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Challenges in the Long Term Use of Dual or Triple Antiplatelet Therapy Kwan S Lee MD FSCAI FACC Associate Professor of Medicine Sarver Heart Center University of Arizona Relevant Disclosures None Objectives • Understand differences between P2Y12 oral inhibitors • Understand differences in DAPT duration after PCI based on stent type • Recognize influence on DAPT duration based on stable or acute presentation • Understand DAPT score • Understand risk / benefit ratio on deciding duration of therapy • Issues related to triple therapy • Aspirin hypersensitivity • Bioabsorbable vascular scaffold Effects of Anti-Platelets Post PCI • Decrease risk of stent thrombosis – STEMI – NSTEMI • Prevention of ischemic events remote from stented area – Acute coronary syndrome – Ischemic stroke – Death • Increased risk of bleeding Which Drugs? • Aspirin at 75 – 100 (81 mg), continued indefinitely • In addition to oral P2Y12 inhibitor – Clopidogrel (Plavix) 75 mg once daily – Prasugrel (Effient) 10 mg once daily or mg once daily (patients week offset General Guidelines • DAPT Therapy – aspirin dose of 81 mg (range 75 mg to 100 mg recommended) • Reasonable to use ticagrelor over clopidogrel in ACS PCI patients (IIa-BR) • Reasonable to use prasugrel over clopidogrel in ACS PCI patients (IIa-BR) – No high risk of bleeding – NO HISTORY OF STROKE OR TIA (III-BR) DRUG CLOPIDOGREL PRASUGREL TICAGRELOR Class Thienopyridine Thienopyridine CTPT Pro / Direct Drug Prodrug Prodrug Direct Inhibition Irreversible Irreversible Reversible Metabolic Pathway Hepatic CYP P450 Intestine/hepati c CYP P450 Hepatic CYP P34/5 Conversion to active metabolite 15% 85% 90-100% Time to steady state inhibition hours post 600 mg 1-2 hours post 60 mg hours post 180 mg Level of inhibition at steady state Wide response in variability Predictable Predictable Pharmacodynamic offset 5-7 days Up to days 5-7 days Off target effects None significant None significant Inhibition of adenosine reuptake (dyspnea, bradycardia) Activation Pathways Schomig A; N Eng J Med 2009 Aspirin Hypersensitivity • No regimen excluding aspirin post PCI has been formally tested • Aspirin desensitization is preferred, supervised by allergist in an ICU setting • Rapid desensitization protocols • ACC recommends single oral P2Y12 antiplatelet therapy – clopidogrel / prasugrel / ticagrelor (Class 1, LOE B and C) • Do not use dual oral P2Y12 therapy • ACCP recommends considering cilostazol in place of aspirin (*contraindicated in CHF) • Dipyridamole not recommended as has been shown to not be effective in ACS • Potential role of vorapaxar unknown How Long? – Determine if BMS, DES or BVS – Categorize Indication for PCI into Stable Ischemic Heart Disease or Acute Coronary Syndrome – Evaluate Bleeding Risk – Is indication for triple therapy present? Bioabsorbable Vascular Scaffold ABSORB III vs EES DEFINITE / PROBABLE STENT THROMBOSIS ABSORB EES P value Composite 1.5 % 0.7% 0.13 Early: 0-30 days 1.1 % 0.7% 0.46 Acute 24 h to 30 days 0.9 % 0.1% 0.04 Late 31 days to year 0.5 % 0% 0.10 Definite 1.4 % 0.7% 0.21 Probable 0.2% 0% 0.55 Stable Ischemic Heart Disease Post PCI • In addition to 75-100 mg (81 mg) of aspirin (1-BNR) • Bare Metal Stent – At least month of clopidogrel (1-A) – >1 month may be reasonable if low bleeding risk & no events on DAPT (2b-A) • Drug Eluting Stent – At least months of clopidogrel (1-BR) – > months may be reasonable if low bleeding risk & no events on DAPT (2b-A) – If bleeding or risk high, may discontinue after months (2b-C-LD) • Bioabsorbable Vascular Scaffold – At least 12 months of clopidogrel / prasugrel or ticagrelor Acute Coronary Syndrome Post PCI • In addition to 75-100 mg (81 mg) of aspirin (1-BNR) • With either BMS, DES or BVS • At least 12 months of clopidogrel, prasugrel or ticagrelor (1-BR) • >12 months may be reasonable if low bleeding risk & no events on DAPT (IIb-A) • With BMS or DES, if bleeding or high risk may discontinue after months (IIb-C-LD) Factor Favoring Longer Duration DAPT (Increased Ischemic or Stent Thrombosis Risk) • Ischemic Events – – – – – – Advanced Age ACS Presentation Multiple prior MI Extensive CAD Diabetes Mellitus CKD • Stent Thrombosis – – – – – – – – – ACS Presentation Diabetes Mellitus LVEF 20 mm in length ) Bifurcations stents In-stent restenosis Factors Favoring Shorter Duration DAPT (Increased Bleeding Risk) • • • • • • • • • Prior bleeding Oral anticoagulant therapy Females Advanced age Low body weight CKD Diabetes mellitus Anemia Chronic steroid or NSAID therapy Discussion at 12 months • If no bleeding or cost issues • Consider DAPT score to decide continuation of thienopyridine up to 30 months post PCI • Note DAPT study did not include ticagrelor • Ticagrelor beyond year studied in PEGASUS TIMI-54 suggesting preference for 60 mg PO bid dose The DAPT Trial – 12 vs 30 months post DES Moderate or Severe bleeding 2.5% vs 1.6% with thienopyridine Mauri L et al N Eng J Med 2014 The DAPT Score Low Risk Score = DAPT SCORE • Score or above prolonged DAPT favorable benefit / risk • Score 75 y -2 Age 65– 75 y -1 Age
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