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Perioperative antiplatelet therapymanagement

Dr Borgoens Philippe

Cardiologist

CHR Citadelle Liège

Perioperative antiplatelet therapy management

• 1 000 000 patients undergo coronary stent implantation per year in UE and USA

• 15% and 25% patients undergo invasive or surgical procedurewithin 1 and 5 y post coronary stenting

Urgent surgery

• Surgery required within 48h

• Avoid platelets transfusion 4-6h after thienopyridine and 10-12 h after last intake ticagrelor

Thrombotic risk in elective surgery

Optimal antiplatelet therapy CAD

Optimal antiplatelet therapy PAD

Not only cardiologist point of view…Multidisciplinar approach…

https://itunes.apple.com/us/app/stent-surgery/id551350096?mt=8.

GIHP 2017

Stent <1moStent for MI<6moStent increased ischemic risk <6m

---> HIGH THROMBOTIC RISK

Adapted from GIHP consensus 2017 and Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Hemorrhagic risk and surgery

• LOW: DAPT →continue

• INTERMEDIATE: ASPIRIN →continue

• HIGH: ASPIRIN → stop (very high risk)

Aspirin or P2Y12- monotherapy

Low intermediate high

Primary preventionASA

stop stop stop

Secondaryprevention

ASA or Clopidogrel

continue Continue ASAStop clopidogrel 7d and start ASA

(Stop aspirin 3-5d)Stop clopidogrel 5d+2d if intracranialsurgeryBe carefull si CVA or TIA<1m, CABG<6w

Hemorrhagic risk

Adapted from GIHP consensus 2017

LOW INTERMEDIATE HIGH

LOW AspirinP2Y12-

AspirinP2Y12-

AspirinP2Y12-

INTERMEDIATE AspirinP2Y12-

AspirinP2Y12-

If nondeferrable

AspirinP2Y12-

If nondeferrable(IIbIIIa -?)

HIGH AspirinP2Y12-

(Aspirin)P2Y12-

If nondeferrable

((Aspirin))P2Y12-

If nondeferrable(IIbIIIa -?)

Thrombotic risk

Bleeding

Bitherapy

POSTPONE INTERVENTION IF POSSIBLE

Adapted from GIHP consensus 2017 and Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

ContinueStop

Prasugrel 7d, Clopidogrel 5d, Ticagrelor (3 -5d), ASA 3dIf intracanian surgery: +2 d for all GIHP french consensus 2017

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

Rossini and al, JACC cardiovascular interventions Vol 11 NO S 2018 March 12 2018 4 17-34

