What is the Optimal Rate of DES Use? David J. Cohen, M.D., M.Sc. Director, Cardiovascular Research Saint Luke’s Mid America Heart Institute Professor of Medicine University of Missouri- Kansas City TCT 2010 15 mins

Disclosures Grant Support/Drugs Grant Support/Devices Eli Lilly/Daiichi-Sankyo - Merck/Schering Plough Eisai Pharmaceuticals Grant Support/Devices MedRAD - Boston Scientific Edwards Lifesciences - Abbott Vascular Medtronic Consulting/Advisory Boards Medtronic - Eli Lilly/Daiichi-Sankyo Cordis - Boehringer-Ingelheim DJC: 9/10

International Variation in DES Use Pooled analysis of trends in DES use in 4 countries (178,000 lesions) Demonstrates marked variation in DES use both between countries and within countries over time Reasons for variation: Reimbursement Economic impact of repeat procedures Cultural/Sociological considerations Austin D, et al. Am Heart J 2009;158:576-84

Optimizing DES Use Expert opinion/consensus statements Cost-effectiveness modeling using predicted DES and BMS restenosis rates Natural experiment– look for differences in outcome by region or time period

Proposed Guidelines for DES Use Washington State Any one of the following Stent diameter ≤ 3.0 mm Stent length ≥ 15 mm Treatment of in-stent restenosis Diabetes Unprotected LM stenosis Any one of the following Vessel diameter <3.0 mm Lesion length >15 mm NICE (UK) Diabetes plus Lesion length >20 mm OR Vessel diam ≤2.75 mm Ontario

Implications of Guidelines for DES Utilization: Ontario Tech Assessment Characteristic Proportion of Lesions Diabetes 35.2% (A) Vessel diameter <=2.75 mm 39.1% (B) Lesion length >20 mm 18.9% Diabetes + (A or B) 18.7% n = 3310 lesions Lesion-Based Analysis

Implications of Guidelines for DES Utilization: NICE Guidance Characteristic Proportion of Lesions Vessel diameter <3.0 mm 42.1% Lesion length >15 mm 36.4% Either of the above 61.8% Lesion-Based Analysis

Implications of Guidelines for DES Utilization: Washington State Characteristic Proportion of Lesions Stent diameter <3.0 mm 74.0% Stent length >15 mm 70.2% Treatment of ISR 6.6% Diabetes 34.6% Treatment of unprotected LM 0.8% Any characteristic 93.4% n=13,945 lesions Lesion-Based Analysis

Optimizing DES Use Expert opinion/consensus statements Cost-effectiveness modeling using predicted DES and BMS restenosis rates Natural experiment– look for differences in outcome by region or time period

Cost-Effectiveness of DES (2010 data): Impact of Bare Metal Stent Restenosis Rate Healthcare system perspective Model Assumptions Incremental cost per DES = $1000 DES per case = 1.6 (case-mix adjusted) 50% reduction in TVR with DES vs. BMS (Kirtane metaanalysis) Conclusions: DES reasonably cost-effective when bare stent TVR rate > 11%

Distribution of Predicted TVR Rates with BMS Proportion with p(TVR) > threshold EVENT Waves 1-3 7447 patients/10,425 lesions Predicted TVR rate with DES and BMS based on logistic regression Age Previous PCI Reference diameter Lesion length SVG lesion LM lesion Implication Based on cost-effectiveness criteria, ~60% of U.S. PCI patients should receive DES 57% Stolker JM et al. Circ Cardiovasc Interv 2010;3:327-34 55% RRR

Optimizing DES Use Expert opinion/consensus statements Cost-effectiveness modeling using predicted DES and BMS restenosis rates Natural experiment– look for differences in outcome by region or time period

Temporal trends in DES use DES Firestorm “Liberal” use (N=7587) “Selective” use (N=2557) N=2535 N=2515 N=2535 N=2557

Study Concept Take advantage of this “natural experiment” in practice patterns to compare clinical outcomes and treatment costs between the “liberal” and “selective” DES eras Primary endpoint: TLR (most specific for DES effect) Secondary endpoints: death, MI, TVR, any revasc Economic endpoints: cost per patient, cost-effectiveness Should approximate the results of an RCT as long as there are no major differences in the overall PCI population or other aspects of care over the same time period

Clinical Outcomes: Death or MI Liberal vs. Selective DES Use Clinical Outcomes: Death or MI Death Death or MI Liberal DES use Selective DES use Liberal DES use Selective DES use Plogrank = 0.99 Plogrank = 0.30 4.6% 2.9% 4.6% 2.5%

Clinical Outcomes: Repeat Revasc. Liberal vs. Selective DES Use Clinical Outcomes: Repeat Revasc. TLR 5.1% 4.1% Plogrank = 0.03 TVR 6.5% 5.6% Plogrank = 0.07 Any Revasc 10.6% 10.1% Liberal DES use Selective DES use

Mean Cost per Patient Crude Cost-Effectiveness D = $454 (p<0.001) Liberal vs. Selective DES Use Mean Cost per Patient D = $454 (p<0.001) $15,104 $14,651 Repeat Revasc Antiplatelet Therapy Crude Cost-Effectiveness D Cost = $454 D TLR = 0.019 ICER = $24,000 per TLR event avoided Stents Initial Procedure (except stents) Liberal DES Use Selective DES Use

C-E Acceptability Curve: $/QALY Gained Liberal vs. Selective DES Use C-E Acceptability Curve: $/QALY Gained Risk-Adjusted Analysis ICER = $432,000/QALY gained Prob < $100,000 = 15% Willingness to Pay Threshold

Conclusions Currently, there is no clear consensus on the “optimal” rate of DES use If health care resources are unlimited, universal DES use is appropriate since virtually all patients and lesions benefit to some degree If health care resources are limited, both theoretical modeling and empirical data suggest that a more selective approach is reasonable-- aiming for 60-70% DES use across the PCI population (at current DES prices) Future research should be directed at developing methods to ensure that the “right” 60-70% of patients are treated