1. Dr. Dev PahlajaniDr. Dev Pahlajani
MD,FACC,FSCAIMD,FACC,FSCAI
ANTICOAGULATION IN
COMPLEX PCI
Chief of Interventional cardiology
Breach Candy Hospital and Consultant Cardiologist
Nanavati Heart Institute,Mumbai

2. Anticoagulation in complex PCI
STEMI,NSTEMI
COMPLEX ANATOMY
CTO,BIF.MULTIPLE STENTS
NEED FOR DAPT+OAC
PROSTHETIC VALVE
AFIB,LV THROMBUS +TIA

3. Major Bleeding is Associated with an Increased
Risk of Hospital Death in ACS Patients
Moscucci et al.Moscucci et al. Eur Heart JEur Heart J 2003;24:1815-232003;24:1815-23
GRACE Registry in 24,045 ACS patientsGRACE Registry in 24,045 ACS patients
*After adjustment for comorbidities, clinical presentation and hospital therapies*After adjustment for comorbidities, clinical presentation and hospital therapies
**p<0.001 for differences in unadjusted death rates**p<0.001 for differences in unadjusted death rates
OR (95% CI)OR (95% CI)
1.64 (1.18 to 2.28*)1.64 (1.18 to 2.28*)
00
Overall ACSOverall ACS UAUA NSTEMINSTEMI STEMISTEMI
1010
2020
3030
4040
****
**** ****
****
5.15.1
18.618.6
3.03.0
16.116.1
5.35.3
15.315.3
7.07.0
22.822.8
Inhospitaldeath(%)Inhospitaldeath(%)
In hospital major bleedingIn hospital major bleeding YesYesNoNo

4. Blood Transfusion is Associated with
an Increased 30-Day Mortality in NSTEMI
Rao et al.Rao et al. JAMAJAMA 2004;292:1555-622004;292:1555-62
N=24,112 ACS patients from GUSTO IIb, PURSUIT and PARAGONN=24,112 ACS patients from GUSTO IIb, PURSUIT and PARAGON
*Adjusted for baseline characteristics, bleeding and transfusion propensity and nadir hematocrit*Adjusted for baseline characteristics, bleeding and transfusion propensity and nadir hematocrit
HR=3.94*;HR=3.94*;
95%CI: 3.26 to 4.7595%CI: 3.26 to 4.75
30-day30-day
death ratedeath rate
TransfusionTransfusion
No TransfusionNo Transfusion
Log-rankLog-rank p<0.001p<0.001
00
0.020.02
0.040.04
0.060.06
0.080.08
0.100.10
55 1010 1515 2020 2525 3030
DayDay
8.00%8.00%
3.08%3.08%
CumulativemortalityCumulativemortality

5. Potential Mechanisms for the Higher
Morbidity/Mortality Associated with Bleeding
1. Cessation of antithrombotic therapies after bleeding may
increase subsequent ischemic events
2. Patients who bleed may have an heightened
inflammatory state
3. Adverse effects of hypotension
4. Adverse effects of transfusion
5. Common risk factors for bleeding and adverse outcome
1. Gibbons & Fuster. N Engl J Med 2006;354:1524-7
2. Califf. JAMA 2006;295:1579-80
3. Jozic J. AJC 2006;98:36M

6. Sweet spot for P2Y12 inhibition
M.Valgimigli, EUROPCR, 2013

7. Plethora of choices for Antithrombotic therapy
• Anticoagulants: UFH LMWH Fonda Bival
• Antiplatelets: ASA Clopidogrel (dose) Prasugrel (dose) Ticagrelor
• IV antiplatelets : None AbcixEpt/ Tiro (timing)
• Oral anticoagulant None Rivaroraban