• ♂ 75 yo

• PCI DES RCA 3 m ago for ACS

• PCI LAD 5 y ago for stable angina

• GFR 40ml/min

• Diabetes type II

• Asa 100mg od, Brilique 90mg bid

• Acute lithiasic non perforated cholecystis. No septic shock, no migration

Question

1. Stop Brilique 3 d, continue ASA for cholecystectomy

2. Stop Brilique 7 d, continue ASA for cholecystectomy

3. Stop Brilique 5 d, stop ASA 3d for cholecystectomy

4. Continue aspirine and Brilique for cholecystectomy

5. Postpone surgery with antibiotics to at least 1y post ACS

Question

1. Stop Brilique 3 d, continue ASA for cholecystectomy

2. Stop Brilique 7 d, continue ASA for cholecystectomy

3. Stop Brilique 5 d, stop ASA 3d for cholecystectomy

4. Continue aspirine and Brilique for cholecystectomy

5. Postpone surgery with antibiotics to at least 1y post ACS

Complication…

• Choledochal lithiasis migration and acute pancreatitis

-> non deferrable ERCP + sphincterotomy

Question

1. Stop Brilique 3 d, continue ASA

2. Stop Brilique 7 d, continue ASA

3. Stop Brilique 5 d, stop ASA 3d

4. Stop Brilique 3d, stop ASA 3d

5. Stop Brilique 5d, continue ASA

6. Stop Brilique 5d, continue ASA, start IIbIIIa inhibitor

7. Stop Brilique, continue ASA, start LWMH

Questions

1. Stop Brilique 3 d, continue ASA

2. Stop Brilique 7 d, continue ASA

3. Stop Brilique 5 d, stop ASA 3d

4. Stop Brilique 3d, stop ASA 3d

5. Stop Brilique 5d, continue ASA

6. Stop Brilique 5d, continue ASA, start IIbIIIa inhibitor

7. Stop Brilique, continue ASA, start LWMH

Digestive endoscopy

• ♀ 65 yo

• DES LAD for STEMI 2 m ago

• Efient 10mg od, ASA 100mg od

• Discovery malignant brain’s tumor

-> intracranial surgery

Question

1. Stop ASA 5 days and Efient 7 days

2. Continue ASA and stop Efient 7days

3. Stop ASA 7 days, Efient 7 days and bridge LWMH

4. Stop ASA 5 days and Efient 7 days, bridge IIbIIIa inhibitors 3 days before->4h before surgery

Question

1. Stop ASA 5 days and Efient 7 days

2. Continue ASA and stop Efient 7days

3. Stop ASA 7 days, Efient 7 days and bridge LWMH

4. Stop ASA 5 days and Efient 7 days, bridge IIbIIIa inhibitors 3 days before->4h before surgery

Neurosurgery

• ♂68yo

• 2 DES proximal LAD and proximal CX for stable angina 5m ago

• STEMI PCI RCA 5y ago

• LVEF 50%

• Clopidogrel, ASA

• Anemia 9,6gr/l

• Gastroscopy and coloscopy…

Question

1. Stop clopidogrel 5 d continue ASA

2. Stop clopidogrel 7d and stop ASA 3 d

3. Stop ASA 3d, continue clopidogrel

4. Continue clopidogrel and ASA

5. Postpone exams

Question

1. Stop clopidogrel 5 d continue ASA

2. Stop clopidogrel 7d and stop ASA 3 d

3. Stop ASA 3d, continue clopidogrel

4. Continue clopidogrel and ASA

5. Postpone exams

Digestive endoscopy

• ♂68yo

• BMS PTA iliac 2m ago

• Clopidogrel ASA

• Prostatic cancer -> radical prostatectomy

Question

1. Stop clopidogrel 7d and continue ASA

2. Continue clopidogrel ASA

3. Stop clopidogrel 5d and continue ASA

4. Stop clopidogrel 5 d and stop ASA 3d

5. Stop clopidogrel 5d and ASA 5d

6. Stop clopidogrel 5d and ASA 7d

Question

1. Stop clopidogrel 7d and continue ASA

2. Continue clopidogrel ASA

3. Stop clopidogrel 5d and continue ASA

4. Stop clopidogrel 5 d and stop ASA 3d

5. Stop clopidogrel 5d and ASA 5d

6. Stop clopidogrel 5d and ASA 7d

• ♀ 75 yo

• Carotid endarterectomy 1 y ago for stroke and limb amputation 6 m ago

• Clopidogrel 75mg od

• Gastric cancer ->gastrectomy

Question

1. Stop clopidogrel 5d

2. Continue clopidogrel

3. Stop clopidrogel 7d and start aspirin, continue aspirin

4. Stop clopidogrel 7d

Question

1. Stop clopidogrel 5d

2. Continue clopidogrel

3. Stop clopidrogel 7d and start aspirin, continue aspirin

4. Stop clopidogrel 7d

• ♀75 yo

• Stable angina and multivessels disease

• No history MI

• Aspirin

-> CABG

Question

1. Stop ASA 3d

2. Stop ASA 5d

3. Continue ASA

4. Stop ASA 7d

5. Stop ASA 10d

Question

1. Stop ASA 3d

2. Stop ASA 5d

3. Continue ASA

4. Stop ASA 7d

5. Stop ASA 10d

Management of antithrombotic therapy in patients

undergoing elective invasive procedures

Serge Motte

– 21.04.18 -

ANTICOAGULANTS

63

Fondaparinux

DanaparoïdeXa

IIa

TF/VIIa

X IX

IXa

VIIIa

FibrineFibrinogène

AT

Adapté de Weitz & Bates, J Thromb Haemost 2005

Héparines

AT

AT

AVK [II,VII,IX,X]

