IV CONVENTION UTIC LOMBARDE 8-9 Aprile 2011

Gestione del rischio emorragico nella chirurgia non cardiaca maggiore

Maria Rosa ConteOspedale Mauriziano -Torino

Guidelines for pre-operative cardiac riskassessment and perioperative cardiacmanagement in non-cardiac surgery

The Task Force for Preoperative Cardiac Risk Assessment andPerioperative Cardiac Management in Non-cardiac Surgery of the

European Society of Cardiology (ESC) and endorsed by theEuropean Society of Anaesthesiology (ESA)

Change in numbers of discharges for surgical procedures by age for the time periods 1994/95 and 2004/05 as reported from the 2005 US National Hospital Discharge Survey (non-federal short-stayhospitals)

Age (years) Number of procedures(in thousands) % change

1994/95 2004/0518–44 7311 7326 + 2.145–64 4111 5210 + 26.765–74 3069 3036 - 1.175 and over 3479 4317 + 24.118 and over 17969 19889 + 10.74317 þ24.1969 19 889 þ10.7

Impact of the ageing population

Within the next 20 years, the acceleration in ageing of the populationwill have a major impact on perioperative patient management.It is estimated that elderly people require surgery four times more often than the rest of the population. Although exact data regarding the number of patients undergoing surgeryin Europe are lacking, it is estimated that this number will increase by 25% by 2020, and for the same time period the elderly population will increase by .50%. The total number of surgical procedures will increase even faster because of the rising frequency of interventions with age.

10-

8-

6-

4-

2-

0-

AustrianVicenzi MNBJA 2006

Incidence of surgery within 1 year after coronary stenting

ClevelandAnwaruddin S

JACC Intv 2009

3.8%5.0%

8.6%

New ZealandTo ACY

Circ CV Intv 2009

NoncardiacCardiac (20%)+ Noncardiac

Noncardiac

4.4%

ScottishCruden N

Circ CV Int 2010

Noncardiac

4.4%major

EVENTREGISTRY

Berger PBJACC Intv 2010

Noncardiac

2.0%minor

10-

8-

6-

4-

2-

0-

4.4

AustrianN=2000

ScottishN=1,953

ClevelandN=12,794

3.8

5.0

Cardiovascular death

Myocardial Infarction

CNR-OD 1 studyEvents per year (%)

1083 pts with stable CAD followed for 66+11 months,

pre-PCI era

Brunelli C. Eur Heart J 1989

1.01.5

Incidence of surgery first yearafter stent (%)

In patients with stable CAD, Probability of surgery higher than probability of D+MI

10-

8-

6-

4-

2-

0-

8.6

New Zealand

Vicenzi MN. BJA 2006; Anwaruddin S. JACC Intv 2009 Cruden N. Circ CV Int 2010; To ACY. Circ CV Interv 2009

Patients caratheristics

11150 patients (age, 62+-11 years;30% women) who underwent PCI from 1996 to 2001 (New Zealand), 5-year follow-up: 26% of the population underwent at least 1 noncardiac surgical procedure

(23% orthopedic, 20% abdominal, 12% urologic, 10% vascular, 35% others)

Circ Cardiovasc Intervent. 2009;2:213-221.

The main clinical predictors of noncardiac surgery were advanced age, previous noncardiac surgery, osteoarthritis, and peripheral vascular disease.

Noncardiac surgery is required frequently after PCI, whereas bleeding is less common. Before implanting a drug-eluting or bare-metal stent, individual patient risk stratification by the interventional cardiologist should include assessment of whether there is an increased likelihood of needing noncardiac surgery or developing bleeding.

Clinical presentation at the time of PCI

Patients undergoing noncardiac surgery after recent coronary stent implantation are at increased risk of perioperative myocardial ischemia, myocardial infarction, and death, particularly after an acute coronary syndrome. For at least 2 years after percutaneous coronary intervention, cardiac outcomes after noncardiac surgery are similar for both drug-eluting and bare-metal stents.

