Anticoagulation and Antiplatelets in Coronary Angioplasty

Patients with High Hemorrhagic Risk- Indications and evidence for a tailored

treatment

Alexandra Lansky, MD

Yale University School of Medicine

University College of London

• Antiplatelet drugs

• Cox-1 inhibitors

• P2Y12 inhibitors

• Glycoprotein Inhibitors

• Oral Anticoagulants

• Vit K Antagonists

• Factor Xa inhibitors

• Antithrombins

• Indirect thrombin Inhibitors (Heparin, LMWH)

• Direct Thrombin Inhibitors (Bivalirudin)

Anticoagulation and Antiplatelets in

Coronary Angioplasty

High Hemorrhagic Risk

Clinical Senarios to Discuss

The Patient requiring anticoagulation

The Patient who bleeds

The Patient who needs surgery

What Stent?

What Drug?

How Long?

Impact of BARC type 3-5 Bleeding

on 1 Year Mortality

Prognosis of Bleeding after Stent

Implantation

P<0.001

Ndrepepa G et al. Circulation 2012

High Hemorrhagic Risk

Clinical Senarios to Discuss

Procedural anticoagulation Consideration

Bivalirudin vs Heparin + GPI in ACS

STEMI

AHA/ACC 2012 GPG

In Patients with STEMI Bivalirudin is the preferred

IV anticoagulant agent

NSTEMI

AHA/ACC 2012 GPG

In Patients with NSTEMI Bivalirudin OR Heparin

* GPI with high risk features not adequately treated with

P2Y12 (Class I a); adequately pretreated (Class IIb)

B

EUROMAX BRIGHT HEAT PPCI

N Center 65 82 1

N patients 2,198 2,194 1,812

- Bivalirudin 1,089 735 905

- Heparin 460 729 907

- Heparin + GPI 649 730 --

- Heparin bolus 60 IU/kg 100 IU/kg 70 IU/kg

- Bival Infusion 4.5 hrs 4.0 hrs No

- GPI Bail out 7.9% vs 25% 4.4% vs 5.6% 13.5% vs 15.5%

- New P2Y12 59% 0 89%

- Radial 47% 79% 81%

Current Controversies

Bivalirudin vs Heparin in STEMI

Recent Studies (6,200 pts)

Sabatine M. The Lancet 2014

Metananalysis:Bivalirudin vs Heparin

MACE

Sabatine M. The Lancet 2014

Metananalysis:Bivalirudin vs Heparin

Ischemic Events

GPI mainly in Heparin Arm

Provisional GPI in both Arm

Planned GPI in both Arm

Metananalysis:Bivalirudin vs Heparin

Bleeding and GPI Utilization

Increasing Bleeding According to

GPI Utilization L

og

od

ds

ra

tio

Favors

Heparin

Favors

Bivalirudin P:0.02

Presented at TCT September 2014

ESC 2014 Guidelines

High Hemorrhagic Risk

Clinical Senarios to Discuss

The Patient requiring anticoagulation

Incidence of Bleeding in Relation to Antithrombotic Therapy

Sørensen R et al. Lancet 2009;374:1967-74

40,812 patients with MI between 2005-2008

Yearl

y i

ncid

en

ce (

%)

Single

Therapy

Dual

Therapy

Triple

Therapy

0.0

0.0

20

.04

0.0

60

.08

0.1

0

0.0 0.5 1.0 1.5

OAC

Clopidogrel+ASA

ACTIVE W: OAC vs ASA+ Clopidogrel

6706 Pts with Afib at risk of Stroke C

um

ula

tive H

aza

rd R

ate

s

Years

3.93 %/year

5.64 %/year RR = 1.45

P = 0.0002

Lancet 2006 Jun 10;367(9526):1903-12.

Stroke, Non-CNS Systemic Embolism, MI & Vascular Death

Is OAC needed? Stroke Risk in Afib: CHADS-VASc Score > 2

Predicting Bleeding after Stent Implantation

HAS-BLED Score > 2

Management of Antithrombotic Therapy in Afib Patients

with ACS or Undergoing PCI: ESC

ESC WG Thrombosis Consensus Document: Lip G et al. Eur Heart J 2010;31:1311-18

Hemorrhagic

Risk Clinical Setting Stent Type Recommendation

Low

or

Intermediate

Elective BMS 1 month: ASA, Clop, OAC

Lifelong: OAC alone

Elective DES

3 months: ASA, Clop, OAC

3-12 months: Clop, OAC

Lifelong: OAC alone

ACS BMS/DES

6 months: ASA, Clop, OAC

6-12 months: OAC, ASA or Clop

Lifelong: OAC alone

High

Elective BMS 2-4 weeks: ASA, Clop, OAC

Lifelong: OAC alone

ACS BMS

4 weeks: ASA, Clop, OAC

1-12 months: OAC, ASA or Clop

Lifelong: OAC alone

Consensus Document: Antithrombotic Therapy In Patients With Atrial Fibrillation Undergoing Coronary Stenting

