alvin goo- perioperative bridge · 11/3/2015 6 recommendations for major surgery • discontinue...

11/3/2015

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Peri‐Operative Bridging WSPA Annual MeetingNovember 21 th 2015

Alvin Goo, Pharm.D. Clinical Associate Professor

University of Washington School of Family Medicine and Pharmacy

Speaker Declaration

• Dr. Goo declares that neither he, nor any member of his family, has had a financial interest, arrangement or affiliation with an organization providing support for this continuing medical education activity.

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Objectives

• Analyze the evidence regarding perioperative bridging with low molecular weight heparin and newer oral anticoagulants

• Discuss the limitations of the evidence regarding perioperative bridging

• Assess the hemorrhagic and thrombotic risk of perioperative bridging

• Apply your knowledge of perioperative bridging when providing your recommendations

Discussion• Options for perioperative anticoagulation?

o Continue therapeutic Vitamin K Antagonist (VKA)

o Hold VKA with Low Molecular Weight Heparin (LMWH therapeutic dosing) bridging before and after

o Hold VKA with LMWH bridging (therapeutic or low dose) after procedure

o Hold VKA with LMWH bridging (therapeutic or low dose) prior to procedure

o Hold VKA without bridging

• Should we bridge with LMWH?

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CHEST Guidelines

• Lack of randomized trials to guide practice

Douketis JD et al. CHEST 2012;141(2):e326S‐e350S

TE Risk Management recommendations during interruption of VKA

Grade of Evidence

High Bridge 2C

Moderate Bridge or No‐bridge approach based on assessment of individual patient and surgery‐related risk factors

N/A

Low No Bridge 2C

TE = Thromboembolism

CHEST GuidelinesLevel of Risk

AnnualTE Rate

Mechanical heart valve AFib Venousthromboembolsim(VTE)

High >10% MVRCaged‐ball or tilting disk AVRRecent (w/in 6 mo) Stroke/TIA

CHADS2 = 5 or 6Recent (w/in 3 mo) stroke/TIARheumatic valvularheart disease

Recent (w/in 3 mo) VTESevere thrombophilia (deficient protein C or S, antiphospholipid)

Mod 5‐10% Bileaflet AVR and 1+ of the following: AF, stroke/TIA, HTN, DM, CHF, age > 75

CHADS2 = 3 or 4 VTE in past 3‐12 moNon‐severe thrombophilia (Factor V Leiden)Recurrent VTEActive cancer

Low <5% Bileaflet AVR w/o AF or other risk factors for stroke

CHADS2= 0‐2, with no prior stroke/TIA

VTE > 12 months ago, no other risk factors


Hemorrhagic Risk

High Risk Moderate Risk Low Risk

AA repairUrologic surgery/proceduresNephrectomy or kidney biopsyProstate surgeryPolypectomy, especially >1‐2cmOrgan surgeryBowel resectionCardiac surgery, CABGMajor orthopedic surgeryInter cranial or Spinal surgery/ Epidural procedure

Renal biopsyColon polyp resectionPacemaker / DefibplacementInvasive dental or Ophthalmic procedure

Cataract surgeryDental procedureCutaneous surgery


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Hemorrhagic Risk Factors

• Bridging with heparin

• Re initiation of heparin within 24 hours

• Mitral valve replacement

• Active cancer

• History of prior bleeding

Tafur AJ et al. J Thromb Haemost 2012;10(2):261‐267

HAS‐Bled

• Hypertension SBP > 160 1• Abnl renal or liver function

o Chronic dialysis, renal transplant, Sc ≥ 2.3 1o Cirrhosis, Bili > 2x ULN w/ LFT > 3x ULN 1

• Stroke 1• Bleeding hx or anemia 1• Labile INR 1• Elderly > 65yrs old 1• Drugs

o Antiplatelet agent or NSAIDs 1o ETOH >8 drinks/week 1

Dental Case

• 64 yr old female anticoagulated with warfarin for a‐fib and scheduled for dental extractions and dental bridge.