Perioperative death and ischemic cardiac events occurred more frequently when surgery was in patients revascularized after an acute coronary syndrome (65% versus 32% - elective indication - ; P=0.037).

(acute coronary syndrome [triangles] vs stable coronary artery disease [diamonds])

% o

f S

ubje

cts

2.31%

DAYS0

0.5

1

1.5

2

2.5

0 50 100 150 200 250 300 350 400 450

Clopidogrel-treated patients

2.41%

DAYS0

0.5

1

1.5

2

2.5

0 50 100 150 200 250 300 350 400 450

Definite/Probable ST: DES Only (N=5743)

Definite/Probable ST: BMS Only (N=6461)

Wiviott SD. Lancet 2008;371:1353

Time course and incidence of ST after a NSTEACSDoes not differ between BMS and DES

Clopidogrel-treated patients

TIMING

Scottish Coronary Revascularisation Register

From April 2003 and March 2007,1953 post-PCI patients underwent noncardiac surgery. Of these, 570 (29%) were treated with at least 1 drug-eluting stent and 1383 (71%) with bare-metal stents only.

Circ Cardiovasc Interv. 2010;3:236-242.)

2009 ESC Guidelines on perioperative evaluation for noncardiac surgery

Timing of noncardiac surgery in cardiac-stable/asymptomatic patients with prior PCI

Guidelines for pre-operative cardiacmanagement in non-cRecommendations on timing of non-cardiac surgery incardiac-stable/asymptomatic patients with prior revascularization

Recommendations Class Level It is recommended that patients withprevious CABG in the last 5 years be sent I Cfor non-cardiac surgery without furtherdelay

It is recommended that non-cardiac surgerybe performed in patients with recent bare I Bmetal stent implantation after a minimum 6weeks and optimally 3 months followingthe intervention

It is recommended that non-cardiac surgerybe performed in patients with recent I Bdrug-eluting stent implantation nosooner than 12 months following theintervention

Consideration should be given to postponingnon-cardiac surgery in patients with recent II a Bballoon angioplasty until at least 2 weeksfollowing the intervention

DAT MANAGEMENT

Class I

Class IIb

Occurrence of early andlate angiographically-documentedstent thrombosis in the Rotterdam andBern registries

Daemen J, Lancet 2007;369:667

Independent predictors HR 95%CIACS at presentation 2.3 1.3-4.0

Diabetes 2.0 1.1-3.8

30D 3y

0.6% per year

Predictors of stent thrombosis the dutch registry: 437 out of 21,009 pts (2.1%)

Van Werkum JW. JACC 2009;53:1399

Schulz S. Eur Heart J 2009;30:2714

Clopidogrel discontinuation and incidence of stent thrombosis after PCI in the ISAR studies

Cumulative incidence of stent thrombosis in patients who continued (black) and those who discontinued clopidogrel (red).

Patients switched from one group to the otheras soon as they stopped taking clopidogrel.

Clinical outcome of stent thrombosis At 30-day and 180-day follow-up

Airoldi F. Circulation 2007;116:745-54

NCS after percutaneous coronary intervention

•Stent Thrombosis risk

•Timing dell’impianto Stent

•SCA o coronaropatia stabile

•Tipo di STENT

•Diabete

•Lunghezza dello Stent

•Biforcazioni / lesioni ostiali…

•BLEEDING RISK

•Female sex

•Diabetes, Chronic renal impairment

• bleeding……

SURGICAL RISK

•Ch aortica e vascolare maggiore

BLEEDING SURGICAL RISK

intracranial

spinal

Extraocular

TURP

RISCHIO EMORRAGICORISCHIO EMORRAGICO

CatarattaTrabeculectomiaGlaucoma

BassoBasso

Chirurgia complessa su retina

Chirurgia complessa su palpebra

Chirurgia complessa su ghiandole lacrimali

Chirurgia complessa a livello orbitario

con necessità di anestesia retro bulbare

IntermedioIntermedio

IntermedioIntermedio

IntermedioIntermedio

AltoAlto

RISCHIO EMORRAGICORISCHIO EMORRAGICOCHIRURGIA OCULARECHIRURGIA OCULARE

Ickx et al. Can J Anesth 2006; 53: 6; S113-22Thachil J. et al. British Journal of Surgery 2008; 95: 1437–1448.

