Stroke and Bleeding Risk Scores LAA Closure

An Alternative to Chronic Oral Anticoagulation

Brian Whisenant, MD October 2015

Disclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company Ownership/Founder: Coherex Medical Consultant/Speakers Bureau Boston Scientific

Comparison of Stroke Prevention Treatments in Non-rheumatic Atrial Fibrillation

19 clinical trials; 17,833 patients

Warfarin prevents 28 ischemic strokes at the expense of 11 major or fatal bleeding episodes

Suggests the need to tailor anticoagulant therapy to higher risk patients.

Cooper NJ, Et al. Arch Intern Med. 2006;166:1269-1275. Bleeding

Risk Stroke

Risk

Warfarin Aspirin Relative Risk Reduction Absolute Risk

Reduction

Strokes 2.4/100 pt yrs 3.8/100 pt yrs 38% 1.4%

Primary Prevention 0.7%

Secondary Prevention 7.0%

Historical Warfarin vs Aspirin Observation

Patients with atrial fibrillation and a history of stroke Have an annual stroke risk in excess of 7% Benefit of warfarin markedly outweighs risk of

bleeding unless bleeding risk is extreme

Additional data needed to stratify stroke risk among patients with AF and no history of stroke to justify chronic oral anticoagulation.

AFI Age > 65 Stroke or TIA Diabetes HTN

SPAF Women > 75 Stroke or TIA Clinical CHF or FS < 25% SBP > 160

CHADS2 CHF HTN Age > 75 Diabetes Ischemic stroke or TIA = 2 SBP > 160

Origin of the CHADS2 Score

Gage et al. JAMA, June 13, 2001

Condition Points C Congestive heart failure 1 H Hypertension 1 A Age 75 years 1 D Diabetes mellitus 1 S2 Previous stroke or TIA 2

0%

5%

10%

15%

20%

0 1 2 3 4 5 6

1.9% 2.8%

4.0% 5.9%

8.5%

12.5%

18.2%

CHADS2 Score

Annual Risk of Stroke

Validated in 1733 Medicare beneficiaries with AF during index hospitalization Patients with rheumatic valve ICD-9 codes were excluded

Bleeding with NOACs and Warfarin

Re-Ly Rocket AF Aristotle Dabigitran warfarin Rivaroxiban warfarin Apixiban warfarin

Major Bleeding 3.11 3.36 3.6 3.4 2.13 3.09

Intracranial bld 0.30 0.74 0.5 0.7 0.33 0.8

What stroke risk warrants risk: 3% major bleed & 0.7 0.8% ICH (warfarin) 0.3 0.5% ICH (NOAC)

0%

5%

10%

15%

20%

0 1 2 3 4 5 6

1.9% 2.8%

4.0% 5.9%

8.5%

12.5%

18.2%

CHADS2 Score

Annual Risk of Stroke

Stroke Prevention In AF Guidelines

CHADS2 (Annual stroke risk)

ACC/AHA/HRS CHEST ESC

0 (1.9%) No therapy No therapy No therapy or Aspirin

1 (2.8%) Antithrombotic Tx* OAC CHA2DS2-VASc

>2 (>4%) OAC OAC OAC

JACC Vol. 61, No. 18, 2013:193544 European Heart Journal (2010) 31, 23692429 Chest. 2012;141(2 Suppl):e531S-75S.

*Antithrombotic Tx = either antiplatelet or OAC

AFI Age > 65 Stroke or TIA Diabetes HTN

SPAF Women > 75 Stroke or TIA Clinical CHF or FS < 25% SBP > 160

CHADS2 CHF HTN Age > 75 Diabetes Ischemic stroke or TIA = 2 SBP > 160

Origin of the CHA2DS2-VASc Score

CHA2DS2-VASc CHF HTN Age > 75 = 2 Diabetes Stroke or TIA = 2 - Vascular Disease Age 65-74 Sex (female gender)

0%

3%

6%

9%

12%

15%

18%

0 1 2 3 4 5 6 7 8 9

0.0% 1.3%

2.2% 3.2%

4.0%

6.7%

9.8% 9.6%

6.7%

15.2%

Risk

of S

trok

e

CHA2DS2VASc Score

Annual Risk of Stroke

European Society of Cardiology Guidelines2

CHA2DS2-VASc Stratifies Low CHADS2

1 Lip GY et al, Chest. 2010;137(2):263-72 2 Camm AJ et al, Eur Heart J. 2010;31:23692429

Condition/Risk Factor Points

C Congestive heart failure 1 H Hypertension 1 A Age 75 years 2 D Diabetes mellitus 1 S2 Previous stroke or TIA 2 V Vascular disease 1 A Age 65-74 years 1 Sc Sex (female gender) 1

