Optimal Duration of Dual Anti- Platelet Therapy. December 19, 2015

Transcription

1 Optimal Duration of Dual Anti- Platelet Therapy December 19, 2015 John S. MacGregor, M.D., Ph.D. Professor of Medicine University of California San Francisco Source: The New Yorker 1

2 Optimal Duration of Dual Anti- Platelet Therapy P2Y12 Inhibitors Optimal Duration of Therapy Interruption of Therapy Strategies with DAPT plus OAC 2

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5 Clinical Predictors of Stent Thrombosis Numerous factors integrate to predict development of stent thrombosis Patient factors Compliance with DAPT Genetic predisposition Diabetes, smoking, CKD Lesion factors Lesion length, complexity of lesion (including bifurcation) Stent factors Under expansion Alloy, Polymer, Drug 5

6 Overall Definite or Probable Stent Thrombosis Rates after STEMI 8.3% cumulative hazard at 5 years Mortality after Stent Thrombosis 6

7 STARS Trial 30 Day Stent Thrombosis Aspirin plus Ticlopidine 0.5% Aspirin Alone 3.6 Aspirin plus Warfarin 2.7 Leon, NEJM (1998), 339:

8 P2Y12 Antagonists Agent Route Prodrug? Reversible? Onset of ac7on Offset of ac7on Status Ticlopidine Oral (BID) Yes No 6 hours ~5 days Approved 1991 Clopidogrel Oral (QD) Yes No 2 to 8 hours Prasugrel Oral (QD) Yes No 0.5 to 4 hours Ticagrelor Oral (BID) No Yes 0.5 to 2 hours ~5 days Approved 1997 ~5 days Approved 2009 ~1 to 3 days Approved 2011 Cangrelor IV No Yes Immediate 60 minutes Approved 2015 Clopidogrel v. Newer P2Y12 Antagonists Study Year Follow- Up Comparison Stent Throm- bosis TRITON months Clopidogrel Prasugrel PLATO months Clopidogrel Ticagrelor CHAMPION hours Clopidogrel Cangrelor CHAMPION PHOENIX hours Clopidogrel Cangrelor OASIS days Clopidogrel 2X Clopidogrel 2.4% P Value < < TIMI Major Bleeding P Value Adapted from Claessen, (2014) JACCI, 7:

9 Transi_on Strategies from Cangrelor to Oral An_platelet Therapy April 2015 P2Y12 Inhibitors: Cau_ons/Warnings and Considera_ons Clopidogrel - Consider alterna_ve in CYP2C19 poor metabolizer - Avoid use with drugs that are moderate to strong CYP2C19 inhibitors Prasugrel - Not recommended for age >75, weight <60 Kg or prior stroke/tia - Significantly increased fatal bleeding (0.4% v. 0.1%; p=0.002) Ticagrelor - Maintenance dose of aspirin >100mg/day reduces effec_veness - Incidence of Dyspnea (blocks reuptake of adenosine by RBCs) - BID dosing 9

10 DAPT Trial 9961 pa_ents with DES randomized aier 12 months of DAPT to either con_nue DAPT for 18 months or d/c thienopyridine and take ASA alone Co- primary end points were ST and MACE Primary safety end point, moderate or severe bleeding Mauri, NEJM, 371:2155 MACE: L- DAPT vs S- DAPT Mauri L, et al. 10

11 MACE: L- DAPT vs S- DAPT Incidence of All Cause Mortality L- DAPT vs S- DAPT Mauri L et al. Eur Heart J November

12 All Cause Mortality S- DAPT vs L- DAPT Yeh R, et al. Lancet 386 October 17, 2015 Cumulative Incidence of Dual Antiplatelet Cessation (PARIS Study) Mehran R et al. Lancet