RISCHIO EMORRAGICORISCHIO EMORRAGICO

Cistoscopia BassoBasso

Litotrissia

Biopsia prostatica

Biopsia renale

IntermedioIntermedio

AltoAlto

AltoAlto

RISCHIO EMORRAGICORISCHIO EMORRAGICOPROCEDURE UROLOGICHEPROCEDURE UROLOGICHE

Ickx et al. Can J Anesth 2006; 53: 6; S113-22Thachil J. et al. British Journal of Surgery 2008; 95: 1437–1448.

Recommendation/statement on surgical risk estimate

Recommendation/statement Class Level

Laparoscopic procedures demonstrate a cardiac

stress similar to open procedures and it is I A

recommended that patients be screened prior

to intervention accordingly

RISCHIO EMORRAGICORISCHIO EMORRAGICO

del tratto gastrointestinale superioredel tratto gastrointestinale inferioreERCP senza sfinterectomiaInserzione di stent biliare senza sfinterectomiaEndosonografia senza incannulazioneEnteroscopia “push” dell’intestino tenueCapsula endoscopica

con o senza biopsia BassoBasso<1%<1%

PolipectomiaCoagulazione laserSfinterectomia endoscopicaDilatazione pneumaticaStenting esofageoPosizionamento di PEGTrattamento di variciERCP con sfinterectomiaResezione della mucosa o dissezione sub mucosa per via endoscopicaEndoscopia ad ultrasuoni con ago aspirato

AltoAlto≥≥1%1%

RISCHIO EMORRAGICORISCHIO EMORRAGICOPROCEDURE ENDOSCOPICHE GASTROINTESTINALI (GI)PROCEDURE ENDOSCOPICHE GASTROINTESTINALI (GI)

Ickx et al. Can J Anesth 2006; 53: 6; S113-22Thachil J. et al. British Journal of Surgery 2008; 95: 1437–1448.Kwok A. et al. Am J Gastroenterol online pubblication, 11 August 2009; doi:10.1038/ajg.2009.469

How to manage post-stent DAT & NCS?

British Journal of Anaesthesia 105 (S1): i3–i15 (2010)

Relative contributions of key hazards associated with major adverse cardiovascular events in patients with coronary stents. These form the framework for clinical decision-making.

Van Kuijk P. Am J Cardiol 2009;104:1229

Noncardiac surgery after stent implantation:Antiplatelet therapy and risk of bleeding

Clopidogrel was discontinued 5 days before surgery, and hospital admission was planned for the day after the last clopidogrel intake (4 days before surgery), when i.v. tirofiban infusion was started according to the schedule approved for patients with ACS: that is, 0.4 mg kg21 min21 over 30 min, followed by 0.1 mg kg21 min21.15 The tirofiban dose was reduced by 50% if creatinine clearance was ,30 ml min21. The infusion was stopped 4 h before surgery (8 h in the case of creatinine clearance ,30 ml min21), resumed at the same schedule (including the 30 min bolus) 2 h after the end of surgery, and continued for up to 6 h after the resumption of clopidogrel, unless oral administration could be resumed on the same day as surgery. After surgery, clopidogrel was reintroduced using a loading dose of 300 mg (four tablets) as soon as the patient could resume oral administration, and then continued at a once daily dose of 75 mg. Aspirin (75–100 mg once a day) was ideally to be continued throughout the perioperative period

Results: There were no cases of death, myocardial infarction, stent thrombosis, or surgical re-exploration due to bleeding during the index admission, with a risk estimate of 0–11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial infarction (TIMI) major and one of TIMI minor bleeding in the postoperative phase; another four patients were transfused without meeting the TIMI criteria for major or minor bleeding.

