-Test, Chi-Square/Fisher's Exact Test where appropriate. Outcome data was analyzed on a per-interruption basis. P-values for unadjusted and adjusted comparisons were calculated using generalized estimating equations (GEE) to account for correlation between multiple procedures on the same patients.Results: 325 DOAC patients and 199 warfarin patients underwent 351 and 221 periprocedural interruptions, respectively. Warfarin patients had a significantly higher mean age, CHADS2 score, and proportion with renal dysfunction (Table 1). There was no statistically significant difference in 30-day post-operative rates of thromboembolism, CRNMB, and overall mortality, but warfarin patients had a significantly higher rate of major bleeding (Table 2). This latter result remained statistically significant following multivariate logistic regression correction for age, CHADS2 score and level of renal dysfunction. All bleeding events occurred post-procedure, with major bleeding events occurring from post-operative day 1 to post-operative day 25. None of the warfarin patients with major bleeding received perioperative bridging; the mean international normalized ratio (INR) at the time of major bleeding was 3.3. Most major bleeding events (7/8) in the VKA arm were surgical, with a single non-surgical major-bleed (spontaneous ICH on post-operative day 15 following urological surgery).Conclusions: The perioperative interruption of warfarin was associated with a higher 30-day rate of major bleeding as compared with DOAC interruption. Re-initiation of warfarin should be done judiciously following high bleeding risk procedures, and close INR monitoring may be warranted. [Display omitted] DisclosuresShaw:Portola Pharmaceuticals: Research Funding. Douketis:Janssen: Consultancy; Pfizer: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; Portola: Other: Advisory Board; The Medicines Company: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Biotie: Other: Advisory Board; Bayer: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; BMS: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board. Carrier:Bayer: Honoraria; Pfizer: Honoraria; BMS: Honoraria, Research Funding; Leo Pharma: Research Funding.

Clinical events after interruption of anticoagulation in patients with atrial fibrillation: An analysis from the ENGAGE AF-TIMI 48 trial

BackgroundPatients with atrial fibrillation (AF) who interrupt anticoagulation are at high risk of thromboembolism and death. Methods and resultsPatients enrolled in the ENGAGE AF-TIMI 48 trial (randomized comparison of edoxaban vs. warfarin) who interrupted study anticoagulant for >3 days were identified. Clinical events (ischemic stroke/systemic embolism, major cardiac and cerebrovascular events [MACCE]) were analyzed from day 4 after interruption until day 34 or study drug resumption. During 2.8 years median follow-up, 13,311 (63%) patients interrupted study drug for >3 days. After excluding those who received open-label anticoagulation during the at-risk window, the population for analysis included 9148 patients. The rates of ischemic stroke/systemic embolism and MACCE post interruption were substantially greater than in patients who never interrupted (15.42 vs. 0.26 and 60.82 vs. 0.36 per 100 patient-years, respectively, padj < .001). Patients who interrupted study drug for an adverse event (44.1% of the cohort), compared to those who interrupted for other reasons, had an increased risk of MACCE (HRadj 2.75; 95% CI 2.02–3.74, p < .0001), but similar rates of ischemic stroke/systemic embolism. Rates of clinical events after interruption of warfarin and edoxaban were similar. ConclusionInterruption of study drug was frequent in patients with AF and was associated with a substantial risk of major cardiac and cerebrovascular events over the ensuing 30 days. This risk was particularly high in patients who interrupted as a result of an adverse event; these patients deserve close monitoring and resumption of anticoagulation as soon as it is safe to do so.

Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: Analysis of the BRIDGE trial

The use of low-molecular weight heparin bridge therapy during warfarin interruption for elective surgery/procedures increases bleeding. Other predictors of bleeding in this setting are not well described. BRIDGE was a randomized, double-blind, placebo-controlled trial of bridge therapy with dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring warfarin interruption. Bleeding outcomes were documented from the time of warfarin interruption until up to 37 days postprocedure. Multiple logistic regression and time-dependent hazard models were used to identify major bleeding predictors. We analyzed 1,813 patients of whom 895 received bridging and 918 received placebo. Median patient age was 72.6 years, and 73.3% were male. Forty-one major bleeding events occurred at a median time of 7.0 days (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9). Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent predictors of major bleeding. Major bleeding was most common in the first 10 days compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). In addition to bridge therapy, perioperative aspirin use, postprocedure international normalized ratio >3.0, a history of renal failure, and having a high-bleeding risk procedure increase the risk of major bleeding around the time of an elective surgery/procedure requiring warfarin interruption.

