Diapositiva 1

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Incidence of surgery after DES
2

• 695 surgeries in 481 patients out of 12.794 with
  DES implantation (5.4)
• Incidence as a function of time
  from intervention

3
Types of intervention
4
In 15 of 36 patients (42) the event
occurred right before or right after a surgical
procedure for which the 2 antiplatelet agents or
Plavix alone was discontinued.
5
Timing of noncardiac surgery in
cardiac-stable/ asymptomatic patients with prior
PCI
2009 ESC Guidelines on perioperative evaluation
for noncardiac surgery
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Risk factors for stent thrombosis
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Additional risk factors for stent thrombosis
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Early surgery after stent implantation risk
stratification for bleeding
Colorectal surgery
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Risk factors for bleeding
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21009 patients , 437 (2.1) with stent thrombosis
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Risk of early surgery after stent implantation

All MACEs were fatal
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Early surgery after stent implantation High risk
after discontinuation of dual antiplatelet therapy
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550 patients undergoing non-cardiac surgery
after stent implantation
35
15
13
9
6
MACE death,MI,stent thrombosis,repeat
revascularization
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Noncardiac surgery after stent implantation Antip
latelet therapy and risk of bleeding
550 patients undergoing non-cardiac surgery
after stent implantation
Van Kuijk P. Am J Cardiol 20091041229
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Early surgery after stent implantation Decision
making
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Ospedali Niguarda e Legnano

• PROTOCOLLO PER LA SOSPENSIONE TEMPORANEA DI
  CLOPIDOGREL PER CHIRURGIA NON-CARDIACA
  INDIFFERIBILE IN PAZIENTI PORTATORI DI STENT
  CORONARICO

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Clopidogrel bridging protocol Inclusion criteria

• Consecutive candidates for urgent major (CV or
  non-CV) surgery
• or eye surgery in whom dual antiplatelet therapy
  could not be withdrawn as the time of surgery was
  within 6 months of the placement of any DES, or
  within one year of the placement of any DES under
  conditions considered to be at higher risk for
  stent thrombosis
• stent implantation due to an ACS,
• diabetes,
• renal insufficiency or
• severe left ventricular dysfunction,
• stents placed in LMCA, proximal LAD (or
  equivalent), bifurcation

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Phase 2 bridge study for urgent surgery early
after DES
Exclusion criteria
Inclusion criteria

• 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

Allergy to tirofiban eptifibatide
Thrombocytopenia lt100.000 Stroke lt 30 days or
prior ICH Intracranial disease Uncontrolled
hypertension Unable to sign consent form
Patients within 6-12 months of DES implantation
high-risk for surgical bleeding, so that the
surgeon would not operate on clopidogrel
surgery
Stop Plavix
Start bridge
Stop bridge
Resume Bridge
Resume Plavix 30075 mg

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

T
Day -5 -4 -3 -2 -1
4h 0 4h
follow-up
until discharge
8h in pts with eGFR lt30 ml/min
if oral admin not possible
as soon as oral admin possible
Primary EP the composite of Death, MI, stent
thrombosis, haemostatic reoperation
Savonitto S et al, Br J Anaesth. 2010 Jan 3.
Epub ahead of print
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Antagonisti della Gp IIb/IIIa farmacocinetica
100
Tirofiban
Abciximab
80
Eptifibatide
60
aggregazione piastrinica
40
20
0
6
12
18
24
30
36
ore dalla sospensione dellinfusione
Mousa et al. Drugs Future 199621 1141-54
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Initial experience 30 patients- 8 cardiac
surgery, 6 urinary tract , 10