• No history of previous stroke or TIA

1. Discontinue warfarin 5 days prior to procedure and bridge with Enoxaparin 1mg/kg Q12

2. Continue warfarin, use prohemostatic mouthwash

3. Continue warfarin

4. Stop warfarin 2 days before procedure and resume after the procedure

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Recommendation

• Minor dental surgery: o Continue warfarin with co administration of prohemostaticagent

Or

o Discontinuation of warfarin 2‐3 days before the procedure and resume after the procedure

Grade 2C

University of Washington Anticoagulation Clinic

http://depts.washington.edu/anticoag/home/node/3


Dental Procedure

Low bleeding risk Moderate bleeding risk High bleeding risk

Supraginival scalingSimple restorationsLocal anesthetic injections

Subgingival scalingRestorations (subgingival)Root canalExtractionsRegional anesthetic injections

Root removal(apicoectomy) Bone removalMultiple extractions

Manage dental bleeding

Compression (gauze, tea bag) Gelatin sponge Gelfoam, Surgicel, Avitene

SuturingElectrocauteryThrombin powderTranexamic acid rinse 5%Aminocaproic acid rinse5%

http://depts.washington.edu/anticoag/home/content/local‐methods‐prevent‐or‐control‐bleeding

Mitral Valve Case

• 56 yo female is schedule for Colonoscopy due to hematochezia.

• Hx: A‐fib, Rheumatic heart disease, MVR

1. Discontinue warfarin 5 days prior to procedure and bridge with Enoxaparin 1mg/kg Q12 pre and post

2. Discontinue warfarin 5 days prior and bridge with low dose LMWH pre and post

3. Discontinue warfarin 5 days pre op and resume after procedure

4. Continue 50% of warfarin starting 5 days preop

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Recommendations for Major Surgery

• Discontinue warfarin 5 days prior to surgery (Grade 1C)

• Resume warfarin 12‐24 hrs after surgery (evening of or next morning) (Grade 2C)

• Patients with mechanical heart valve, afib or VTE at high risk for thromboembolism: suggest Bridging (Grade 2C)


Last dose

No for Major Surgery

3

Resume LMWH 24hrs after procedure

Start LMWH

ResumeWarf evening After surg

Resume LMWH 24hrs after Procedure High risk bleeding

Major Surgery Case

• 64 yo female is scheduled for bariatric surgery (BMI 60)

• Hx Afib currently anticoagulated with warfarin

o Type 2 Diabetes managed by diet (Ha1c 6.5%, Macro 950)

o Hypertension

o Sleep apnea

o Hypothyroidism

o Dyspepsia

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Options

• Discontinue warfarin 5 days preop, provide LMWH bridging (therapeutic) pre and post op

• Discontinue warfarin 5 days preop, administer low dose LMWH pre and post op

• Continue warfarin but reduce by 50% starting 5 days preop

• Stop warfarin 5 days preop and resume after procedure and consider LMWH post op if immobile

StudiesCohort Study Type Patients Procedure(s)

Wysokinski et al. 2008

Pro 345 patients with AFCHADS2 = 1.9‐2.2History of stroke = 24‐43%History of CAD = 28‐47%

Various (21% orthopedic, 20% GI, 18% urologic, 14% cardiovascular, etc.)

Garcia et al. 2008 (ACTION)

Pro 1024 patients53% AF (83% CHADS2=0‐2, 14% CHADS2=3, 3% CHADS2>4)15% VTE13% MHV (40% MVR)9% history of stroke7% considered “high risk for TE”

1293 minor outpatient surgeries (colonoscopy, dental, ophthalmologic)

Ahmed et al. 2010

Ret 459 patientsAF 70‐90% (CHADS2=2.5‐2.6)MHV 1‐19%VTE 5‐10%

Pacemaker or ICD implant

Wysokinski WE et al. Mayo Clin Proc 2008;83(6):639‐645Garcia DA et al. Arch Intern Med 2008; 168(1):63‐69

Ahmed I et al. Heart Rhythm 2010;7(6):745‐749

StudiesCohort Study Bridging Strategy Outcomes (no bridge v bridge)

Wysokinski et al. 2008

Patient TE Risk:Low = hold VKA w/o bridgeHigh = hold VKA + bridgeProcedure Bleed Risk:High = interrupt VKALow = continue VKA

90‐day symptomatic TE:1.8% v 1.5%90‐day major bleed:2.3% v 3.0%90‐day minor bleed:1.1% v 4.6%

Garcia et al. 2008 (ACTION)

92% held w/o bridge, 8% bridged (near‐exclusively LMWH)AF: 3% bridgedVTE: 10% bridgedMHV: 29% bridged

30‐day TE: 0.6% v 0%30‐day major bleed:0.2% v 3.7%30‐day “significant” bleed:0.6% v 9.3%

Ahmed et al. 2010

Compared 3 strategies:Continue warfarinHold warfarin + bridgeHold warfarin w/o bridge

Hematoma: 0.5% v 5.7% v 1.8%TIA: 0% v 0.8% v 3.5%Hospital LOS (d): 1.2 v 2.3 v 1.2