A randomized trial of restarting warfarin at maintenance versus loading doses following an elective procedure.

Guidelines suggest restarting warfarin at known maintenance doses, although this may result in a delay to achieving therapeutic anticoagulation. As such, we compared the time to achieve an INR ≥ 2.0 between those restarting warfarin maintenance vs loading doses after transient interruption, and the impact on protein C, S and factor II levels. Patients requiring interruption of warfarin for elective procedures without hospitalization were randomized 1:1 to receive warfarin maintenance or loading doses (1.5 times the maintenance dose for 3 days followed by pre-procedural warfarin maintenance dosing). Protein C, S and Factor II were drawn at baseline (prior to warfarin interruption), 7 and 14 days after restarting warfarin. Among 19 patients randomized to maintenance and 20 to loading doses, nearly half in each group had mechanical heart valves with gastrointestinal endoscopic procedures most commonly performed (41%). The median number of days to reach an INR ≥ 2.0 was 7.8 days in the loading and 9.0 in the maintenance group (difference between medians 1.2 days, 95% CI -3.1 to 4.9; P = 0.19). Although levels of protein C, S and factor II were lower in the loading vs maintenance dose group, all remained above that of baseline. Warfarin resumption with loading doses shortened the time to achieve a therapeutic INR by a median of 1.2 days. Prompt warfarin dose escalation should be done in response to the INR. Protein C and S remained above pre-warfarin interruption levels, implying a lack of depletion with restarting warfarin.

Perioperative Heparin Bridging in Atrial Fibrillation Patients Requiring Temporary Interruption of Anticoagulation: Evidence from Meta-analysis

Patients with atrial fibrillation (AF) often require temporary interruption of warfarin for an elective operation or invasive procedure. However, the safety and efficacy of periprocedural bridging anticoagulation with unfractionated heparin (UH) or low-molecular-weight heparin (LMWH) are still unclear. We evaluated the safety of periprocedural heparin bridging in AF patients requiring temporary interruption of oral anticoagulation. We searched the literature for trials that compared heparin bridging with no bridging in AF patients for whom warfarin was temporarily interrupted. The incidence of all-cause mortality, thromboembolism, and major and all bleeding was included, and meta-analysis was performed. A total of 13,808 patients with AF were included in 4 observational studies, 1 randomized trial, and 1 subgroup analysis of a randomized trial. The mean CHADS2 score for the no heparin bridging group was 2.49 and that for the heparin bridging group was 2.34. At 30 days and up to 3 months, when compared to the heparin bridging group, the no bridging group did not have any significant difference in mortality (odds ratio [OR], 1.29; 95% confidence interval [CI], .15-11.52; P = .82) or cerebrovascular accidents (OR, .93; 95% CI, .34-2.51; P = .88), but the no bridging group had significantly less major bleeding (OR, .41; 95% CI, .24-.68; P = .0006). Among AF patients with intermediate CHADS2 scores who are anticoagulated with warfarin and who required temporary interruption of warfarin for an elective surgery or procedure, periprocedural bridging with UH or LMWH was associated with a higher rate of major bleeding with no significant difference in mortality or CVA.

The BRIDGE trial: What the hospitalist should know.

Atrial fibrillation patients often require warfarin interruption for an invasive procedure or surgery. Heparin bridging therapy has been frequently used during warfarin interruption under the premise of providing a theoretical mitigation against thromboembolism that overweighs expected higher rates of bleeding. Up until recently, little definite clinical evidence was available to guide the hospitalist on optimal perioperative anticoagulant management. The landmark BRIDGE (Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation) trial provided high-quality evidence that a simple interruption of warfarin in the average atrial fibrillation patient undergoing an elective procedure or surgery is noninferior to bridging therapy for efficacy and superior to bridging therapy in preventing major bleeding. To guide the hospitalist, we propose a treatment algorithm based on these recent data. We review the literature that led to the trial and highlight its practice-changing implications as a proof of concept that calls to question the premise of heparin bridging therapy beyond the atrial fibrillation population. Journal of Hospital Medicine 2016;11:652-657. © 2016 Society of Hospital Medicine.

