Dr. Dev PahlajaniDr. Dev PahlajaniMD,FACC,FSCAIMD,FACC,FSCAI

ANTICOAGULATION IN COMPLEX PCI

Chief of Interventional cardiology

Breach Candy Hospital and Consultant Cardiologist

Nanavati Heart Institute,Mumbai

Anticoagulation in complex PCI

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

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;24:1815-23 2003;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 NSTEMI NSTEMI 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

Inho

spita

l dea

th (%

)In

hosp

ital d

eath

(%)

In hospital major bleedingIn hospital major bleeding YesYes

NoNo

Blood Transfusion is Associated with an Increased 30-Day Mortality in NSTEMI

Rao et al. Rao et al. JAMAJAMA 2004;292:1555-62 2004;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-day 30-day death ratedeath rate

TransfusionTransfusion

No TransfusionNo Transfusion

Log-rank Log-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 3030DayDay

8.00%8.00%

3.08%3.08%

Cum

ulati

ve m

orta

lity

Cum

ulati

ve m

orta

lity

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;295:1579-803. Jozic J. AJC 2006;98:36M

Sweet spot for P2Y12 inhibition

M.Valgimigli, EUROPCR, 2013

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

Anticoagulation strategies in complex PCI

OAC WITH ?DAPT? TOAT? SAPT

PPCI BIVALURIDIN,LMWH

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 clinicalevents

Major bleeding* MACE**

30 d

ay e

vent

rate

s (%

)

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

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)

PPValueValue

ARC definite or ARC 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

Acute Acute (≤24 hrs)(≤24 hrs) 0.3%0.3% 1.3%1.3% 0.00090.0009

Subacute Subacute (>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

WHY IS THERE AN EXCESS OF EARLY STENT THROMBOSIS IN HORIZONS AMI ?

Clopidogrel

BIVALIRUDIN

ASPIRIN

PPCI 24hrs

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

HORIZONS: Impact of pre-randomized heparin on Acute Stent

Thrombosis

Enrolment7962 consecutive patients enrolled for elective or primary PCI in

144 hospitals across 23 countries

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 43NO MAJOR

BLEED

GP II b (30)1 DIED OF GI

BLEED

NO GP II b 43NO MAJOR

BLEED

Independent predictors of bleeding

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 ?

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

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

A. Rubboli, EUROPCR, 2013

WOEST: Primary Endpoint: Total number of TIMI bleeding events

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

Take home messageBleeding 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