Appendage Closure Versus Warfarin for Stroke Prevention in Atrial - - PowerPoint PPT Presentation

A Cost Benefit Analysis of Left Atrial Appendage Closure Versus Warfarin for Stroke Prevention in Atrial Fibrillation

Vivek Y Reddy1, Stacey L Amorosi2, Shannon Armstrong3, Susan S Garfield3

1 Mt. Sinai School of Medicine, New York, NY, USA; 2 Boston Scientific, Natick, MA, USA; 3 GfK Bridgehead, Wayland, MA, USA

Financial Disclosures

The authors wish to disclose the following sources of funding: 1. This research was funded by Boston Scientific 2. Stacey L Amorosi is a paid employee of Boston Scientific 3. All other authors are paid consultants to Boston Scientific

Objectives

• This analysis sought to compare the cost benefit of left

atrial appendage closure (LAAC) to warfarin for stroke prevention in atrial fibrillation (AF)

• Additionally, it sought to estimate the crossover point at

which the clinical benefits of LAAC relative to warfarin

• utweigh the upfront procedural costs of LAAC

Background

• Prevalence of AF in the United

States was estimated to range from 2.7-6.1 million in 20101

• As many as 12 million Americans

may have AF by 20501

• AF patients have roughly 5 times

the risk of stroke as non-AF patients2

• $11 billion is spent annually on the

direct medical costs of stroke in the United States1

1. Go, Alan S. et al. "Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association". Circulation. 2013; 127: e6-e245. 2. Holmes DR, Atrial Fibrillation and Stroke Management: Present and Future, Seminars in Neurology 2010;30:528–536. 3. Mercaldi et al. "Long-Term Costs of Ischemic Stroke and Major Bleeding Events among Medicare Patients with Nonvalvular Atrial Fibrillation". Cardiology Research and Practice. 2012; 2012: article id 645469

$20,604 $32,900 $36,515 $38,712 $0 $5,000 $10,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $45,000 90 days 1 year 2 years 3 years

Cumulative Per-Patient Cost of Ischemic Stroke (US)3

AF-related stroke is expensive and cost burden will increase as prevalence of AF increases

PROTECT-AF Overview

• Randomized FDA-IDE Trial

– Can the WATCHMAN device replace Warfarin?

• Efficacy Endpoint:

– Stroke – CV death (& Unknown) – Systemic embolism

• Safety Endpoint
• Non-inferiority & Superiority

– Bayesian Sequential Design – Analysis at 600 pt-yrs & every 150 pt-yrs thereafter  1500 pt-yr – Follow-up till 5 years

Follow-Up Non-Valvular AF CHADs ≥ 1 Randomization (1:2) Warfarin Watchman

Anticoagulation Regimen

• Implant to 6 weeks

– Warfarin (INR 2-3) for 6 weeks – Aspirin (81 – 325 mg)

• 6 weeks to 6 months

– Clopidogrel (75 mg) – Aspirin (81 – 325 mg)

• After 6 months

– Aspirin (81 – 325 mg)

Net Clinical Benefit Analysis

• DE=Death
• ICH=Intracranial Hemorrhage
• TE=Thromboembolism
• MB=Major Bleeding
• PEF= Pericardial Tamponade
• NCB favored WATCHMAN as early as 3 months

post implant in CAP registry

• In PROTECT AF the NCB shifted from warfarin to

WATCHMAN between 6-9 months post implant

• 1. Gangireddy SR, Halperin JL, Fuster V, Reddy VY, Percutaneous left atrial appendage closure for stroke prevention in patients with atrial fibrillation: an

assessment of net clinical benefit. Euro Heart J 2012. doi:10.1093/eurheartj/ehs292

Annual NCB by Risk Factor

Risk Factor PROTECT AF CAP Registry All patients 1.73 4.97* Prior stroke /TIA 4.30 8.68* CHADS2 score =1 0.70 2.22* CHADS2 score ≥2 2.00 6.12*

NCB as a Function of Time in PROTECT AF and CAP

*significant

• Net clinical benefit (NCB) was calculated as the

weighted sum of annualized event rates (difference of warfarin and device)

CBA vs. CEA

Cost Benefit Analysis Cost Effectiveness Analysis Purpose

A method for systematically calculating and comparing benefits and costs of treatment strategies A method for comparing relative costs and

• utcomes of two or more treatment

strategies

Overview

Costs are assessed against monetized benefits Costs are assessed in terms of clinical

• utcomes

Clinical Outcomes

The clinical benefit is monetized through willingness-to-pay, human capital, or costs avoided Defined clinically such as life years gained, QALYs gained or events avoided

Output

Net Cost or Net Benefit (Total Incremental Value of Benefits) – (Total Incremental Costs) Incremental Cost Effectiveness Ratio (Incremental Cost)/(Incremental Effectiveness)

Challenge

Difficult to monetize benefits The value of the effectiveness measure is subjective

• Cost benefit analysis (CBA) and cost effectiveness analysis (CEA) are both

established health economic methodologies, although it is more common to see CEA in the clinical literature

Cost Benefit of Watchman vs. Warfarin

• A cost benefit model was constructed to estimate the total costs and benefits of LAAC

versus warfarin from a US-payer perspective

• Clinical probabilities were taken from the PROTECT AF trial at 1065 patient years1,2
• US DRGs3 were used to assign acute treatment costs and long-term disability costs

were taken from the literature4

• Value of 1 year of life was varied across a range of published sources5-8, ranging from

$25,000 to $200,000

• 1. Holmes DR et al, Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fi brillation: a randomised non-inferiority trial, Lancet 2009; 374: 534–42.
• 2. Reddy VY et al, Safety of Percutaneous Left Atrial Appendage Closure: Results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) Clinical Trial and the

Continued Access Registry, Circulation. 2011;123:417-424. 3. Fiscal Year 2013 Final Rule Tables. Centers for Medicare & Medicaid 2013.www.cms.gov, accessed August 1, 2013.