Prothrombin Complex Concentrate for Non-Bleeding Urgent Warfarin Reversal in Ventricular Assist Device Patients Undergoing Heart Transplantation

Due to unpredictable donor heart availability, bridge-to-transplant ventricular assist device (BTTVAD) patients are likely therapeutically anticoagulated on warfarin and require non-bleeding urgent anticoagulation reversal before heart transplantation. We describe 4-factor prothrombin complex concentrate (4F-PCC) use for this indication. This single center, retrospective chart review included BTTVAD patients who received a heart transplant at Brigham and Women’s Hospital (BWH) from December 2013 to November 2014. Patients who did not receive 4F-PCC were excluded. Twelve BTTVAD patients (mean age 54 years, 58 % male, INR of 2.7 ± 0.8) were admitted for urgent heart transplantation. To reverse the INR prior to surgery, patients received a combination of interruption of warfarin and administration of vitamin K, 4F-PCC, and fresh frozen plasma (FFP). All patients received vitamin K at varied routes and doses along with 3 ± 2 units of FFP. Patients received 4F-PCC 25–50 units/kg IV before surgery, and most INR values were less than 2.0 within 1 h of surgical incision. Anticoagulation was effectively reversed with an INR of 1.4 ± 0.1 at completion of surgery. Zero patients required reoperation for bleeding, and there was one death within 30 days. Our results suggest that 4F-PCC 25–50 units/kg IV with vitamin K will achieve rapid, complete, and sustained anticoagulation reversal for BTTVAD patients requiring non-bleeding urgent warfarin reversal for heart transplant.

Prosthetic graft interposition of the brachiocephalic veins or superior vena cava combined with resection of malignant tumours: graft patency and risk factors for graft occlusion.

We aimed to assess graft patency in patients undergoing prosthetic graft interposition of the brachiocephalic veins (BCVs) or the superior vena cava (SVC) combined with resection of malignant tumours. A retrospective analysis was conducted on 16 patients who underwent prosthetic graft interposition of the BCVs or the SVC between 1998 and 2012. Among a total of 20 grafts in 16 patients (unilateral graft interposition in 12, bilateral graft interposition in 4), 8 grafts were occluded in 8 patients. Overall graft patency rate was 64.6%, 42.4% at the 2- and 5-year follow-up. Graft patency rate of the left BCV was significantly lower than that of the right BCV or the SVC (2-year patency, 38.1% vs. 81.8%, P=0.024). In univariate analysis, the superior anastomosis site [left BCV vs. right BCV; hazard ratio (HR) =2.312; 95% confidence interval (CI), 1.015-5.265; P=0.046], the inferior anastomosis site (right atrial appendage vs. SVC; HR =2.409; 95% CI, 1.124-5.161; P=0.024), and interruption of warfarin (HR =5.015; 95% CI, 1.106-22.734; P=0.037) were significant risk factors for graft occlusion. Graft occlusive symptoms were identified in 4 patients who underwent unilateral graft interposition. Prosthetic graft interposition between the left BCV and the right atrial appendage resulted in a significant rate of graft occlusion. Prosthetic graft interposition of the bilateral BCVs and long-term warfarin therapy may be necessary to prevent graft occlusive symptoms.

Bridging anticoagulation for interruption of warfarin in a patient with atrial fibrillation

A 78-year-old man with chronic nonvalvular atrial fibrillation presents to his family physician three weeks before a transurethral resection of the prostate for benign prostatic hypertrophy. His history includes hypertension and type 2 diabetes. He has no history of congestive heart failure, stroke

Abstract 16339: Heparin Bridging in Atrial Fibrillation Patients After Temporary Interruption of Warfarin: Evidence From Meta-analysis