Wysokinski WE et al. Mayo Clin Proc 2008;83(6):639‐645Garcia DA et al. Arch Intern Med 2008; 168(1):63‐69

Ahmed I et al. Heart Rhythm 2010;7(6):745‐749

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Endoscopic Bridging Considerations

Diagnostic / Screening Moderate –High thrombotic risk

Low thrombotic risk

Low biopsy riskDiagnosticRemoval of polyps <1cmpolyps (< 3)

Continue warfarin Consider holding warfarinand proceed when INR< 1.5

Large polyp removal(>1 cm)

Hold warfarin and periprocedural bridge anticoagulation

Consider holding warfarinand proceed when INR< 1.5

SphicterotomyEsophageal dilationFine needle aspiration

Hold warfarin and periprocedural bridge anticoagulation

Consider holding warfarinand proceed when INR< 1.5

Endoscopy Case• 66yo male Hx of A‐fib, HTN. No hx of stroke or TIA, DM, vascular disease, or CHF. Scheduled for a repeat colonoscopy and possible polypectomy (previous colonoscopy 2 polyps resected)

1. Discontinue warfarin 5 days prior to procedure and bridge with Enoxaparin 1mg/kg Q12 pre and post

2. Discontinue warfarin 5 days prior and bridge with low dose LMWH pre and post

3. Discontinue warfarin 5 days pre op and resume after procedure

4. Continue warfarin at therapeutic dose

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Endoscopy Case

• Bleeding risk of procedure:

o High if polypectomy > 1cm

• Thrombotic risk:

o Afib, HTN

o CHADS2 = 1

• Options

o Bridge

o Hold warfarin (4‐5 days)

o Continue therapeutic warfarin

Endoscopic Biopsy

• Consecutive pts currently receiving antithromboticswere evaluated

• GI endoscopy indication: cancer screening, examination of bleeding or anemia

• 1034 pt underwent EGD while taking antithrombotics

• ASA 44.8%

• Warfarin 34.7%

• Thienopyridine 16.1%

• Dabigatran 4.8%

Fujita M, et al. Dig endoscopy 2015;27(1):25

Results

• 359 pts taking warfarin

• Endoscopic biopsy were carried out on 206 ptsreceiving warfarin

• Mean INR 1.77± 0.67 (range 0.98‐5.98)

• Hemostatic procedures after biopsy was required:

3/206 pts receiving warfarin 1.5%

34/3465 control pts 0.98%

p=0.51

Fujita M, et al. Dig endoscopy 2015;27(1):25

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Pacemaker Case• 65 yr African American with uncontrolled A‐fib, HTN, type 2 diabetes, stroke 4 years ago. Afib remains uncontrolled and pt is symptomatic. Failed to respond to cardioversion (electrical and pharmacotherapy) is scheduled for pace maker placement.

Pacemaker Implantation

• 65 yo male with Afib is scheduled for pacemaker implant.

• Hx HTN, Afib, new onset DM, previous stroke

• No Hx of CHF

• Options: o Continue warfarin during procedure

o Discontinue warfarin and bridge with LMWH pre and post procedure

o Discontinue warfarin and bridge with LMWH post procedure

o Reduce warfarin by 50% prior to procedure

BRUISE Control 2013

• Randomized, non‐blinded trial

• 681 patients with TE risk 5% or more undergoing pacemaker or ICD placement

o 88% AF (mean CHADS2= 3.4)

o 30% MHV (50% MVR, 50% bileaflet AVR)

o 5% VTE

• Continue warfarin vs. therapeutic‐dose bridging

Birnie DH et al. N Engl J Med 2013;368(22):2084‐2093

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BRUISE Control Results

• Terminated early (pre‐specified)

• TE : 1 stroke + 1 TIA in warfarin group, 1 MI in bridging group

Outcome Continuewarfarin n=338

Bridge N=343

P‐value

Pocket hematoma

3.5% 16% <0.001

Any TE 0.6% 0.3% NS

Prolonged hospitalization

1.2% 4.7% 0.006

Mortality 1.2% 0% 0.12 (NS)

Birnie DH et al. N Engl J Med 2013;368(22):2084‐2093

COMPARE Radiofrequency Ablation

• 1584 pts undergoing radiofrequency catheter ablation were randomized to: holding VKA with LMWH bridging and IV heparin, or continuation of VKA

