Risk Scores to Guide DAPT Duration David J

Risk Scores to Guide DAPT Duration 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 CRT 2019 - 9 mins

Disclosures Grant Support/Drugs – Daiichi-Sankyo Grant Support/Devices – – Edwards Lifesciences Medtronic CSI V-Wave Medical - Abbott Vascular - Boston Scientific - Corvia Consulting/Advisory Boards – – Medtronic Janssen Pharmaceuticals - Edwards Lifesciences - Heartflow DJC: 2/19

History of DAPT after PCI/Stenting 1990 2000 1994 BMS approved No DAPT 2010 2003 SIRIUS, TAXUS 4 3 -6 months 1998 ISAR, STARS 1 month 2007 DES “Firestorm” 12+ months 2014 DAPT trial et al “Individualize”

DAPT Duration: How do we Decide? Palmerini T and Stone GW. EHJ 2016; 37: 353 -64

DAPT Bleeding and Ischemic Risk Scores • PARIS Scores (bleeding + ischemia) • DAPT Score (net benefit) • PRECISE DAPT Score (bleeding)

DAPT Bleeding and Ischemic Risk Scores • PARIS Scores (bleeding + ischemia) • DAPT Score (net benefit) • PRECISE DAPT Score (bleeding)

PARIS Ischemic Risk Score • Predicts composite of stent thrombosis or MI • Developed in 4, 190 pt all comer PCI registry, validated in the ADAPTDES registry – (C-stat=0. 65) Baber, Mehran, Guistino et al. JACC 2016.

PARIS: Gradient of Ischemic Risk By Score Low Risk (0 -2) Intermediate Risk (3 -4) High risk (≥ 5)

PARIS Bleeding Risk Score • Predicts BARC 3 or 5 bleed • Validated in ADAPT-DES (Cstat 0. 64)

Gradient of Bleeding Risk By Score Low Risk (0 -3) Intermediate Risk (4 -7) High risk (≥ 8)

PARIS Risk Scores: Summary • Can be used together to estimate ischemic and bleeding risks separately • Intuitive, plausible, easy to use, validated • Developed in all-comer population including patients on chronic anticoagulation highly generalizable • Key Limitation: PARIS bleeding and ischemic risk scores are correlated and share common variables – High risk bleeding patients are often also high ischemic risk

DAPT Bleeding and Ischemic Risk Scores • PARIS Scores (bleeding + ischemia) • DAPT Score (net benefit) • PRECISE DAPT Score (bleeding)

The DAPT Score Points Distribution of DAPT Scores among all randomized subjects in the DAPT Study 30% -2 -1 0 1 Current Smoker 1 Prior PCI or Prior MI CHF or LVEF < 30% Index Procedure Characteristic MI at Presentation Vein Graft PCI Stent Diameter < 3 mm 1 2 Percentage of Patients Variable Patient Characteristic Age ≥ 75 65 - 74 < 65 Diabetes Mellitus 25% 20% 15% 10% 5% 0% 1 2 1 -2 -1 0 1 2 3 4 5 6 7 8 9 10 DAPT Score 17

Continued Thienopyridine vs. Placebo Treatment Effect by DAPT Score Quartile (N = 11, 648) Q 1 = DAPT Score -2 to 0 Q 3 = DAPT Score 2 Q 2 = DAPT Score 1 Q 4 = DAPT Score > 2 Risk Difference (Continued Thienopyridine – Placebo), 12 -30 M 4. 0% 3. 0% Stent Thrombosis Q 1 Q 2 Q 3 Q 4 Myocardial Infarction Q 1 Q 2 Q 3 Q 4 GUSTO Moderate/ Severe Bleeding Q 1 Q 2 Q 3 Q 4 1. 97% 2. 0% 1. 17% 1. 0% 0. 69% 0. 03% -0. 07% -0. 06% -0. 73%-0. 59% -1. 0% -2. 0% -1. 34% -2. 18% -3. 0% -4. 0% -2. 56% -3. 48% 18

Risk Difference (Continued Thienopyridine – Placebo), 12 -30 M Continued Thienopyridine vs. Placebo Treatment Effect by DAPT Score Quartile (N = 11, 648) Mortality 4. 0% Net Adverse Events 3. 0% Q 1 Q 2 Q 3 Q 4 2. 0% 1. 0% Q 1 Q 2 Q 3 Q 4 1. 53% 0. 99% 0. 49% 0. 0% 0. 37% 0. 09% -0. 06% -1. 0% -2. 0% -1. 99% -3. 0% -4. 0% -3. 43% DAPT Score <2 DAPT Score ≥ 2 DAPT Score <2 19 DAPT Score ≥ 2 19 19

DAPT Score: Summary • Intuitive, plausible, validated, easy to use • Only score to simultaneously stratify bleeding and ischemic risk to identify high ischemic risk/low bleed risk patients (long DAPT) and low ischemic risk/high bleed risk patients (short DAPT) • Key Limitations: – Excludes certain patient types for whom risk prediction may be desirable (e. g. , pts on OAC or with prior h/o bleeding) – Only predicts benefit of extending DAPT from 12 to 30 months does not provide insight about shortening DAPT

DAPT Bleeding and Ischemic Risk Scores • PARIS Scores (bleeding + ischemia) • DAPT Score (net benefit) • PRECISE DAPT Score (bleeding)

PRECISE-DAPT Risk Score • Risk score to predict 1 -year major bleeding on DAPT • Developed using pooled data from 8 multicenter RCTs of varying DAPT duration • Bleeding endpoint = TIMI major or minor bleeding between 7 days and 1 year after PCI • Score based on patient characteristics available at time of index PCI procedure Costa F, et al. Lancet 2017; 389: 1025 -34

PRECISE Risk Score • Score (range 0 -100) includes 5 independent risk factors – – – Hemoglobin Age Prior bleeding -- WBC -- Cr. Cl • Top quartile (score >25) correlates with high risk of bleeding (2 -4%/year) • Available as web-based calculator (http: //www. precisedaptscore. com/predapt/ webcalculator. html) and phone app Costa F, et al. Lancet 2017; 389: 1025 -34

PRECISE Risk Score: Net Clinical Benefit • Net benefit of long DAPT positive in first 3 quartiles and only harmful in top quartile Risk Net Clinical Quartile Benefit 1 + 1. 4% 2 + 0. 8% 3 + 2. 0% 4 - 1. 2% Costa F, et al. Lancet 2017; 389: 1025 -34

Conclusions • The PARIS, PRECISE DAPT, and DAPT Scores are each useful to help make decisions regarding optimal dual antiplatelet therapy duration among PCI patients • The score one uses will depend on the patient profile and timing of decision, as well as the needs and specific tastes of individual clinicians • Using these tools in combination with clinical judgment is the most evidence-based method for determining optimal DAPT duration, and can support patient shared-decision making