Background: Patients with atrial fibrillation often require temporary interruption of warfarin for procedures. However, the efficacy of periprocedural heparin bridging in clinical practice is still unclear. Methods: We searched the literature for trials that compared heparin bridging to no bridging in atrial fibrillation patients for whom warfarin was temporarily interrupted. The incidence of all-cause mortality, thromboembolism, and major and all bleeding was included, and meta-analysis was performed. Results: A total of 11,924 patients with atrial fibrillation were included in 4 observational studies and 1 randomized trial. Mean CHADS2 score for the no heparin bridging group is 2.26 vs heparin bridging 2.26. At 30 days and up to 3 months, no bridging group in comparison to bridging group did not show any significant difference in mortality (odds ratio (OR), 1.22; 95% confidence interval (CI), 0.04-37.43; P = 0.91) or thromboembolism (OR, 0.69; 95% CI, 0.12-4.05; P = 0.68), but no bridging group showed significantly less major bleeding (OR, 0.43; 95% CI, 0.21-0.86; P = 0.02) and less all bleeding (OR, 0.43; 95% CI, 0.24-0.79; P = 0.007). Conclusion: Among atrial fibrillation patients anticoagulated with warfarin with an intermediate CHADS2 score requiring temporary interruption of warfarin for a procedure, periprocedural bridging with heparin was associated more with major and all bleeding when compared to no bridging, with no significant difference in mortality and thromboembolism.

ACP Journal Club: in AF requiring warfarin interruption, no bridging was noninferior to anticoagulation bridging for thromboembolism.

Source Citation Douketis JD, Spyropoulos AC, Kaatz S, et al; BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373:823-33. 26095867

Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures

CONCLUSIONS AND RELEVANCE Bridge therapy was associated with an increased risk of bleeding during warfarin therapy interruption for invasive procedures in patients receiving treatment for a history of VTE and is likely unnecessary for most of these patients. Further research is needed to identify patient- and procedure-related characteristics associated with a high risk of perioperative VTE recurrence during warfarin therapy interruption.

Safety of Uninterrupted Warfarin Therapy in Patients Undergoing Cardiovascular Endovascular Procedures: A Systematic Review and Meta-Analysis.

To conduct a systematic review and meta-analysis of complication rates and outcomes in patients undergoing endovascular procedures who receive uninterrupted versus interrupted warfarin therapy. Literature published between 1990 and 2014 was searched for reports of comparative studies of vascular procedures. Information on periprocedural complications and patient deaths less than 30 days after the procedure was extracted. A random effects model was used and odds ratios (ORs) were reported. An OR of less than 1 was considered to indicate lower risk of the outcome with uninterrupted warfarin therapy. Meta-analysis was conducted by using meta-analysis software. A total of 27 studies of 20,376 patients were included. For arterial procedures, there were no significant differences between the uninterrupted and interrupted warfarin therapy groups in access site hematoma (OR, 0.59; 95% confidence interval [CI]: 0.33, 1.03; P = .06), any bleeding complications (OR, 0.56; 95% CI: 0.30, 1.06; P = .07), mortality (OR, 1.40; 95% CI: 0.37, 5.25; P = .62), intracranial hemorrhage (OR, 0.55; 95% CI: 0.03, 8.91; P = .68), ischemic stroke (OR, 0.85; 95% CI: 0.12, 5.84; P = .87), and major bleeding (OR, 0.56; 95% CI: 0.21, 1.51; P = .25). For venous procedures, uninterrupted warfarin was associated with lower odds of access site hematoma (OR, 0.70; 95% CI: 0.50, 0.99; P = .04), any bleeding complications (OR, 0.61; 95% CI: 0.48, 0.77; P < .01), ischemic stroke (OR, 0.21; 95% CI: 0.10, 0.45; P < .01), and major bleeding (OR, 0.64; 95% CI: 0.51, 0.80; P < .01). For arterial and venous procedures combined, uninterrupted warfarin was associated with lower odds of access site hematoma (OR, 0.68; 95% CI: 0.51, 0.91; P = .01), bleeding complications (OR, 0.59; 95% CI: 0.48, 0.74; P < .01), ischemic stroke (OR, 0.25; 95% CI: 0.12, 0.50; P < .01), and major bleeding (OR, 0.61; 95% CI: 0.49, 0.77; P < .01). Heterogeneity in most analyses was low, and confidence in the estimates was moderate. Uninterrupted perioperative warfarin therapy is safe for patients undergoing arterial procedures, but interrupted warfarin may be preferred for those undergoing venous procedures; no differences in outcome rates were found in the randomized controlled trials. Future studies should be performed to validate these results.