8. Anticoagulation strategies in
complex PCI
OAC WITH ?
DAPT? TOAT? SAPT
PPCI BIVALURIDIN,LMWH

9. Primary Outcome Measures (ITT)Primary Outcome Measures (ITT)
12.1
8.3
5.5
9.2
4.9 5.4
0
5
10
15
20
Net adverse clinical
events
Major bleeding* MACE**
30dayeventrates(%)
Heparin + GPIIb/IIIa inhibitor (N=1802) Bivalirudin monotherapy (N=1800)
RR = 0.99 [0.76, 1.30]RR = 0.99 [0.76, 1.30]
PPsupsup = 0.95= 0.95
RR = 0.60 [0.46, 0.77]RR = 0.60 [0.46, 0.77]
PPsupsup ≤ 0.0001≤ 0.0001
RR = 0.76 [0.63, 0.92]RR = 0.76 [0.63, 0.92]
PPsupsup = 0.005= 0.005
1° endpoint 1° endpoint
*Not related to CABG*Not related to CABG
**MACE = All cause death, reinfarction,**MACE = All cause death, reinfarction,
ischemic TVR or strokeischemic TVR or strokeStone GW, et al.Stone GW, et al. N Engl J MedN Engl J Med. 2008 May 22;358(21):2218-30. 2008 May 22;358(21):2218-30

10. HORIZONS AMI—30-Day Stent
Thrombosis (N=3,124)
UFH + GP IIb/IIIaUFH + GP IIb/IIIa
(N=1553)(N=1553)
BivalirudinBivalirudin
(N=1571)(N=1571)
PP
ValueValue
ARC definite orARC definite or
probable*probable*
1.9%1.9% 2.5%2.5% 0.330.33
DefiniteDefinite 1.4%1.4% 2.2%2.2% 0.110.11
ProbableProbable 0.5%0.5% 0.3%0.3% 0.260.26
AcuteAcute
(≤24 hrs)(≤24 hrs)
0.3%0.3% 1.3%1.3% 0.00090.0009
SubacuteSubacute
(>24 hrs – 30d)(>24 hrs – 30d)
1.7%1.7% 1.2%1.2% 0.300.30
Stone GW, et al. N Engl J Med. 2008 May 22;358(21):2218-30

11. WHY IS THERE AN EXCESS OF EARLY
STENT THROMBOSIS IN HORIZONS AMI ?
Clopidogrel
BIVALIRUDIN
ASPIRIN
PPCI 24hrs

12. Bivalirudin plasma levels in PCI
• Plasma concentrations vs time(25 min elimination half life)
• Bolus plus infusion (for the duration of the procedure) is
required dosing

13. HORIZONS:
Impact of pre-randomized heparin on Acute Stent
Thrombosis

15. Enrolment
7962 consecutive patients enrolled for elective or primary PCI in
144 hospitals across 23 countries

16. ENOXAPARIN ALL COMERS BCH
( N = 1111)
NON PAMI
( N = 1038)
PAMI
( N = 73)
NO GP IIb (578)
ANGIOSEAL
105
GP II b (312 )
ANGIOSEAL 45
NO GP II b 43
NO MAJOR
BLEED
GP II b (30)
1 DIED OF GI
BLEED
NO GP II b 43
NO MAJOR
BLEED

17. Independent predictors of
bleeding

18. Antiplatelet strategy in patients
on OAC
• Should we stop or continue OAC pre PCI?
• Should we bridge with heparin?
• Post PCI triple drug therapy or dual drug ?

19. Peri procedural management
P. Karjalainen, EUROPCR, 2013
Current guidelines recommend that in AF-patients with ine or
more stroke factors (CHA2DS2-VASc score), OAC is recommended.
During elective angiography and PCI?
1)Discontinue OAC 5-7 days prior + Bridging heparin
2)Discontinue OAC (5-7 D) + no additional/ Briding heparin
3)Uninterrupted OAC with therapeutic INR level (2.0-3.0) .No
additional heparins

20. Wide variability in Practice on oral
anticoagulation therapy pts undergoing
coronary stenting
M.Valgimigli, EUROPCR, 2013
Tx at discharge in the CRUSADE registry among 1,247 pts with AF

21. A. Rubboli, EUROPCR, 2013

23. WOEST: Primary Endpoint: Total number of TIMI
bleeding events

24. WOEST: Secondary Endpoint( Death, MI, TVR, Stroke, ST

25. Take home message
Bleeding is as important as preventing ischaemic
complications
• Revisit bivalirudin with new protocol
• Consider enoxaparin - has less bleeding
• Continue OAC prior to PCI or cor.Angio-inr
around 2
• OAC And the inopyridine safer than OAC And
DAPT