• All pts receive IV heparin bolus prior to the trans septal puncture

• CHADS2 > 1

• INR 2‐3 3‐4 weeks prior to ablation

Di Biase L, et al. Circulation 2014;129:2638

COMPARE Results

Endpoint Bridge Warfarin maintained

p

N=790 N=794

Stroke or TIA 4.9% 0.25% <0.001

Stroke 3.7% 0.25% <0.001

TIA 1.3% 0 <0.001

Major bleeding

0.76% 0.38% 0.31

Minor bleeding

22% 4.1% <0.001

Di Biase L, et al. Circulation 2014;129:2638

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COMPARE

Bridge vs Uninterrupted Warfarin AFCA Registry

• Prospective registry that followed Pts with Afibundergoing Coronary Stenting

Uninterrupted AC n=290 Bridge n=161 P

Major CV events 11 (3.8%) 10 (6.2%) 0.25

Death 6 (2.1%) 4 (2.5%) 0.73

Stent thrombosis 6 (2.1%) 2 (1.2%) 0.72

All Bleeding 35 (12.1%) 30 (18.6%) 0.07

Major bleeding 4 (1.4%) 4 (2.5%) 0.25

Access site bleeding 16 (5.5%) 18 (11.2%) 0.03

Lahtela H, et al. Circ J 2012;76:1363

ORBIT‐AF Registry

• Outcomes Registry for Better Informed Treatment of A‐Fib

• No interruption n=5172

• No Bridge 1608

• Bridge 592

• Mean CHADS2 2.4

• Mean CHA2DS2‐VASc 4

Steinberg BA, et al. Circ 2015;3:131(5):488

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Unadjusted Outcomes

0

1

2

3

4

5

6

Total events Bleeding Thrombotic

Overall

No Bridge

Bridging


30 Day Postop Events

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

MI Embolism Major Bleed CVD hosp Bleed hosp

Overall

No Bridging

Bridging


Total Knee Arthroplasty

• Case control study in patients undergoing Total knee arthroplasty

• 61 warfarin and 61 control patients undergoing TKA

• INR 2‐2.2 on the day of surgery

• Indication for warfarin 54.1% a‐fib

• No difference in total transfusions rates

• No difference in total complications rates

Phillips A, et al. J Orthoped Surg and Research 2015;10:16

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BRIDGE Study

• Randomized patients with a‐fib undergoing an elective invasive procedure to Holding warfarin or Bridging

• Mean CHADs2 2.3

• Warfarin was held 5 days prior to procedure

• Warfarin restarted 1.5 days after procedure

Douketis J, et al. NEJM 2015;373:823

BRIDGE Study Results

Warfarin Held(918)

Bridge with LMWH(895)

Thromboembolism 4 (0.4%) 3 (0.3%) 0.01*

Stroke 2 (0.2%) 3 (0.3%)

Major Bleeding 12 (1.3%) 29 (3.2%) 0.005

Minor Bleeding 110 (12%) 187 (20.9%) 0.001

* Noninferiority

• Did not describe types of invasive procedures• Did not include continue warfarin arm

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Perioperative Bridging Options• High Risk Bleeding

o Interruption of warfarin is recommended

• Low Risk Bleedingo Continue warfarin anticoagulation

• High Risk for Thrombosiso Recommend Peri and post operative bridging

• Moderate Risk for Thrombosiso Further studies are needed to clarify the approacho Bridging with LMWH is associated with greater risk of bleedingo Discuss risk of thrombosis vs risk of hemorrhage o Consider holding warfarin (< 7 days total) or continue with warfarin during

procedure

• Low Risk for Thrombosiso Recommend avoiding bridging

• Minimize subtherapeutic days (< 5)

Bridging Regimens

• Therapeutic dose LMWH

o Enoxaparin 1mg/kg Q12 hr

• Intermediate dose

o Enoxaparin 40mg Q12h

• Low dose (prophylactic) LMWH

o Enoxaparin 40mg daily

Peri operative management of Newer Oral Anticoagulants

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RE‐LY Perioperative Bridging Outcomes Warfarin Dabigatran

Bridged (391) Not Bridged (1033)

Bridged (418)

Not Bridged (2291)

Any MajorBleeding

26 (6.6%) 16 (1.5%) 27 (6.5%) 42 (1.8%)

Life threatening Bleed

7 (1.8%) 5 (0.5%) 10 (2.4%) 12 (0.5%)

Fatal Bleed 0 2 (0.2%) 0 1 (0.0)

Stroke 2 (0.5%) 2 (0.2%) 2 (0.5%) 4 (0.2%)

PulmonaryEmbolism

2 (0.5%) 0 0 2 (0.1%)

Any thrombotic event

7 (1.8%) 3 (0.3%) 5 (1.2%) 13 (0.6%)

