DUAL ANTIPLATELET THERAPY: Who, What, When, How Long?

William H. Matthai, Jr., MD FACC Professor of Clinical Medicine Perelman School of Medicine at the University of Pennsylvania The Players:

• Aspirin • Clopidogrel • Prasugrel • Ticagrelor Aspirin

• What dose: 81 mg once daily • Chewable • With concurrent NSAID? • Give ASA before NSAID Clopidogrel

• What dose: 75 mg once daily • Load? • Might as well use 600 mg • Indications? • CAD • PAD • CVD Prasugrel • What dose: 10 mg once daily • 5 mg if >75 yo or <60 kg • Load? • Always – 60 mg once • Indications? • PCI in patients with ACS • STEMI • NOT in medically managed patients or before PCI in ACS Ticagrelor

• What dose? 90 mg twice daily • Load? • Always -180 mg once • Indications • ACS • STEMI/PCI/Medical mgt • IIA recommendation for pre-cath DAPT • Mortality benefit? • Dyspnea

Concern: Bleeding

• Addition of clopidogrel to ASA • 1%/yr increase risk of major bleed • Prasugrel • 0.6% increase in bleeding c/w clopidogrel • Contraindicated with h/o CVA or TIA

Ticagrelor vs clopidogrel – PLATO Trial .

Fatal intracranial bleeding Ticagrelor – 11 Non-CABG Clopidogrel – 1 related major P=0.02 bleeding Ticagrelor - 4.5% Clopidogrel - 3.8% P=0.03 Is there really no increased bleeding risk with ticagrelor?

Wallentin L et al. N Engl J Med 2009;361:1045-1057. Bleeding risk

• H Hypertension 1 A Abn liver or kidney function 1 for each S Stroke 1 B Bleeding history 1 L Labile INR 1 E Elderly age, > 65 1 D Drugs (eg NSAIDS) or Alcohol 1 for each TOTAL 9 HAS-BLED Score – used for risk of bleeding with oral anticoagulation, but can provide an estimate of those at high bleeding risk. A score of 3 or more suggests a high bleeding risk. Pisters R et al. Chest 138:1093 (2010) So which one?

• Stable vascular disease – clopidogrel • ACS • consider ticagrelor when initiating DAPT • always consider bleeding risk when choosing between clopidogrel and either ticagrelor or prasugrel (and when considering OAC therapy)

And then there are stents…

• Same basic principles • Prasugrel and ticagrelor may be beneficial in NSTE-MI and STEMI • Bleeding risk is higher with more potent P2Y12 inhibitors • The longer DAPT is continued, the higher the bleeding risk Bleeding

Ischemic events Overarching principles

• Minimum duration of DAPT • BMS • SIHD - 1 month • ACS – 12 months • DES • SIHD – 6 months • ACS – 12 months

Overarching principles

• Minimum duration of DAPT • BMS • SIHD - 1 month • ACS – 12 months • DES • SIHD – 6 months • ACS – 12 months • Johnny Depp – “These are more like guidelines and can change”

Overarching principles

• A longer duration of DAPT may be beneficial in patients with a higher risk of ischemic events • A shorter duration of DAPT may be beneficial in patients with a high risk of bleeding • So who might these patients be? Balancing risk

Increased ischemic risk Increased bleeding risk Patient related - Prior bleeding - Older - OAC therapy - ACS - Female gender - Extensive CAD - Older - Diabetes - Low body weight - CKD - CKD or liver disease - LVEF <40% - Diabetes Procedure related - Anemia - Small stent (<3mm) - Chronic NSAID or steroid therapy - Long stent - EtOH - Bifurcation stent - In stent restenosis Reduce bleeding risk!

• PPI • DAPT and no h/o GIB – no • DAPT and h/o GIB – yes • DAPT and OAC - definitely Putting it all together

• SIHD • BMS – 1 month ASA/clopidogrel • Consider longer therapy if high ischemic risk and low bleeding risk • DES – 6 months ASA/clopidogrel • Consider longer therapy if high ischemic risk and low bleeding risk • Consider shorter therapy (3 mos) for high bleeding risk

Putting it all together

• ACS • BMS – 12 months DAPT with ASA • Prasugrel or ticagrelor preferred if low bleeding risk • Consider longer therapy if high ischemic risk and low bleeding risk • Consider shorter therapy (1 mo) for high bleeding risk

Putting it all together

• ACS • DES – 12 months DAPT with ASA • Prasugrel or ticagrelor preferred if low bleeding risk • Consider longer therapy if high ischemic risk and low bleeding risk • Consider shorter therapy (3-6 mos) for high bleeding risk

DAPT Score Age > 75 -2 Age 65 to <75 -1 Age < 65 0 Current smoker 1 Diabetes 1 MI at presentation 1 Prior PCI or MI 1 Stent diameter < 3mm 1 Taxus stent 1 CHF or LVEF < 30% 2 SVG PCI 2

Score < 2 unfavorable risk/benefit ratio for longer term DAPT Putting it all together

• ACS • CABG – 12 months DAPT with ASA • Restart P2Y12 inhibitor after surgery • Regardless of whether patient has stent

In summary… • Know “target” duration of DAPT • Evaluate ischemic risk • Evaluate bleeding risk • Consider longer therapy if high ischemic risk and low bleeding risk • Consider shorter therapy for high bleeding risk • “Heart Team” approach – call for consultation