gastroenteric surgery, 5 other
surgery - No MACE ( death, MI, stroke )- 1
TIMI major bleeding- 8 patients required blood
transfusion ( 6 before surgery for anemia, 2
post-operatively for proctorrhagy ).
Savonitto S et al, Br J Anaesth. 2010 Jan 3.
Epub ahead of print
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Summary of first 40 cases
Surgical category Type of surgery DES-surgery delay (median,range) Tirofiban pre-op Tirofiban post-op Primary EP (CI 95 0-8.8) Bleeding (TIMI criteria)
Cardiovasc, N 13 CABG 10, Valvuloplasty1 Aortic aneur 2 3, 1-10 months 13 4 0 1 minor bleed 3 transfusion
Urologic N 6 Kidney K 2 Prostate K2 Bladder K2 3, 2-12 months 6 3 0 1 minor bleed 2 transfusion
Abdominal N 14 Gastric K2 Colon K11 Pancreas K1 3, 1-11 months 14 11 0 1 major bleed 1 minor bleed 3 transfusion 1 severe thr.penia
Mixed N 7 Uterus K1 Eye surgery4 Femoral Fr1 Pheocromo1 4, 1-11 months 7 2 0 No bleeding 1 transfusion
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Delay from DES implantation to surgery Updated
October 2, 2009
Median 3 months, range 12 days 12 months
Cardiovascular N 13
Non Cardiovascular N 27
12 months
N 10 17 20 28
29 30 34 36 37 38 39
40
6-12 months N10
lt6 months N30
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Phase 2 bridge study For urgent surgery early
after DES current status
PATIENTS ENROLLED 40 cardiac 13 urinary
tract 6 gastrointestinal 14 mixed surgery
7 PRIMARY ENDPOINT 0 (97.5 C.I.
0-8.81) BLEEDING EVENTS major 1 minor 3 t
ransf. 9 SEVERE THROMBOCITOPENIA 1
The composite of deathMIstent
thrombosishaemostatic reoperation Bleeding
according to TIMI criteria major means Hb
decrease gt5 g/dL, minor means Hb decrease gt3 but
lt5 g/dL, after correction for transfusion (1 g
ofHb for each U transfused) platelet count
lt20,000.
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550 patients undergoing non-cardiac surgery
after stent implantation
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14
4
MACE death,MI,stent thrombosis,repeat
revascularization
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Combined events ( death,MI,stent thrombosis as a
function of time )
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695 surgeries in 481 patients out of 12.794 with
DES implantation (5.4)
Incidence as a function of time from intervention
Death , MI , stent thrombosis
Stent thrombosis
Events as stratified by time from PCI to surgery
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Early surgery after stent implantation High risk
after discontinuation of dual antiplatelet therapy
October
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Early surgery after stent implantation risk
stratification for stent thrombosis
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Antagonisti della Gp IIb/IIIa tollerabilità
Studio farmaco
sanguinamenti maggiori (TIMI) p
trattamento placebo
lt0,001 NS 0,043 NS NS lt0,001
EPIC EPILOG CAPTURE EPISTENT IMPACT II PURSUIT
6,6 3,1 1,9 2,2 4,8 1,3
Abciximab Abciximab Abciximab Abciximab Eptifibati
de Eptifibatide
14 2,0 3,8 1,5 5,1 3,0
Lamifiban
0,5 2,4 0,4 1,4
1,5 2,1 0,4 0,8
PARAGON
NS NS NS NS
Tirofiban Tirofiban Tirofiban
RESTORE PRISM PRISM-PLUS
adapted from Blankenship et al. Am Heart J Oct
1999 138 S287-S296
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• F.G. , woman , 77 years old
• Type II diabetes, hypertension
• October 08 , NSTE-ACS
• Coronary arteriography prox LAD 80
• PCI ( Cypher 3-18 )
• Discharged with ASA 75 mg, Plavix 75mg,
• Atorvastatin 20 mg, Metformin 1500 mg,
• Ramipril 10 mg.

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• December 2008 recurrent fever, urine culture
  analysis positive for Escherichia Coli . Treated
  with antibiotics
• January 2009 hospitalized because of abdominal
  pain , colonoscopy colo-vesical fistula .
• Surgery needed ( colon resection, vesical suture
  ).

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• Stent thrombosis is observed in about 2 per cent
  of patients after 1 year of implantation , but
  it results in death in more than 20 of cases and
  in death and MI in nearly 90 of cases.

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• Problems
• Discontinuation of clopidogrel ?
• Surgery on clopidogrel ?

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• Problems
• Discontinuation of clopidogrel ? ( risk of stent
  thrombosis )

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BUT
161 cases of late-very late definite stent
thrombosis published in the literature
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21009 patients , 437 (2.1) with stent thrombosis
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• Problems
• Discontinuation of clopidogrel ? ( risk of stent
  thrombosis )
• Surgery on clopidogrel ? ( surgeons objections
• 1) risk of important bleeding 2) no
  absorption of the drug in the perioperative
  period.

