ANTITHROMBOTIC THERAPY IN CARDIAC VALVE SURGERY

Geoffrey Barnes, MD, MSc, FACC, FAHA, FSVMVascular and Cardiovascular MedicineUniversity of Michigan, Ann Arbor, MI@GBarnesMD

Disclosures

Consultant: Janssen, Pfizer/BMS, Acelis Connected HealthBoard of Directors: Anticoagulation ForumGrant Funding: NHLBI, AHRQ, Blue Cross Blue Shield of Michigan

Clinical Case• 76yo man presents to clinic to discuss aortic valve stenosis

management• Progressive dyspnea, lightheadedness, some leg edema

• PMH: COPD (no O2), HTN, DM2, arthritis• Meds: Inhalers, Lisinopril/HCTZ, metformin, Aleve, ASA

81mg• Echo: Severe aortic stenosis, normal EF• LHC: No obstructive CAD

• Key Questions:• What antithrombotic therapy will he need based on type of valve

replacement?• What strategies can be employed to reduce his bleeding risk?

Heart Valve Disease

• Marked reduction in the risk of rheumatic heart disease in the last century

• Valvular heart disease prevalence ~ 2.5% general population

• Increases to 10% in age > 75 years

J Am Coll Cardiol. 2016 Dec 20;68(24):2670-2689.

Types of Heart Valves Replacements

Mechanical heart valves• Strong, long lasting (20+ yrs)• Thrombogenic (anticoagulation)Bioprosthetic heart valves• Created from porcine aortic valves or bovine pericardium• Less thrombogenic (+/- anticoagulation)• Lasts ~10 to 20 years• Transcatheter Aortic Valve Replacement (TAVR)

Tip: Avoid term “prosthetic” heart valve – too ambiguous

Antithrombotic Therapy for Heart Valve Replacement

• All present risk for thrombosis and stroke

Characteristic Higher TE Risk Lower TE Risk Material Mechanical Bioprosthetic

Design Caged-ball, tilting disc

Bi-leaflet

Position Mitral or tricuspid Aortic

Side of the heart Right Left

Time frame First 3 months > 3 months

J Am Coll Cardiol. 2016 Dec 20;68(24):2670-2689.

Intracardiac Pressures and Thrombosis Risk

Low PressureEasy to “block up”

High PressureHard to “block up”

Tricuspid, Pulmonic, and Mitral Valves

Aortic Valve

Antithrombotic Therapy for Mechanical Valve Replacement

Type Position Risk Factors AntithromboticTherapy

Mechanical Mitral Any mitral valve with or w/o risk factors

INR 2.5-3.5

Mechanical Aortic AF, previous TE, LV dysfunction, hypercoagulable state

INR 2.5-3.5

Mechanical Aortic No additional risk factors INR 2-3

‘On-X®’ Mechanical

Aortic No additional risk factors INR 2-3 x 90 days, then INR 1.5-2.0

Bioprosthetic Aortic orMitral

Low risk of bleeding INR 2-3 x 3-6 months

Nishimura RA, et al Circulation. 2017 Jun 20;135(25):e1159-e1195. PMID:28298458

ASA 81mg recommended for ALL mechanical valve patients

Thrombosis Risk with Mechanical Valves

0

2

4

6

8

10

Mechanical Valve

Risk

per

100

-pat

ient

-yea

rs

No Treatment Aspirin Warfarin

Circulation. 1994;89(2):635Chest. 2012;141(2 Suppl):e576SJ Am Coll Cardiol. 1995;25(5):1111

On-X Valve: Lower INR Goal?• PROACT trial compared two warfarin INR goals in patients

receiving aortic On-X valve • 2-3 x 3 months then INR 1.5-2.0 • 2-3 indefinitely

• All patients received aspirin 81mg daily

J Thorac Cardiovasc Surg. 2014

Apr;147(4):1202-1210..

2-3 indefinitely1.5-2.0 after 3 months

On-X Valve: Lower INR Goal?

Outcome Control Group (INR 2-3)

Test Group (INR 2-3; 1.5-2.0) P-Value

N=190755.7 patient-years

N=185675.2 patient years

Mean INR 2.50 ± 0.63 1.89 ± 0.49 P<0.0001

Major Bleeding N (%/year)

25 (3.31) 10 (1.48) P=0.032

Ischemic StrokeN (%/year)

5 (0.66) 5 (0.74) P=0.859

All ThromboembolismN (%/year)

12 (1.59) 18 (2.67) P=0.164

Composite (MB, TE)N (%/year)

39 (5.16) 30 (4.44) P=0.539

J Thorac Cardiovasc Surg. 2014

Apr;147(4):1202-1210..

Eikelboom JW et al. N Engl J Med 2013;369:1206-1214.