A North-American Perspective

Faxon D et al. Thromb Haemost 2011; 106: 571–584

High risk ST and low bleeding risk

Low risk ST and low bleeding risk

Any risk ST and high bleeding risk

BMS - Triple Rx for at least 1 mo then OAC+ single

AP for 12 mo

DES - Triple Rx for at least 6 mo then OAC+ single

AP for 12 mo

After 12 mo OAC indefinitely

BMS - Triple Rx for at least 1 mo then OAC+ single

AP for 12 mo

DES - not recommended

BMS - Triple Rx for at least 6 mo then OAC+ single

AP for 12 mo

DES - Triple Rx for 12 mo

Atrial fibrillation and a coronary stent with moderate/high stroke risk (CHADS2>1)

High Hemorrhagic Risk

Clinical Scenarios to Discuss

The Patient who bleeds

A 67-year-old Woman Admitted with melanotic stool

Risk factors: hypertension, dyslipidemia, chronic atrial fibrillation, and smoking, prior TIA

No history of bleeding diathesis

HPI:

- 4 weeks ago was hospitalized for STEMI, was treated with primary PCI to Prox LAD using drug-eluting stent, LVEF 40%

- Meds at discharge: ASA 325 mg/d qd, coumadin 5.0 mg alter with 2.5 mg /day, Clopidogrel 75 mg/d qd, Carvedilol 12.5 mg bid, Lisinopril 40 mg qd, rosuvastatin 20 mg qd

CHADsVAS= 4

Physical Findings

• BP 96/68 mm Hg;

• HR 110/min, irregular;

• RR 18/min, Sat – 96%

• Cardiac exam: normal S1, S2,

no murmurs or rubs

• Clear lungs

• Abdomen: soft, mild

tenderness in epigastrium,

normal bowel sounds

• Labs: Hgb – 9.2 g/dL (12.8

g/dL 1 months ago), Hct –

26%

Management

• 0.9% Sodium Chloride IV

• Blood type was defined

• Omeprazole IV was

started: 80 mg bolus

followed by 8 mg/hr

infusion

• Gastroenterologist was

called, and urgent

endoscopy was

performed

Endoscopy: a bleeding duodenal ulcer with

adherent clot

• Endoscopic treatment: epinephrine injection plus thermocoagulation to the point of vessel obliteration

• Campylobacter pylori (+)

Rockall Scoring System for Predicting Re-bleeding and Mortality Based on Endoscopic and Clinical Variables

Score

Age

<60 0

60-79 1

>79 2

Shock

None 0

tachycardia 1

Hypotension 2

Comorbidity

None 0

CAD, CHF, other major comorbidity 1

Renal failure, liver failure, malignancy 2

Diagnosis

Mallory Weiss tear or no lesion observed 0

All other diagnosis 1

Malignant lesion 2

Stigmas of recent hemorrhage

None or spot in ulcer base 0

Blood in the GI tract, clot, visible vessel in ulcer base

2

Rockhall TA et al: Lancet 1996:347: 1138-1140

Rockall Scoring and Prognosis after Upper GIB

Score Re-bleeding % Mortality %

1 3% 0%

2 5% 0%

3 12% 2%

4 13% 4%

5 17% 8%

6 30% 15%

7 40% 20%

8 48% 39%

Rockhall TA et al: Lancet 1996:347: 1138-1140

Post Endoscopy

Omeprazole infusion 8 mg/hr for 72 hrs, followed

by Omeprazole 20 mg qd

ASA discontinued, coumadin held

Clopidogrel 75 mg qd continued

Clarithromycin 500 mg bid and amoxicillin 1 g bid

for 2 weeks

No signs of continuing GIB for 2 weeks

Repeated EGDS: healing duodenal ulcer

coumadin restarted 2.5 mg/day

F/U: uneventful at 1 year

High Hemorrhagic Risk

Clinical Scenarios to Discuss

The Patient who needs surgery

Bleeding Risk in Various Surgeries

Bleeding Risk Clinical Severity Type of Surgery

Low • Transfusions

rare

• Peripheral: plastic/general, biopsies

• Minor orthopedic, ENT general

• Endoscopy

• Eye: anterior chamber

• Dental

Intermediate

• Transfusions may be frequent

• More re-op, LOS

• Visceral

• Cardiovascular surgery

• Major orthopedic, ENT

• Urologic reconstructive

High • Bleeding into a

closed space

• Intracranial

• Spinal

• Eye: posterior chamber

Adapted from Abualsaud and Eisenberg, JACC: CV Intv 2010

Late Surgery Group

(Beyond 3 months)

Early Surgery Group

(3 months)

3/34 8.9%

2 Deaths 1 MI

1/159 0.6% 1 MI

SENS Registry

p<0.001

Patients treated with ZES Undergoing Surgery and Discontinuing DAPT within 1 Year

Kim JW et al, ACC 2009

Patients undergoing PCI:

Treatment interruption

Strategies for Upcoming Surgery

• If at all possible, delay surgery!

Ideally 6 weeks for BMS*

• Less only if necessary

Ideally 6 months to 1 yr for DES*

• Likely 3-6 months with 2nd gen DES

• If surgery is needed and bleeding risk

low, continue DAPT through surgery