Br J Anaesth 2010; 104: 285–91

surgery

Day -5 -4 -3 -2 -1 4h* 0 4h follow-up until discharge

Stop PlavixStop Plavix

StartbridgeStart

bridge

*8h in pts with eGFR <30 ml/min

StopbridgeStop

bridge

T

ResumeBridge**Resume

Bridge**Resume

Plavix 300+75 mg***Resume

Plavix 300+75 mg***

**if oral adminnot possible

*** as soon as oral admin possible

Phase 2 protocol (Simon’s two stage design)for urgent surgery early after DES

Primary EP: the composite ofDeath, MI, stent thrombosis, haemostatic reoperation

12 months in the case of high-risk of ST:•stent implantation due to an ACS•diabetes•renal insufficiency •severe LV dysfunction •DES in LMCA, proximal LAD, bifurcation

Exclusion criteria

· Allergy to tirofiban – eptifibatide

· Thrombocytopenia <100.000

· Stroke < 30 days or prior ICH

· Intracranial disease

· Uncontrolled hypertension

· Unable to sign consent form

Inclusion criteria

Patients within 6-12 monthsof DES implantation

+high-risk for surgical bleeding,

“so that the surgeon would not operate on clopidogrel”

•Aspirin continued throughout•Low-dose LMWH for DVT prevention•Aspirin continued throughout•Low-dose LMWH for DVT prevention

Savonitto S. Br J Anaesth 2010;104:285-91

Phase 2 bridge studyFor urgent surgery early after DES: current status

PATIENTS ENROLLED 56cardiac 19urinary tract 7gastrointestinal 18mixed surgery 12

PRIMARY ENDPOINT* 0 (97.5% C.I. 6.4%)

BLEEDING** EVENTS major 2 minor 3 transf 12

SEVERE§ THROMBOCITOPENIA 1

* The composite of death+MI+stent thrombosis+haemostatic reoperation**Bleeding according to TIMI criteria: major means Hb decrease >5 g/dL,minor means Hb decrease >3 but <5 g/dL, after correction for transfusion(1 g ofHb for each U transfused); § platelet count <20,000.

Urgent surgery after DES.. Savonitto De Servi

Early surgery after stent implantation:Anesthesiologist warning

Heart, Lung and Circulation 2010;19:2–10

CONCLUSIONI I • con l’ aumentare dell’eta’ un crescente numero di pazienti va

incontro ad interventi di chirurgia non cardiaca

• al momento dell’impianto di uno Stent (che richiede una DAPT da un

minimo di 1 mese ad un massimo di 12-15 mesi ) devono essere considerati con attenzione il rischio emorragico ed le patologie associate

• la trombosi di Stent è un evento drammatico con elevata mortalità ed è principalmente determinato dalla interruzione prematura della DAPT

• Nei pazienti portatori di Stent coronarici l’intervento chirurgico dovrebbe essere differito a 3 mesi in caso di BMS e 12 mesi in caso di DES

• In caso di intervento non differibile ad elevato rischio emorragico in pazienti con elevato rischio trombotico la bridge strategy con agenti antipiastrinici ev a breve durata d’azione si e’ dimostrata efficace nella prevenzione della ST senza aumentare significativamentel e emorragie.

• l’impiego di tale strategia e’ tuttavia ancora controverso e non indicato dalle linee guida con livello elevato di evidenza

• Nei pazienti con eccessivo sanguinamento peri-operatorio sono indicati trasfusioni di piastrine e agenti pro emostatici

• Nuovi farmaci quali il Ticagrelor ( breve emivita ) potrebbero in futuro costituire un alternativa all’impiego degli inibitori del II b- III a ( piccole molecole ).