Rivaroxaban(Xarelto®)

Apixaban(Eliquis®)

Edoxaban(Lixiana®)

Dabigatran(Pradaxa®)

MANAGEMENT OF ANTITHROMBOTIC THERAPY IN PATIENTS

UNDERGOING ELECTIVE INVASIVE PROCEDURES

64

Case 1

76 year-old female

Associated diseases:

Hypertension

Diabetes non-insulin treated

Moderate renal insufficiency (CrCL: 55 ml/min. )

Atrial fibrillation since 10 years, treated with

Sintrom®

Changes in bowel behavior

Planned colonoscopy

MANAGEMENT OF ANTITHROMBOTIC THERAPY IN PATIENTS

UNDERGOING ELECTIVE INVASIVE PROCEDURES

Last intake of Sintrom® on D – 4 and bridging with

therapeutic dose of LMWH

Last intake of Sintrom® on D – 4 and bridging with

prophylactic dose of LMWH

Last intake of Sintrom® on D – 4 and no bridging

Continue Sintrom®, monitor the INR and carry out

the colonoscopy with INR 1,5-2,0

Last intake of Sintrom® on D – 4 and bridging with

therapeutic dose of unfractionated heparin

65

Which option ?

ANTICOAGULANT TREATMENT AND PLANNED INVASIVE PROCEDURES:

WHAT ARE THE RISKS?

66

ANTICOAGULANT TREATMENT AND PLANNED INVASIVE

PROCEDURES: WHAT ARE THE RISKS?

67Rechenmacher SJ et Fang JC. J Am Coll Cardiol 2015;66:1392–403

Periprocedural event rates by oral anticoagulation indication

MANAGEMENT OF AF PATIENTS:

TO BRIDGE OR NOT TO BRIDGE ?

The BRIDGE study: 1884 AF patients

68JD Douketis et al. N Engl J Med. 2015;373:823-33

* P value for non inferiority; † P value for superiority.

BRIDGING RESULTS IN PERIPROCEDURAL BLEEDING WITHOUT

REDUCTION IN THROMBOEMBOLISM

69Rechenmacher SJ et Fang JC. J Am Coll Cardiol 2015;66:1392–403

Periprocedural event rates by bridging strategy

IN CLINICAL PRACTICE

In patients treated with VKAs:

Individualized bridging anticoagulation in specific high-

risk patients with a low bleeding risk procedure

70

WHICH PATIENTS ARE AT HIGH RISK OF THROMBOEMBOLISM

IN CASE OF TEMPORARY INTERRUPTION OF ORAL

ANTICOAGULATION ?

Mechanical mitral heart valve

Multiple mechanical heart valves

Mechanical aortic heart valve and additional risk

factors (history of thromboembolism, AF, heart failure,

dilated cardiomyopathy, intracardiac thrombus)

AF with history of stroke or TIA, left atrial appendage

thrombus

Venous thromboembolism 3 months

71

PROCEDURES CARRYING A HIGH RISK OF BLEEDING

Cardia surgery, major vascular surgery

Neurosurgery

Major surgery for cancer

Urology surgery: prostatectomy, nephrostomy,

nephrectomy, cystectomy

Colonoscopy with polypectomy

Endoscopic sphincterotomy

Vitrectomy, blepharoplasty,..

72

EXAMPLE OF ALGORITHM FOR THE MANAGEMENT OF

SINTROM®

73

High risk of thromboembolism?