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CF.V. 77 years old- Clopidogrel discontinued 5
days before surgery starting January 31st.-
Tirofiban infusion ( dose used for NSTE-ACS no
heparin )- February 5th surgery ( colon
resection, vesical suture ). Tirofiban resumed
until intestinal canalization ( February 9th when
clopidogrel LD 300 mg and aspirin were given and
Tirofiban discontinued )- No clinical
complications , no major bleeding . Pre-op Hb
10.3g/dl (Transfusion 2U) Hb post-op (February
9th) 10.2g/dl
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Protocollo Ospedale Niguarda
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Patient characteristics and bleedinggastroenteric
surgery
Patient No. Gender Age Stented artery Months after DES, type of DES Reason for PCI Type of surgery diagnosis Tirofiban infusion pre-surgery (hrs) Tirofiban infusion post-surgery (hrs) Bleeding events
1 Male 68 LMCA, LAD 1, Paclitaxel STEMI Hemicolotomy cancer 62 120 No bleeding, 2U RBC pre-operatively
2 Female 78 LAD 12, everolimus Stable angina Hemicolotomy cancer 72 120 No bleeding, no transfusion
3 Male 71 LMCA, LCx, RCA 4, paclitaxel, everolimus NSTEACS Cholecystectomy recurrent cholecystitis 114 48 No bleeding, no transfusion
4 Male 69 LAD, Lcx 8, Paclitaxel Stable angina Pharyngotomy, cancer 111 0 No bleeding, no transfusion
5 Female 72 LAD 1, Paclitaxel NTEACS Hemicolotomy cancer 113 312 No bleeding, no transfusion Reoperation due to occlusion
6 Male 80 LAD 9, Everolimus Stable angina Endoscopic polypectomy, cancer 72 0 No bleeding, no transfusion
7 Male 60 LAD 7, Everolimus STEMI Resection of the rectum, cancer 112 384 No bleeding, no transfusion Reoperation due to occlusion
8 Male 65 RCA 2, Sirolimus NSTEACS Gastrectomy, hemicolotomy, cancer 120 120 No bleeding, no transfusion
9 Female 77 LAD 4, Sirolimus NSTEACS Sigmoid resection, cancer 113 98 No bleeding, no transfusion
10 Male 73 LAD 3, everolimus STEMI Hemicolotomy, cancer 105 94 Major bleeding on 7th post-op day from enterocolic anastomosis. Resolved by operative coloscopy (2 clips). 6 U GRC transfused.
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Patient No. Gender Age Stented artery Months after DES, type of DES Reason for PCI Type of surgery diagnosis Tirofiban infusion pre-surgery (hrs) Tirofiban infusion post-surgery (hrs) Bleeding events
1 Male 68 LMCA, LAD 1, Paclitaxel STEMI Hemicolotomy cancer 62 120 No bleeding, 2U RBC pre-operatively
2 Female 78 LAD 12, everolimus Stable angina Hemicolotomy cancer 72 120 No bleeding, no transfusion
3 Male 71 LMCA, LCx, RCA 4, paclitaxel, everolimus NSTEACS Cholecystectomy recurrent cholecystitis 114 48 No bleeding, no transfusion
4 Male 69 LAD, Lcx 8, Paclitaxel Stable angina Pharyngotomy, cancer 111 0 No bleeding, no transfusion
5 Female 72 LAD 1, Paclitaxel NTEACS Hemicolotomy cancer 113 312 No bleeding, no transfusion Reoperation due to occlusion
6 Male 80 LAD 9, Everolimus Stable angina Endoscopic polypectomy, cancer 72 0 No bleeding, no transfusion
7 Male 60 LAD 7, Everolimus STEMI Resection of the rectum, cancer 112 384 No bleeding, no transfusion Reoperation due to occlusion
8 Male 65 RCA 2, Sirolimus NSTEACS Gastrectomy, hemicolotomy, cancer 120 120 No bleeding, no transfusion
9 Female 77 LAD 4, Sirolimus NSTEACS Sigmoid resection, cancer 113 98 No bleeding, no transfusion
10 Male 73 LAD 3, everolimus STEMI Hemicolotomy, cancer 105 94 Major bleeding on 7th post-op day from enterocolic anastomosis. Resolved by operative coloscopy (2 clips). 6 U GRC transfused.
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Patient characteristics and bleedingurinary
tract surgery
Patient No. Gender Age Stented Artery Months after DES, type of DES Reason for PCI Type of surgery diagnosis Tirofiban infusion pre-surgery (hrs) Tirofiban infusion post-surgery (hrs) Bleeding events
1 Male 56 LMCA, RCA 6, sirolimus Stable angina Bladder surgery cancer 100 0 No bleeding, no transfusion