Gurbel P. Circulation 2009, published online Nov 19

Ticagrelor vs clopidogrel: time course of IPA by 20 M/L ADP

Reversibility of platelet inhibition

Oral drug aspirin clopidogrel prasugrel ticagrelor

Reversibilityirreversible

irreversible irreversible reversible

Time to surgery

5-7 days 5-7 days 5-7 days 3 days?

i.v. drug abciximab tirofiban eptifibatide

Reversibility irreversible reversible reversible

Time to surgery

3-5 days 4 hours(8 hours if CrCl <30 ml)

4 hours

Kwok A. et al. Am J Gastroenterol online pubblication, 11 August 2009; doi:10.1038/ajg.2009.469

GESTIONE ANTIAGGREGANTIGESTIONE ANTIAGGREGANTIIN PROCEDURE ENDOSCOPICHE GIIN PROCEDURE ENDOSCOPICHE GI

Healthy volunteer crossover study IPA (20 M ADP) at 24 hours

Brandt J et al. AHJ 2006Brandt J et al. AHJ 2006

––2020

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Response to Response to prasugrelprasugrel

60 mg60 mg

Response to Response to clopidogrel 300 mgclopidogrel 300 mg

N=64N=64

Gum PA et al. Am J Cardiol 2001;88:230-235

ASA-R: mean aggregation ASA-R: mean aggregation ≥70% with µM 10 ADP & ≥70% with µM 10 ADP & ≥20% with 0.5 mg/ml AA ≥20% with 0.5 mg/ml AA

325 patients with stable CVD taking ASA 325 mg >7days325 patients with stable CVD taking ASA 325 mg >7days

Prevalence of ASA Resistance

Biondi-Zoccai GGL, et al. Eur Heart J 2006 27:2667-2674

La sospensione degli Antiaggreganti Sospensione ASA in 50.279 coronaropatici

Aumentato Rischio Trombotico

SEMIN CARDIOTHORAC VASC ANESTH 2010 14: 256

Conclusions on DAPT and surgical risk

• For surgical and endoscopic procedures at HR of bleeding, DAPT

represents a serious issue.

• Withdrawal of DAPT + post-surgical haemostatic activation + malignancy

increase severalfold the risk of ST and death, THE POST-OPERATIVE

FASE BEING THE MORE DANGEROUS.

• Based on the results of our ongoing experience, we propose that a “bridge

strategy” using short-acting i.v. antiplatelet agents confers protection

against perioperative CV events that goes beyond the prevention of ST,

without increasing the risk of surgical bleeding.

• Among the new P2Y12 antagonist, the reversible blocker ticagrelor might

reduce by 1-2 days the duration of pre- operative withdrawal, but it’s use in

the early post-op days should be studied, and sofar it hasn’t been shown to

reduce bleeding compared to clopidogrel.

• The concept of “platelet anaesthesia” should be further explored

Early surgery after stent implantation:Step 2: risk stratification for stent thrombosis

Heart, Lung and Circulation 2010;19:2–10

• Tutti gli stent coronarici richiedono un periodo di DAPT post-impianto: 4 settimane i BMS, 6-12 mesi i DES. Ciò al fine di prevenire la trombosi di stent (morte-infarto nel 50-70% dei casi)

• La terapia antiaggregante aumenta il rischio emorragico in chirurgia generale, laparoscopica, e durante procedure endoscopiche

• La sospensione della terapia antiaggregante prima che sia finito il periodo di vulnerabilità espone al rischio di trombosi di stent, aumentato dall’ effetto pro-trombotico della chirurgia

Pazienti con STENT coronariciche devono essere sottoposti a chirurgia non cardiaca

surgery, either elective or urgent, poses a largely unsolved problem for patients on dual antiplatelet therapy and their treating physicians.

Schulz S. Eur Heart J 2009;30:2714