Douketis JD etal. Thromb Haemost 2014:113(3)

Dabigatran vs Warfarin Ablation AnticoagulationMeta Analysis

• 9 cohort studies, 1 case study

• Uninterrupted warfarin

• Dabigatran held 12‐24hrs prior to procedure

Shurrab M, et al. Canadian J Card 2013;29(10):1203

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Prospective Dresden NOAC Surgical or interventional procedures• Minimal:

o Superficial skin / oral mucosal surgeries, skin biopsieso Wound revisionso Non‐extraction dental procedures

• Minor relevant bleeding risko Transluminal cardiac, arterial and venous interventionso Pace maker related surgeryo Pleura and ascites punctureo Cataract surgeryo Arthroscopy, endoscopy, laparoscopyo Organ biopsieso Dental extractiono Hernia repairo Intramuscular and paravertebral injections

• Majoro Open pelvic, abdominal and thoracic surgeryo Brain surgeryo Major orthopedic and trauma surgeryo Vascular surgery

Beyer‐Westerdorf J, et al. Eur H J 2014:35:1888

Outcome Day 30 after procedure

• Use of bridging increased with severity of surgical procedure

• Cardiovascular events were similar those with bridging (1.6%; 95% CI 0.4‐3.9%) vs

without bridging (0.8%; 95% CI 0.3‐1.9%)

• Major bleeding were more frequent in patients receiving bridging (2.7%; 95% CI 1.1‐5.5%) vs those without bridging (0.5%; 95% CI 0.1‐1.4%) p=0.010


30 Day OutcomesOutcome Procedure Without

Bridging (606)With Bridging (257) p

Major Cardiovascular

MinimalMinorMajorAll

04 (0.7%)1 (0.2%)5 (0.8%)

01 (0.4%)3 (1.2%)4 (1.6%)

>.990.830.0820.265

Major bleeding MinimalMinorMajorAll

02 (0.3%)1 (0.2%)3 (0.5%)

01 (0.4%)6 (2.3%)7 (2.7%)

0.990.6540.0040.010

Any Bleeding MinimalMinorMajorAll

2 (0.3%)21 (0.5%)4 (0.7%)27 (4.5%)

1 (0.4%)8 (3.1%)10 (3.9%)19 (7.4%)

0.6540.730.0010.059


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Perioperative Management of Newer oral Anticoagulants

CrCl T ½ Time of last dose of Dabigatran before procedure

CrCl T1/2 Standard Bleed Risk High Bleed Risk

>80ml/min 14hrs At least 24hrs 48hrs

50‐79ml/min 17hrs At least 24hrs 48‐72hrs

30‐49ml/min 19hrs At least 48hrs 72‐96 hrs

15‐29ml/min 22‐35hrs Not indicated Not indicated

Time of last dose of Apixaban

Standard bleed risk High bleed risk

24hrs 24‐48hrs

Time of last dose of Rivaroxaban

Standard bleed risk High bleed risk

24hrs 24‐48hrs

Preop use of LMWH is not recommended

Perioperative Management of Newer oral Anticoagulants

CrCl(ml/min)

Risk of Bleeding

Rivaroxaban Apixaban Dabigatran Edoxaban

Hold NOAC

≥ 80 LowHigh

≥24≥48

≥ 24≥ 48

≥ 24≥ 48

No data

50‐79 LowHigh

≥ 24≥ 48

≥ 24≥ 48

≥ 36≥ 72

30‐49 LowHigh

≥ 24≥ 48

≥ 24≥ 48

≥ 48≥ 96

15‐29 LowHigh

≥ 36≥ 48

≥ 36≥ 48

Not indicated

≤ 15 Not indicated

Heidbuchel H, et al. Eur Heart J 2013;34:2094Lai A, et al. BJS 2014;101: 742

Restarting NOAC Postoperative

Low Bleeding RiskHigh Bleeding

Risk

Start 24hrs post op Immobile Mobile

LMWH 6‐8hrs postopRestart NOAC 48‐72hrs

Restart NOAC 48‐72hrs

Lai A, et al. BJS 2014;101:742

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Coming Soon

PERIOP 2 ‐ A Safety and Effectiveness Study of LMWH Bridging Therapy Versus Placebo Bridging Therapy for Patients on Long Term Warfarin and Require Temporary Interruption of Their Warfarin.

Tapered Warfarin or Interrupted Warfarin With Heparin Bridging for Pacemaker or Defibrillator Implantation (PACE)

alvin goo- perioperative bridge · 11/3/2015 6 recommendations for major surgery • discontinue...

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