0%

3%

6%

9%

12%

15%

18%

0 1 2 3 4 5 6 7 8 9

0.0% 1.3%

2.2% 3.2%

4.0%

6.7%

9.8% 9.6%

6.7%

15.2%

CHA2DS2VASc Score

Annual Risk of Stroke

European Society of Cardiology Guidelines2

CHA2DS2-VASc Stratifies CHADS2 = 0, 1

1 Lip GY et al, Chest. 2010;137(2):263-72 2 Camm AJ et al, Eur Heart J. 2010;31:23692429

0%

5%

10%

15%

20%

0 1 2 3 4 5 6

1.9% 2.8%

4.0%

5.9%

8.5%

12.5%

18.2%

CHADS2 Score

Annual Risk of Stroke

JACC Vol 64, No 21, 2014

Bleeding Risk Scores

HEMORR2HAGES; HAS-BLED; ATRIA

HAS-BLED Score

Major Bleeding/

Year 0 1.13 1 1.02 2 1.88 3 3.74 4 8.7

HAS-BLED SCORING Each checkmark = 1 point: Hypertension (SBP>160 mm Hg) Abnormal:

Kidney function: creat > 2.26 Liver function: Bili >2x ULN and LFTs > 3x LN

Stroke history Bleeding history or predisposition Labile INRs: TTR < 60% Elderly > 65 years Drugs:

ETOH abuse ASA or NSAID use

0

1

2

3

4

5

6

0 1 2 3 4 5 6

CHA 2

DS 2

-VAS

c

HAS-BLED

Bleeding Risk Scores Clinical Implications

For patients at high bleeding risk (HAS-BLED > 3), consider: Frequent INRs (especially upon

initiation of OAC) Fall prevention interventions Lower dose OAC Avoid aspirin Left Atrial Appendage Closure as an

alternative to OAC

Increased bleeding usually associated with increased stroke. No therapy is a poor option.

Warfarin Dicontinuation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6

AF Patients

Using Warfarin

CHADS2 Score

As Stroke Risk Increases, Warfarin Use Decreases

Piccini. Heart Rhythm (2012)

p < 0.001

OAC Discontinuation

Treatment Study Drug

Discontinuation Rate Major Bleeding

(rate/year)

Rivaroxaban1 24% 3.6%

Apixaban2 25% 2.1%

Dabigatran3 (150 mg) 21%

3.3%

Edoxaban4 (60 mg / 30 mg) 33 % / 34% 2.8% / 1.6%

Warfarin1-4 17 28% 3.1 3.6%

1 Connolly, S. NEJM 2009; 361:1139-1151 2 years follow-up (Corrected); 2 Patel, M. NEJM 2011; 365:883-891 1.9 years follow-up, ITT. 3 Granger, C NEJM 2011; 365:981-992 1.8 years follow-up. 4 Giugliano, R. NEJM 2013; 369(22): 2093-2104 2.8 years follow-up.

The LAA is the source of AF mediated stroke

Thrombus

91% of AF associated thrombus is found in the left atrial appendage

The four largest TEE studies comprising 1,181 patients showed that 98% of thrombi were found in the LAA

Stroke Prevention in Atrial Fibrillation III, The Annals of Thoracic Surgery, 1996, 61:7559

WATCHMAN LAA Closure Device FDA Approval 3/2015

The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who: Are at increased risk for stroke and systemic embolism based on CHADS2 or

CHA2DS2-VASc scores and are recommended for anticoagulation therapy Have an appropriate rationale to seek a non-pharmacologic alternative

to warfarin, taking into account the safety and effectiveness of the device compared to warfarin.

American Heart Jo May 2006

Lancet Aug 2009

Circulation Feb 2013

WatchmanTrial Publications

Circulation Feb 2011

JACC March 2012

NEJM June 2009

JAMA November 2014

Left Atrial Appendage Closure as an Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation A Patient-Level Meta-Analysis JACC Vol. 65, No 24, June 23, 2015

Ischemic Stroke Across Watchman Studies Similar to Contemporary Warfarin Trials

Source: FDA Oct 2014 Panel Sponsor Presentation.

Imputed Placebo Analysis

AF Conclusions

Highest risk of AF mediated stroke: 1. Prior stroke 2. Rheumatic valve disease (mitral stenosis) 3. Hypertrophic cardiomyopathy

CHA2DS2-VASc score approximates annual stroke risk (0-4) 0 No therapy 1 No therapy, aspirin, OAC 2 OAC

HAS-BLED > 3 = >8% annual major bleeding (age, HTN = 2) h/o bleeding, aspirin, kidney, liver, falls, stroke LAA Closure is an alternative to OAC - more ischemic stroke, less hemorrhagic stroke than OAC - bleeding history or risk - unwilling to take OAC

Structural Heart Disease Program 801-507-4795

intermountainheartinstitute.org brian.whisenant@imail.org

Thank You

Stroke and Bleeding Risk ScoresLAA ClosureAn Alternative to Chronic Oral AnticoagulationDisclosure Statement of Financial InterestSlide Number 3Slide Number 4Historical Warfarin vs Aspirin ObservationSlide Number 6Slide Number 7Slide Number 8Stroke Prevention In AF GuidelinesSlide Number 10CHA2DS2-VAScStratifies Low CHADS2CHA2DS2-VAScStratifies CHADS2 = 0, 1Slide Number 13Slide Number 14Slide Number 15Slide Number 16As Stroke Risk Increases, Warfarin Use DecreasesSlide Number 18Slide Number 19Slide Number 20Slide Number 21Slide Number 22Slide Number 23Slide Number 24AF ConclusionsSlide Number 26