2 Male 79 LAD 12, sirolimus STEMI Bladder surgery cancer 120 0 No bleeding, no transfusion
3 Male 60 LCx, RCA 3, sirolimus Stable angina Conservative nephrotomy cancer 96 48 No bleeding, no transfusion
4 Male 76 LAD 2, everolimus NSTEACS Conservative nephrotomy cancer 120 48 No bleeding, transfusion of 3U RBC due to proctorrhagia on 6th post-operative day angiodysplasia
5 Male 59 LAD 4, paclitaxel STEMI Endoscopic bladder surgery cancer 114 288 Minor bleeding, transfusion of 4U RBC
6 Male 78 RCA 2, everolimus Stable angina Bladder surgery cancer 120 0 No bleeding, no transfusion
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Patient characteristics and bleeding Cardiac
surgery
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Patient characteristics and bleedingmixed surgery
Patient No. Gender Age Stented artery Months after DES, type of DES Reason for PCI Type of surgery diagnosis Tirofiban infusion pre-surgery (hrs) Tirofiban infusion post-surgery (hrs) Bleeding events
1 Male 48 RCA, LCx 4, paclitaxel Stable angina Vitrectomy and pucker peeling 120 0 No bleeding, no transfusion
2 Male 79 RCA 2, sirolimus Stable angina Femoral fracture 112 0 No bleeding, 1U of GRC post-surgically
3 Female 74 LCx, RCA 7, sirolimus NSTEACS Hysterotomy, cancer 120 24 No bleeding, no transfusion
4 Male 60 LCx 11, sirolimus Stable angina Vitrectomy 120 0 No bleeding, no transfusion
5 Female 76 LAD 5, everolimus NSTEACS Femoral fracture 112 0 No bleeding, no transfusion
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Delay from DES implantation to surgery Updated
October 2, 2009
Median 3 months, range 12 days 12 months
Cardiovascular N 13
Non Cardiovascular N 27
12 months
Cumulative N 10 17 20 28 29
30 34 36 37 38 39 40
6-12 months N10
lt6 months N30
Savonitto S. Br J Anaesth , in press
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141 Patients 7.6 3 months after DES implantation
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141 Patients 7.6 3 months after DES implantation
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Clopidogrel bridging protocol Exclusion criteria
Pazienti con nota allergia a precedente
somministrazione di tirofiban Piastrinopenia
lt100.000 x 10-9/L storia di ictus nei 30 giorni
precedenti o anamnesi di ictus emorragico
anamnesi positiva per patologie intracraniche
(neoplasie, malformazioni arterovenose,
aneurismi) storia di diatesi emorragica
ipertensione grave (PAS gt 200 mm Hg o PAD gt 110
mm Hg nonostante il trattamento
antiipertensivo) Pazienti non consenzienti o
non in grado di firmare il consenso informato.
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Early surgery after stent implantation risk
stratification for stent thrombosis
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Early surgery after stent implantation risk
stratification for consequences of stent
thrombosis
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Early surgery after stent implantation Decision
making
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Early surgery after stent implantation risk
stratification for stent thrombosis
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Early surgery after stent implantation Prevention
strategies
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Early surgery after stent implantation risk
stratification for bleeding and thrombosis
Chassot PJ, BJA 2007
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Early surgery after stent implantation Continuati
on of antiplatelet therapy
Chassot PJ, BJA 2007
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Incidence of urgent surgery after DES
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Perioperative stent thrombosis
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437 stent thrombosis (152 DES Mean follow-up
30.9 months)
N140 (32)
N180 (41)
N36 (8)
N22 (5)
N59 (14)
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