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 Reddy 1 , Stacey L Amorosi 2 , Shannon Armstrong 3 , Susan S Garfield 3 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 outweigh the upfront procedural costs of LAAC

Background • Prevalence of AF in the United Cumulative Per-Patient Cost of States was estimated to range Ischemic Stroke (US) 3 from 2.7-6.1 million in 2010 1 $45,000 $38,712 $40,000 $36,515 • As many as 12 million Americans $32,900 $35,000 may have AF by 2050 1 $30,000 • AF patients have roughly 5 times $25,000 $20,604 the risk of stroke as non-AF $20,000 patients 2 $15,000 $10,000 • $11 billion is spent annually on the $5,000 direct medical costs of stroke in $0 the United States 1 90 days 1 year 2 years 3 years AF-related stroke is expensive and cost burden will increase as prevalence of AF increases Go, Alan S. et al. "Heart Disease and Stroke Statistics — 2013 Update: A Report From the American Heart Association". Circulation. 2013; 127: e6-e245. 1. Holmes DR, Atrial Fibrillation and Stroke Management: Present and Future, Seminars in Neurology 2010;30:528 – 536. 2. 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

PROTECT-AF Overview • Randomized FDA-IDE Trial – Can the WATCHMAN device replace Non-Valvular AF Warfarin? CHADs ≥ 1 • Efficacy Endpoint: – Stroke Randomization (1:2) – CV death (& Unknown) – Systemic embolism • Safety Endpoint Warfarin Watchman Anticoagulation Regimen • Implant to 6 weeks • Non-inferiority & Superiority – Warfarin (INR 2-3) for 6 weeks – Aspirin (81 – 325 mg) – Bayesian Sequential Design • 6 weeks to 6 months – Analysis at 600 pt-yrs & every 150 pt-yrs Follow-Up – Clopidogrel (75 mg) thereafter  1500 pt-yr – Aspirin (81 – 325 mg) • After 6 months – Follow-up till 5 years – Aspirin (81 – 325 mg)

Net Clinical Benefit Analysis Annual NCB by Risk Factor • Net clinical benefit (NCB) was calculated as the weighted sum of annualized event rates Risk Factor PROTECT AF CAP Registry (difference of warfarin and device) All patients 1.73 4.97* Prior stroke /TIA 4.30 8.68* CHADS 2 score =1 0.70 2.22* CHADS 2 score ≥2 2.00 6.12* • DE=Death * significant • ICH=Intracranial Hemorrhage • TE=Thromboembolism NCB as a Function of Time in PROTECT AF and • MB=Major Bleeding CAP • 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

CBA vs. CEA • 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 Analysis Cost Effectiveness Analysis A method for systematically A method for comparing relative costs and Purpose calculating and comparing benefits outcomes of two or more treatment and costs of treatment strategies strategies Costs are assessed against Costs are assessed in terms of clinical Overview monetized benefits outcomes The clinical benefit is monetized Defined clinically such as life years gained, Clinical through willingness-to-pay, human QALYs gained or events avoided Outcomes capital, or costs avoided Net Cost or Net Benefit Incremental Cost Effectiveness Ratio Output (Total Incremental Value of Benefits) (Incremental Cost)/(Incremental – (Total Incremental Costs) Effectiveness) Difficult to monetize benefits The value of the effectiveness measure is Challenge subjective

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 years 1,2 • US DRGs 3 were used to assign acute treatment costs and long-term disability costs • were taken from the literature 4 • Value of 1 year of life was varied across a range of published sources 5-8 , ranging from $25,000 to $200,000 Source Value Assumption based on NICE value for 1 year of quality life 5 $25,000 Internationally accepted value for 1 year of quality life 6 $50,000 Low end of values used in FDA analyses 7 $76,000 Results of Meta-Analysis on 3 decades of studies on value of statistical life 8 $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.

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 • Clinical probabilities were taken from the PROTECT AF trial of the Watchman Device compared to warfarin at 1065 patient years 1,2 Event Probability Event LAAC Warfarin Cost Procedural Stroke 0.011 NA $9,302-$17,355 (LAAC-warfarin) Pericardial Effusion 0.048 NA $1,199.31 COSTS 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 warfarin) Ischemic stroke 0.013 0.016 $9,302-$17,355 (LAAC- Systemic embolism 0.003 0.000 $5,387.23 All-cause mortality (LAAC) 0.030 0.048 Value of Life 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 of life Cost Benefit of LAAC Compared to Warfarin at 5 Years by Value of 1 Year of Life $50,000 $40,406 $40,000 $30,000 $20,000 $12,521 $6,673 $10,000 $1,051 $- $(2,321) $(10,000) $10,000 $25,000 $50,000 $76,000 $200,000 Values for 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 Cumulative Net Costs and Benefits of LAAC versus warfarin at $76,000 Value of 1 Year of Life $80,000 Benefits are $70,000 33 times $60,000 greater than Benefits $50,000 costs are 11% $40,000 of costs $30,000 $20,000 $10,000 $0 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