Strategia antitrombotiche nel paziente con fibrillazione atriale sottoposto a PCI Andrea Rubboli U.O. Cardiologia - Laboratorio di Emodinamica Ospedale Maggiore, Bologna Nucleus Working Group Thrombosis - ESC Direttivo Gruppo ATBV

DISCLOSURE INFORMATION Andrea Rubboli Dichiaro che negli ultimi due anni ho avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario: Astra Zeneca Bayer Boehringer Ingelheim Daiichi Sankyo Pfizer BMS

Recurrent ischemic events Need to prevent … Stroke Bleeding Recurrent ischemic events + stent thrombosis

Recurrent ischemic events PCI Stroke Recurrent ischemic events + stent thrombosis OAC DAPT (ASA + P2Y12 inhibitor) Stronger Weaker AF

Triple therapy of OAC, aspirin, and clopidogrel (Class IIa; LOE C) Recommendation: Triple therapy of OAC, aspirin, and clopidogrel (Class IIa; LOE C) Lip GY et al. Eur Heart J 2014;35:3155-79

Triple therapy (warfarin) vs. DAPT MACE = CV death + MI + thromboembolism Singh PP et al. Ther Adv Cardiovasc Dis 2011;5:23-31

Bleeding avoiding strategies limit peri-procedural bleeding* 2. reduce intensity of (warfarin) OAC** 3. avoid newer P2Y12 inhibitors (i.e., prasugrel, ticagrelor) in triple therapy 4. limit duration of triple therapy 5. reduce intensity of antithrombotic therapy#(?) # by withdrawing aspirin

Dual vs. triple therapy: the WOEST study 1° endpoint - Safety (total bleeding) 2° endpoint - Efficacy (stroke, death, MI, re-PCI/CABG, stent thrombosis) Dewilde WJ et al. Lancet 2013;381:1107-15

Sicurezza Efficacia Lo studio WOEST Trascinata da mortalità NON cardiaca Sottodimensionato per trombosi di stent Sicurezza Efficacia Trascinata da emorragie NON maggiori Rubboli A, Limbruno U. G Ital Cardiol 2013;14:564-8

Recommendations: Triple therapy of OAC, aspirin, and clopidogrel (Class IIa; LOE C) Dual therapy of OAC, and clopidogrel (Class IIb; LOE C)† † selected pts. at high bleeding risk and low risk of stent thrombosis/recurrent ischemic events Lip GY et al. Eur Heart J 2014;35:3155-79

PIONEER AF-PCI trial Day Clinically significant bleeding (%) MACE (%) Group 1: rivaroxaban 15 mg OD + P2Y12 inhibitor; Group 2: rivaroxaban 2.5 mg BID + DAPT Group 3: adjusted-dose VKA (INR 2.0-3.0) + DAPT Day Clinically significant bleeding (%) MACE (%) Group 1 vs. 3: HR 0.59 (95% CI, 0.47–0.76); p<0.001 Group 2 vs. 3: HR 0.63 (95% CI, 0.50–0.80); p<0.001 Group 1 vs. 3: HR 1.08 (95% CI, 0.69–1.68); p=0.75 Group 2 vs. 3: HR 0.93 (95% CI, 0.59–1.48); p=0.76 Gibson CM et al. N Engl J Med 2016;375:2423-34

PIONEER AF-PCI trial: main limitations 1. individual efficacy end-points comparable among treatment Groups 2. rivaroxaban 15 mg OD dose not approved for clinical use 3. stroke rate significantly higher in Group 2 vs. 3 (when DAPT given for 6 mos.) 4. imbalance in pts. characteristics across treatment Groups 5. stent thrombosis not adjudicated by core laboratory Gibson CM et al. N Engl J Med 2016;375:2423-34

2014 ESC/EACTS guidelines on myocardial revascularization Recommendations Class Level In patients with ACS and atrial fibrillation ….. triple therapy of (N)OAC and ASA (75-100 mg/day) and clopidogrel 75 mg/day should be considered ….. IIa C Dual therapy of (N)OAC and clopidogrel 75 mg/day may be considered as an alternative to initial triple therapy in selected patients. IIb B Adapted from Windecker S et al. Eur Heart J 2014;35:2541-619

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) Incidence of ischemic stroke + MI + vascular death CAPRIE Steering Committee. Lancet 1996;348:1329-39

Prasugrel Loading Dose Prasugrel Maintenance Doses 100 * * * * * 90 * * * * * * * 80 ‡ ‡ ‡ † Clopidogrel 600 mg/75 mg 300 mg/75 mg Prasugrel 60 mg/10 mg 70 ‡ * 60 IPA % (20 mM ADP) 50 † 40 30 * p<0.001 Prasugrel vs Clopidogrel † p<0.05 Clopidogrel 600 mg vs 300 mg ‡ p<0.001 Clopidogrel 600 mg vs 300 mg 20 10 Pre-dose IPA Data are expressed as mean ± SEM -10 0.25 0.5 1 2 4 6 2 3 4 5 6 7 8 9 Time Day 1 (hours) Days Payne CD et al. J Cardiovasc Pharmacol 2007;50:555-62

Wafarin and ticagrelor vs. triple therapy after ACS Braun OÖ et al. Thromb Res 2015;135:26-30

Ongoing trials on PCI in AF RE-DUAL PCI ENTRUST AF-PCI AUGUSTUS Dabigatran 110 mg BID + P2Y12 inhibitor * Dabigatran 150 mg BID + Warfarin + + ASA Edoxaban 60/30 mg + P2Y12 inhibitor ** Warfarin + P2Y12 inhibitor ** + ASA Warfarin + P2Y12 inhibitor** P2Y12 inhibitor ** + ASA Apixaban 5/2.5 mg BID + * clopidogrel/ticagrelor; ** clopidogrel/prasugrel/ticagrelor

Conclusioni Nel paziente con fibrillazione atriale sottoposto a PCI: il regime antitrombotico generalmente raccomandato è triplice terapia * durante triplice terapia, vanno attuate misure per contenere rischio emorragico può essere considerata in casi selezionati duplice terapia ** si attendono risultati di studi in corso circa possibili ulteriori regimi antitrombotici * warfarin/NAO + aspirina + clopidogrel ** warfarin/NAO + clopidogrel