Kaplan–Meier Analysis of Event-free Survival

Dabigatran vs. warfarin in patients with mechanical AVR or MVR

Stopped early d/t excessbleeding and TE in the dabigatran arm

Dabigatran for Mechanical Heart Valves: RE-ALIGN

Thrombosis Risk: Mechanical vs. Bioprosthetic Valves

0

2

4

6

8

10

Mechanical Valve Bioprosthetic

Risk

per

100

-pat

ient

-yea

rs

No Treatment Aspirin Warfarin

Circulation. 1994;89(2):635Chest. 2012;141(2 Suppl):e576SJ Am Coll Cardiol. 1995;25(5):1111

Antithrombotic Tx for Valve Replacement ACC/AHA Guidelines 2021

JACC 2021;77:e25-e197

ASA – only when other indication AND low bleed risk; low quality evidence

INR Intensity for Mechanical AVR

• MAQI2 – 6 centers in Michigan, 2009-2020• Mech AVR with 1+ “Risk Factor”

• AF, prior TE, LV EF<45%, Hypercoag state

• Outcome• Thromboembolism, any bleeding, all-cause death• ISTH major/CRNM bleeding, minor bleeding

• Results• 146 patient with mech AVR + RF on warfarin (24.7% high intensity)• TTR 60% (INR 2-3), 54% (INR 2.5-3.5)• ASA use: 78% (INR 2-3), 56% (INR 2.5-3.5)• Primary outcome: High INR HR 2.58 (1.28-5.18)• Major/CRNM bleeding: High INR HR 1.92 (0.79-4.65)• Minor bleeding: High INR HR 2.91 (1.34-6.33)

Hanigan S, Am J Cardiol (in press)

Return to Case

• 76yo man with symptomatic aortic stenosis, no AFib

• What antithrombotic therapy?• Mechanical AVR: Warfarin INR 2-3 (no RF), no ASA

• On-X Mechanical AVR: Warfarin 2-3 x90 days, then 1.5-2.0• Bioprosthetic SAVR: Warfarin INR 2-3 x3-6 months, ASA 81

indefinitely• TAVR: DAPT or Warfarin INR 2-3 x3-6 months, ASA 81 indefinitely

• How to reduce bleeding risk?• No ASA if mechanical valve• Stop NSAID for pain relief• PPI if 2+ antithrombotic meds

Case #2

• 69yo woman with history of atrial fibrillation who develops symptomatic mitral regurgitation, planning for surgery

• PMH: HTN, Obesity, CAD• Meds: apixaban, losartan, atorvastatin

• Does she have “valvular” AF?• What anticoagulant is safe for her stroke prevention in AF?

10/26/2021

AHA/ACC/HRS AF Guidelines:Valvular AF

Circulation. 2014 Dec 2;130(23):e199-267J Am Coll Cardiol. 2019 Jan 21. pii:

S0735-1097(19)30209-8

2014 2019Mitral Stenosis,

ORMechanical or

Bioprosthetic Valve,OR

Mitral Valve Repair

Moderate-severe mitral stenosis

OR Mechanical heart valve

ACC/AHA Recommendations in Valvular Heart Disease & AFib

JACC 2021;77:e25-e197

DOACs in “Valvular” AF

J Am Heart Assoc. 2017;6:e005835. DOI: 10.1161/JAHA.117.005835Major Bleeding

DOACs in “Valvular: AF

J Am Heart Assoc. 2017;6:e005835. DOI: 10.1161/JAHA.117.005835IC Hemorrhage

RIVER Trial

AF + Mitral Bioprosthetic

Valve(n=1,005)

Rivaroxaban 20mg daily

(n=500)

Warfarin INR 2.0-3.0(n=505)

Follow up for 12 months

R

Primary Outcome:- Death, MACE, Major Bleeding

Outcome Measure:Restricted Mean Survival Time (RMST)- Difference in “area under the curves” between two groups

NEJM 2020;383:2117-2126

RIVER Trial

NEJM 2020;383:2117-2126

Characteristics Rivaroxaban (n=500) Warfarin (n=505) All (n=1005)

Age (Mean±SD) 59.4±2.4 59.2±11.8 59.3±12.1

Female 311 (62.2%) 296 (58.6%) 607 (60.4%)

Diabetes 74 (14.8%) 64 (12.7%) 138 (13.7%)

Prior stroke 63 (12.6%) 66 (13.1%) 129 (12.8%)

CHF 202 (40.4%) 188 (37.8%) 390 (38.8%)

CKD 7 (1.4%) 11 (2.2%) 18 (1.7%)

Median BMI (IQR) 26.6 (23.4-29.9) 25.5 (22.8-29.3) 26.0 (23.2-29.7)

Mean CHA2DS2-VASc 2.7±1.5 2.5±1.3 2.6±1.4

Valve Implant <3 months prior 94 (18.8%) 95 (18.8%) 189 (18.8%)

Valve Implant 3mo-1yr prior 91 (18.2%) 78 (15.4%) 169 (16.8%)

RIVER Trial

NEJM 2020;383:2117-2126

RMST Difference: 7.4 days (-1.4 to 16.3)p<0.001 for non-inferiority

Return to Case #2

• 69yo woman with AF and mitral regurgitation planning surgery

• Does she have “valvular” AF?• No! She has native valve disease

• Can she remain on DOAC?• Yes! DOAC safe unless mechanical valve (and rheumatic mitral stenosis)

Summary

• Valve Replacement• Mechanical: Warfarin (INR 2-3 for most), few need ASA• Bioprosthetic: Warfarin ASA• TAVR: DAPT or Warfarin ASA

• “Valvular AF”• Rheumatic MS or Mechanical valve• Ok to use DOAC for native valve disease, bioprosthetic,

TAVR

@GBarnesMD