Cost-effectiveness of LAA Closure CRT 2016 February 20-23, 2016 Washington, DC, USA Cost-effectiveness of LAA Closure Sameer Gafoor1,2 . 1CVC Frankfurt: Jennifer Franke, Simon Lam, Stefan Bertog, Laura Vaskelyte, Ilona Hofmann, Markus Reinartz, Horst Sievert 2Swedish Heart and Vascular: Ming Zhang, John Petersen II, Eric Lehr, Madalena Petrescu, Nimish Muni, Paul Huang, Darryl Wells, Adam Zivin, Eric Williams, Robert Bersin, Glenn Barnhart, Samuel Youssef, Pat Ryan, Irina Penev, Amanda Ray, Michelle Batjargal, Thearry Deap, Zachary Newhart, David Mazza, Heather Garcia CVC: CardioVascular Center Frankfurt, Frankfurt, Germany Swedish Heart and Vascular: Swedish Medical Center, Seattle, WA, USA

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A step back…

How much is this costing us? Review of 184 population studies 2010: 33.5 million cases, 5 million new/year US: 1.2 million cases in 2010 to 2.6 million by 2030 Why is prevalence increasing Other interventions and medications that increase lifespan 0.5-1%, more with age 2010: 596.2/100,000 men and 373.1/100,000 female

What about hospitalizations? 3,960,011 hospitalizations with afib as primary diagnosis from 2000-2010 Majority with Medicare/Medicaid as primary payer (70%) South: 38.5%, Midwest 24.9%, Northeast 22.2%, West 14.4% Co-morbidities of HTN, DM, COPD Length of stay is 3 days From 2000-2010, Decrease in going home (80% now 70%) and now more likely to facility (8.1% to 11.5%)

Trend by region increasing

Inpatient cost of AF 2001: $6410, 2010: $8439 2001: $6410, 2010: $8439 Highest with CHF and valve disorders More with age

LOS higher with CHADS2 score

Cost of Hospitalization up with CHADS2 score

What is a cost-effectiveness analysis? Relative costs from each course of action Gives you a ratio Numerator is cost associated with health gain Denominator is gain in health associated Common outcomes Quality-adjusted life years ICER = Incremental cost-effectiveness ratio Cost per QALY is important (<$50,000/QALY in US, €30,000/QALY in Europe)

What is a cost-utility analysis? Usually four quadrants with a cost-effectiveness plane (costs on y axis, QALY gained on x axis) I. less effective II: more effective & & more expensive more expensive III. Less effective IV. More effective & & less expensive less expensive

What about patients who are candidates for warfarin?

Model at 20 years lifespan, events possible every 3 months

Model at 20 years lifespan, events possible every 3 months

Clinical inputs from literature LAAC Warfarin NOAC Aspirin None RR ischemic stroke (rel warfarin) post-therapy 0.95 0.33 (rel to no therapy) 0.92 0.78 (rel no tx) 1 RR hemorrhagic stroke (rel warfarin) 0.15 1.00 (rel to HAS-BLED) 0.48 0.50 RR post-therapy major bleeding 0.55 NA 0.5 (rel warf) % major bleed hem. CVA 41.8% RR extracranial hem (rel warfarin) 1.25 0.30 Annual risk of systemic embolism 0.20% 0.40% 1.96 (rel warf) RR MI (rel warfarin) 1.47%/yr 0.97 2.00 Risk of minor bleeding Based on regimen 7.70% 8.70% 1.40%

(lower utility = worse off) With LAAC, less likely to have a disabling/fatal stroke (lower utility = worse off) (lower utility = worse off)

Add up the costs

Add up the costs

Cost over time

Time to effectiveness at 5, 10, 15, 20y

At 3 years, LAAC has more QALY than warfarin and at 5 years more QALY than NOAC For cost/QALY comparison, to reach <$50,000, it takes 7 years for LAAC vs. warfarin and 5 for LAAC vs. NOAC In a way – instead of numbers needed to treat (NNT), think of years to be more cost-effective (Time to cost-effectiveness)

At 20y, LAAC is more effective and less expensive than warfarin

At 20y, LAAC is more effective and less expensive than NOAC

At 20y, NOAC is more effective, but more expensive than warfarin k

What did we learn LAAC cost-effective to warfarin at 7 years; NOAC takes 16 years LAAC had fewer disabling strokes LAAC is more effective and less expensive Adherence is an issue in NOAC

What about patients contraindicated for warfarin?

Methods 3 studies CEA from German perspective 20 year time horizon ASAP – watchman device ACTIVEA – aspirin and clopidogrel AVERROES – apixaban CEA from German perspective 20 year time horizon

Flowchart (LAAC until death or 20 years)

% chance with LAAC, Aspirin, Apixaban Relative risk of ischemic stroke 0.23 (relative to no therapy) 0.78 (relative to no therapy) 0.37 (relative to aspirin) Annual risk of systemic embolism 0.12% 0.4% 0.1% RR of hemorrhage 1.1 0.65 1.16 % hemorrhage that is ICH 21.2% 17.8% 25% % hemorrhage that is GIB 52% 41.7% 27.3% Annual risk AMI 0.86% 0.9% 0.8%

Costs Event Cost (euro) G-DRG LAAC device, proc €9,136 F95A Minor isch. stroke €8,249 B39C Major isch stroke €31,829 B39A, B42A Minor hem stroke €4,357 B70D, B70E Major hem stroke €16,802 B70A, B, B44C TIA €3,999 B69ABCD Major GIB €2,096 G69A,67BC, G73Z Major other bleed €1,301 D62Z Cost of functional independence post-stroke/qtr €875 NA Cost of Moderate disability post-stroke/qtr €2,745 Cost of Severe disability post-stroke/qtr €4,285 Quarterly cost of aspirin €11 Quarterly cost of apixaban €292

Over 20 years… costs/year

What happens with the ICER at 10 years? Incremental Cost-effectiveness ratio Baseline risk (8.6% stroke risk) LAAC €15,837  4.82 QALY  dominates over aspirin (€21,077) or apixaban (€18,869) alone High risk patient (10.9% stroke risk) LAAC €19,236  4.53 QALY  dominates over aspirin (€29,021) or apixaban (€25,596) alone Low risk patient (2.2% stroke risk) LAAC €12,529  5.03 QALY  ICER €46K-€51K Not so great, but this is the CHADS2 <1 patient!

How does ICER look on a graph at 10 years?

Why does this work? LAAC has more QALY than aspirin at 2 years and apixaban at 4 years LAAC dominant (cost-saving and more effective) over both aspirin and apixaban by 7 years Adherence to aspirin and apixaban is a big deal  in AVERROES, 17.9% of apixaban group discontinued therapy Adherence is guaranteed with LAAC Limitations: 1 event/3 month cycle, from RCT, German costs only, only with studies that were listed, and only for Watchman

Future work Cost-effectiveness incorporated in the decision-making tool Use of this data in other countries and by US payors Expansion of this to younger patients with longer lifespans – more likely to be cost-effective