• 4. Taylor TN, Davis PH, Torner JC, Holmes J, Meyer JW, Jacobson MF, Lifetime cost of stroke in the United States. Stroke 1996;27:1459-1466. 5. National Institute for Clinical Excellence. Measuring effectiveness and cost

effectiveness: the QALY. National Institute for Clinical Excellence April 2010. 6. Grosse SD, Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. Expert Rev Pharmacoecon Outcomes Res. 2008 Apr;8(2):165-78. 7. Department of Health and Human Services: Center for Food Safety and Applied Nutrition, Food Labeling; Gluten-free labeling of foods, final regulatory impact analysis. Food and Drug

• Administration. Docket No. FDA-2005-N-0404. 8. Viscusi, Kip; Joseph E. Aldy (2003). "The Value of a Statistical Life: A Critical Review of Market Estimates Throughout the World". J Risk Uncertainty. 27 (1): 5–76.

Source Value

Assumption based on NICE value for 1 year of quality life5 $25,000 Internationally accepted value for 1 year of quality life6 $50,000 Low end of values used in FDA analyses7 $76,000 Results of Meta-Analysis on 3 decades of studies on value of statistical life8 $200,000

Characterizing Costs and Benefits

• Costs were defined as the incremental cost of treatment and

complications, both procedural and anticoagulant-related complications

• Benefits were defined as the savings achieved through reduction in

ischemic stroke, systemic embolism and mortality Net Cost Benefit=(cStroke(warf)-cStroke(laac)+vLifeYearsGained)- (cTreatment(laac)+cComplications(laac) -cTreatment(warf)+cComplications(warf))

Clinical Probabilities and Costs

Event Event Probability LAAC Warfarin Cost

COSTS (LAAC-warfarin) Procedural Stroke 0.011 NA $9,302-$17,355 Pericardial Effusion 0.048 NA $1,199.31 Device Embolization 0.006 NA $1,584.45 Procedural Major Bleeding 0.018 NA $6,155.45 Hemorrhagic stroke 0.001 0.016 $4,924-$11,153 Major bleeding 0.014 0.041 $6,155.45 BENEFITS (LAAC- warfarin) Ischemic stroke 0.013 0.016 $9,302-$17,355 Systemic embolism 0.003 0.000 $5,387.23 All-cause mortality (LAAC) 0.030 0.048 Value of Life

• Clinical probabilities were taken from the PROTECT AF trial of the

Watchman Device compared to warfarin at 1065 patient years1,2

• 1. Holmes DR et al, Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fi brillation: a randomised non-inferiority trial, Lancet 2009; 374: 534–42
• 2. Reddy VY et al, Safety of Percutaneous Left Atrial Appendage Closure: Results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) Clinical Trial and the

Continued Access Registry, Circulation. 2011;123:417-424

Results

• At 5 years, cost benefit varied depending on the value assigned for 1 year
• f life

$(2,321) $1,051 $6,673 $12,521 $40,406

$(10,000) $- $10,000 $20,000 $30,000 $40,000 $50,000

$10,000 $25,000 $50,000 $76,000 $200,000

Values for 1 Year of Life

Cost Benefit of LAAC Compared to Warfarin at 5 Years by Value of 1 Year of Life

PROTECT AF

Results

• The costs of LAAC outweigh the benefits in the immediate years following the

procedure

• This is to be expected since the entirety of treatment costs for LAAC are accrued

in the first year while benefits accrue over time

$0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10 Cumulative Incremental Costs Cumluative Incremental Benefits at $76,000

Cumulative Net Costs and Benefits of LAAC versus warfarin at $76,000 Value of 1 Year of Life

Benefits are 11%

• f costs

Benefits are 33 times greater than costs

$(50,000) $- $50,000 $100,000 $150,000 $200,000 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10 $25,000 $50,000 $76,000 $200,000 Net Benefit of LAAC compared to Warfarin Over 10 Years with 4 Values for Year of Life

Results

Sensitivity Analysis

• One-way sensitivity analysis reveals mortality rates to be the biggest drivers
• f cost benefit
• LAAC procedure costs and the value of one year of life were also significant

drivers

• No other model parameters influenced outcomes enough to change 5-year

cost benefit results

Conclusions

• A positive cost benefit is achieved with LAAC relative to warfarin in the early years

following device implantation

• LAAC costs are incurred up front, and benefits accrue over time
• Conversely, with warfarin, costs accrue slowly, but benefits diminish over time as

patients age into higher risk of bleeding complications

• LAAC represents a net benefit within 3-6 years depending on how 1 year of life is

valued

• This analysis provides decision makers with a tool for considering the value of

reduced mortality when assessing comparative effectiveness of stroke prevention in AF

• LAAC represents substantial long-term value to the US healthcare system