13 Risk of MACE (PARIS Study) Mehran R et al. Lancet 2013 One year Clinical Outcomes According to 6 Month DAPT Adherence Any Nonadherence (n = 208) Full Adherence (n = 1,951) P Value All- cause mortality Cardiac death MI Death or MI <0.001 Definite or Prob. ST Major bleeding <0.001 Stroke <0.001 Cutlip, (2015) JACCI; 8:

14 ITALIC Trial 2,031 pa_ents not resistant to ASA were randomized to either 24 months or 6 months of DAPT. Xience V stent Primary end point: Death, MI, emergency TVR, stroke, or major bleeding ITALIC Trial MACE: S- DAPT vs L- DAPT 14

15 MI: S- DAPT vs L- DAPT Major Bleeding: S- DAPT vs L- DAPT 15

16 Outcomes: L- DAPT vs S- DAPT Death Major Bleeding Collet J, et al. Lancet 384, 2014 Considerations for Temporary Discontinuation of DAPT Duration of therapy? Complexity of anatomy (multiple stents, overlapping, bifurcation, LM/prox LAD)? Caliber of vessels stented? Type of stent? Minimize time off DAPT (5 d), resume as soon as possible with loading dose Do not stop ASA if possible 16

17 ACC/AHA Recommendations Consider doing surgery on DAPT Continue aspirin, if possible Resume DAPT as soon as possible after surgery (loading dose) Do surgery in a facility with available cath lab with PCI capability Monitor patient Grines, Circ (2007)115: ACC/AHA Guidelines: An_platelet Therapy for NSTE- ACS (2014) CLASS I Pa_ents on chronic ASA should take 81 to 325 mg of non- enteric coated ASA prior to PCI. Pa_ents not on ASA should take 325 mg ASAP prior to PCI. Aier PCI ASA should be taken indefinitely at a dose of 81 to 325 mg per day. 17

18 ACC/AHA Guidelines: An_platelet Therapy for NSTE- ACS (2014) CLASS I A loading dose of P2Y12 inhibitor should be given prior stent procedure. Clopidogrel 600 mg Prasugrel 60 mg Ticagrelor 180 For pa_ents with NSTE- ACS and high- risk features, who are not adequately pre- treated with clopidogrel or _cagrelor, GP IIb/IIIa inhibitor is useful. ACC/AHA Guidelines: An_platelet Therapy for NSTE- ACS (2014) CLASS I In pa_ents receiving a stent (BMS or DES) for NSTE- ACS, P2Y12 inhibitor therapy should be con_nued for at least 12 months. - Clopidogrel 75 mg/day - Prasugrel 10 mg/day - Ticagrelor 90 mg BID 18

19 ACC/AHA Guidelines: An_platelet Therapy for NSTE- ACS (2014) CLASS IIa It is reasonable to choose _cagrelor over clopidogrel. It is reasonable to choose prasugrel over clopidogrel in pa_ents not at high bleeding risk. ACC/AHA Guidelines: An_platelet Therapy for NSTE- ACS (2014) CLASS IIa If the risk of morbidity from bleeding outweighs the an_cipated benefit, early discon_nua_on of P2Y12 inhibitor (eg, <12 months) is reasonable. CLASS IIb Con_nua_on of DAPT beyond 12 months may be considered. 19

20 Strategies for DAPT Decision Making DAPT and OCT: WOEST Study Any Bleeding MACE Dewilde W, et al. Lancet 2013; 381:

21 MACE and Major Bleeding: ISAR- TRIPLE Trial ACC/AHA Guideline: Triple Therapy (Circ. 2014) Class I The dura_on of triple an_thrombo_c therapy with a vitamin K antagonist, aspirin, and P2Y12 receptor inhibitor should be minimized to the extent possible to limit the risk of bleeding. Proton pump inhibitor should be prescribed in pa_ents with a history of GI bleeding. 21

22 ACC/AHA Guideline: Triple Therapy (Circ. 2014) Class IIa Proton pump inhibitor use is reasonable in pa_ents without a history of GI bleeding. Class IIb Target INR to lower end of therapeu_c range (2.0 to 2.5). 22