WHAT SHOULD WE DROP FOR MONOTHERAPY DROP THE

WHAT SHOULD WE DROP FOR MONOTHERAPY? DROP THE P 2 Y 12 Robert W. Yeh, MD MSc MBA Director, Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology Associate Chief, Interventional Cardiology, Beth Israel Deaconess Medical Center Associate Professor of Medicine, Harvard Medical School #CRT 2020 @rwyeh

Funding and Disclosures Industry Funding and Disclosures Abbott Vascular: Scientific Advisory Board, CTO Proctoring, Consulting, Investigator-initiated research grant Astra Zeneca: Consulting, Investigator-initiated research grants Boston Scientific: Scientific Advisory Board, CTO Proctoring, Consulting, Investigator-initiated research grants Medtronic: Scientific Advisory Board, Consulting, Investigator-initiated research grants SAFE-PAD Study ) –Co-PI) is jointly sponsored by Bard, Boston Scientific, Cook, Phillips, and Medtronic. Non-Industry Funding National Heart, Lung and Blood Institute R 01 HL 136708 (EXTEND Study) K 23 HL 118138 (DAPT Score) K 24 HL 150321

Evidence Supporting Dropping P 2 Y 12 Inhibitor Two separate questions: n Vs. Maintaining P 2 Y 12 inhibitor in high bleeding risk patients (traditional DAPT duration studies) – Lots of evidence n Vs. Dropping ASA in high bleeding risk patients – Little evidence Two separate populations: n Those not on anticoagulation – most evidence n Those on anticoagulation – no evidence 3

Dropping P 2 Y 12 Inhibitor Among HBR Patients (not on anticoagulants) Costa et al. Lancet 2016. 4

DAPT Score ≥ 2 vs. < 2 Helps Identify Suitable/Unsuitable Pts for Extending DAPT Duration Low DAPT Score patients are most often HARMED by longer DAPT duration High DAPT Score patients are most often HELPED by longer DAPT duration (and harmed by shorter duration) 5

Complex Coronary Lesions Costa et al. JACC 2019. 6

DAPT Score Can Identify Patients With Complex Coronary Disease Who Have Worse Outcomes with Longer DAPT Duration Event Rates in Complex Anatomy Patients Stent Thrombosis of MI Yeh, Kereiakes, Steg et al. , Circulation 2017. . DAPT Score | #AHA 19 Moderate/Severe Bleeding

ASA vs. P 2 Y 12 Monotherapy Comparisons n ASA monotherapy vs. P 2 Y 12 monotherapy after PCI: – CAPRIE Trial (1996, Full dose ASA, ASCVD population – GLOBAL LEADERS at 12 months onward n Monotherapy along with oral anticoagulation after PCI: – None – AUGUSTUS, PIONEER, REDUAL PCI – compared dropping ASA vs. not dropping ASA. Did not evaluate early discontinuation of P 2 Y 12. 8

1 Year Landmark Analysis in GLOBAL LEADERS 1, 8 1, 6 1, 4 1, 2 1 0, 8 Ticagrelor 0, 6 Aspirin 0, 4 0, 2 0 Death or MI 9 MI Definite BARC 3 or ST 5 Bleeding All differences Non-significant

The argument to drop the P 2 Y 12 inhibitor n Aspirin resistance is less prevalent than clopidogrel resistance. – Nearly twice the rate of clopidogrel resistance among patients with stent thrombosis and controls versus aspirin resistance 1 n Cost and ease of use, comfort n No dyspnea issues, once per day medication n ? Pleiotrphic effects of ASA Pinto Slottow, Waksman. AJC 2019. 10

17, 000 secondary prevention pts 42, 000 person-years 3306 vascular events Reduction in serious Vascular events, stroke and MI with aspirin vs. placebo. Lancet 2009. 11

Aspirin Withdrawal Biondi-Zoccai et al. EHJ 2006. 12

Conclusions –Monotherapy with ASA alone is the gold standard n Shortening DAPT results in lower NACE compared to longer DAPT durations in high bleeding risk patients (high PRECISE DAPT, low DAPT Score) n In most studies, shorter DAPT has meant P 2 Y 12 inhibitor discontinuation. n Little evidence supports aspirin early compared to stopping P 2 Y 12 early. n Aspirin is cheap, well tolerated, once per day with a long track records in patients with ASCVD. 13

Thank you! E: ryeh@bidmc. harvard. edu @rwyeh