Last intake of Sintrom® on D – 4

Yes

No bridging

No

Start Clexane when INR < 2**

Last dose 24 h

before procedure

Yes No

ClCR < 30 ml/min*

Start UFH when INR < 2**

Stop 6 h before procedure

** In practice, start D - 2

Clexane 1 mg/kg/12h; UFH iv , 15 UI/kg/h (no bolus)

EXAMPLE OF ALGORITHM FOR THE MANAGEMENT OF

SINTROM®

74

High risk of thromboembolism ?

After the procédure

Yes

No bridging

No

Start Sintrom J0 ou

later post-procédure

according to

bleeding risk

High risk of bleeding ?

Yes No

No Clexane or UFH

Start Sintrom J1 post-procedure

or later according to bleeding risk

Start Clexane SC 24 h ou

UFH IV 12 h after procedure*

Start Sintrom J0 or

J1 post-procedure

* Clexane 1 mg/kg/12 h

iv UFH : pre-op maintenance dose (no bolus)

MANAGEMENT OF ANTITHROMBOTIC THERAPY IN

PATIENTS UNDERGOING ELECTIVE INVASIVE PROCEDURES

Case 2

72 year-old male

Associated diseases:

Hypertension

Obesity (BMI 33 kg/m2)

Urinary catheter recently placed for acute urinary retention

Planned open surgery for large benign prostate adenoma

Diagnosis of proximal DVP, 2 weeks ago, treatmentwith Xarelto®

75

MANAGEMENT OF ANTITHROMBOTIC THERAPY IN PATIENTS

UNDERGOING ELECTIVE INVASIVE PROCEDURES

Last intake of Xarelto® on D – 3 and bridging with

therapeutic dose of LMWH

Last intake of Xarelto® on D – 3 and bridging with

prophylactic dose of LMWH

Last intake of Xarelto® on D – 3 and no bridging

Postpone surgery up to 3 months of anticoagulant

therapy

76

Which option ?

DIRECT ORAL ANTICOAGULANTS

MAIN PHARMACOKINETIC CHARACTERISTICS

77

CharacteristicsDabigatran

(Pradaxa®)

Rivaroxaban

(Xarelto®)

Apixaban

(Eliquis®)

Edoxaban

(Lixiana®)

T Cmax (h) 2 2-4 1-4 1-2

Half-life 14 à 17 h 7 à 13 h 10 à 14 h 9 à 11h

Renal elimination 80% 35% 27% 50%

EXAMPLE OF ALGORITHM FOR THE MANAGEMENT OF

PRADAXA® (DABIGATRAN)

78

Yes No

Restart 48 h-72 h after procedure

according to bleeding riskRestart 24 h after procedure

Last intake before procedure according ClCR

> 80 ml/min: 3 days 50 - 80 ml/min: 3 - 4 days > 30 - 50 ml/min: 5 days

Last intake before procedure according ClCR

> 80 ml/min: 2 days50 - 80 ml/min: 2 - 3 days > 30 - 50 ml/min: 3 - 4 day

High risk of bleeding ?

79

Yes No

Restart Anti-Xa 48 h-72 h after

procedure according to bleeding riskRestart Anti-Xa 24 h after procedure

Last intake 72 h before procedure Last intake 48 h before procedure

High risk of bleeding or

age > 75 years or ClCR < 50 ml/min ?

EXAMPLE OF ALGORITHM FOR THE MANAGEMENT OF

XA INHIBITORS

CONCLUSIONS 1

80

Periprocedural anticoagulation management often

leads to significant adverse events Bleeding is much more common than clotting

Bridging in patients treated with VKAs results in

periprocedural bleeding without reduction in

thromboembolism

80

CONCLUSIONS 2

In patients treated with VKAs:

Individualized bridging anticoagulation in specific high-risk

patients with a low bleeding risk procedure

In patients treated with DOACs:

No bridging unless oral anticoagulation resumption is

delayed after the procedure

81