TAVI and Valve Replacement Thromboprophylaxis

Warren Prokopiw

Pharmacy Resident 2011-2012

Case – Mr MW

• 76 yo

• Admitted 14 May for worsening CHF

• PMH: Aortic Stenosis, CVD (CABG x4 1980, PCI x3 stent 2008) AFib, CHF, Sinus bradycardia with pacemaker, COPD, DM, restless leg syndrome

• Echo: - jet velocity 3.45 m/s, EF 45% – mean gradient 26.4 mmHg

– aortic valve area 0.98 cm2

Aortic Stenosis

• Abnormal narrowing of aortic valve

• Caused by calcification

– Bases to leaflets

– Similar process to atherosclerosis

• Lipid accumulation

• Inflammation

• Calcification

Pathophysiology

• Obstruction develops over decades

• Pressure causes LV hypertrophy

– Decreased ejection fraction

– Insufficient coronary blood flow

– Resulting ischemia - further dysfunction

– Increased sensitivity to injury - RR = 50%

• Larger infarct

• Increased mortality

Natural history

• Affects 25% or adults over 65

• Risk factors – age, sex, hypertension, smoking,

hypercholesterolemia and diabetes mellitus

• Prolonged latent period – Wide variability in progression

• Symptoms - angina, syncope, or heart failure – Average survival 2-3 years

– Sudden cardiac death

Diagnosis

• Systolic murmur

• Echocardiogram

– Valve anatomy

– LV response – size and function

• Doppler Echo

– Jet velocity

Staging

Indicator Mild Moderate Severe

Jet velocity (m per second)

Less than 3.0 3.0–4.0 Greater than 4.0

Mean gradient (mm Hg)*

Less than 25 25–40 Greater than 40

Valve area (cm2) Greater than 1.5 1.0–1.5 Less than 1.0

• a disease continuum • no single value that defines severity

Management

• Medical

– Anti-hypertensives

– Lipid lowering - no impact

– Prophylactic antibiotics for infective endocarditis no longer recommended

• Surgical

– Valve replacement required once symptomatic

Management

Mechanical Valve Replacement

• Ball and cage – noisy and inefficient

• Single tilting disk – severe compromise if thrombosis

• Bileaflet – quiet, stable, efficient

– Most common today

• Require warfarin

Bioprostheic Valves

• Tissue types

– porcine aortic or bovine pericardial

• Bovine better hemodynamic performance

• Stented or not

– Attempts for better efficiency - not observed

– stented more common

• No warfarin

Comparison

• Mechanical valve more durable – Tissue valves deteriorate by 10-15 years

• Higher in younger patients

• Mechanical valve higher bleeding risk

• Recommendations – Mechanical if have other mechanical valve or

< 65 yo and can take warfarin

– Tissue if warfarin is contraindicated or >65 without other risk factors for thrombolembolism

Aortic Balloon Valvotomy

• Palliative option for inoperable patients

• Percutaneous approach to decrease severity

– Fractures calcific deposits in leaflets

• early improvement

• Restenosis and deterioration in 6-12 months

Transcatheter Aortic Valve Insertion (TAVI)

TAVI

• percutaneously delivered aortic heart valve

• trileaflet bovine pericardial tissue

• tubular slotted stent

• SAPIEN

Valve Placement

Partner Study

• prospective, un-blinded, multicentre RCT

• Two distinct arms

– High risk operable n=699

– Inoperable n=358

• Inoperable

– 50% predicted probability of mortality or serious irreversible complication by 30 days by 1 cardiologist and 2 cardiothoracic surgeons

Trial Flow

High Risk outcomes

Inoperable Outcomes

Overall, the benefit from TAVR in inoperable patients with symptomatic severe AS greatly exceeds the risk

Two year Results

• N Engl J Med 2012;366:1696-704

Rate of death from any cause

Rate of death cardiac causes

Rate of rehospitalization

Rate of death or stroke

Stroke

• Disturbing complication

– Higher in TAVI group

• 1 year (11.2% vs. 5.5%, P = 0.06)

• 2 years (13.8 vs. 5.5%, P = 0.01)

• 66% occurring in first 30 days

• Causes

– Thromboembolism at valve site

– Artherothromobic emboli from plaques in aortic arch dislodged during catheter manipulation

Antithrombotic Therapy

Valve Replacement

POD 1-5 Bridging

• Bioprothetic valves – No studies – no recommendations

• Mechanical valves – Evidence summary at 30 d – bridge to warfarin

– Use prophylactic UFH or LMWH (therapeutic or prophylactic) until INR stable

Tromboembolism % Bleed %

Prophylactic UFH 0.9 3.3

Therapeutic LMWH 0.6 4.8

Therapeutic UFH 1.1 7.2

Bioprosthetic Valves

• High clot risk first 3 months

– Varies by location

• Aortic - ASA over warfarin if in NSR

– increased risk of bleed with warfarin over ASA, no difference in events

• Mitral – warfarin INR 2.0 - 3.0

– risk of stroke up to 40 events per 100 patient years

– Warfarin lowered risk, higher INRs increased bleed

Bioprosthetic Valves

• Thromboembolism risk beyond three months

– Mitral position – 0.2 to 2.6% per year

– Aortic position – 0.2% per year

• If in NSR – ASA indefinitely

Mechanical Valves

• Warfarin to no anti-coagulation – 0.21 (CI ,0.16-0.27) RR of thromboembolism

– 0.11 (95% CI,0.07-0.2) RR of valve thrombosis

• Aortic – INR 2.0-3.0

• Mitral – INR 2.5-3.5 – More thrombogenic due to different

hemocynamic and flow over the valve

• Dual valves – Treat as per mitral

Mechanical Valves

• New meta analysis for addition of ASA to warfarin

– reduction in mortality

• (RR, 0.58;95% CI, 0.4-0.86)

– thromboembolic outcome

• (RR, 0.42; 95% CI, 0.21-0.81)

– increase in risk of major hemorrhage

• (RR 1.44; 95% CI, 1.00-2.08)

• Add ASA 50-100 mg to warfarin for patients with no risk of bleeding

Trascahterter Aortic Valves

• Bioprosthetic valve

• Non-drug eluting stent

• Clopidogel plus ASA x 3 months

– No studies for anti-thrombotic

– Extension of practice in coronary stenting

Questions?

References 1. Holmes DR, Mack MJ, Kaul S, Agnihotri A, Alexander KP, Bailey SR, et al. 2012 ACCF/AATS/SCAI/STS

Expert Consensus Document on Transcatheter Aortic Valve Replacement. Journal of the American College of Cardiology [Internet]. 2012 Jan 30 [cited 2012 Mar 14];59(13):1200–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22300974

2. Bonow RO, Carabello B a, Chatterjee K, de Leon AC, Faxon DP, Freed MD, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology [Internet]. 2006 Aug 1 [cited 2012 Mar 10];48(3):e1–148. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16875962

3. Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. The New England journal of medicine [Internet]. 2012 May 3;366(18):1696–704. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22443478

4. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and Thrombolytic Therapy for Valvular Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest [Internet]. 2012 Feb [cited 2012 Mar 3];141(2 Suppl):e576S–600S. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22315272

5. Wilson W, Taubert K a, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation [Internet]. 2007 Oct 9 [cited 2012 Mar 10];116(15):1736–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17446442