Case presentation • • • • • • • • • 79 years- old lady BMI 22 Hypertension Dyslipidemia PCI (DES LAD Jan 2015) High risk UA- TIMI HR 70 BP 120/55 RR 18 T 36.80C SpO2 98% (room air) • On regular Rx: – – – – – – – – – Losartan 50mg qd Amlodipin 5mg qd ASA 81mg qd Ticagrelor 90 bid Metoprolol succinate 25mg qd ISMN 60mg qd Furosemide/ Spironolactone 10/25mg qd Rosuvastatin 20mg qd Trimetazidine 35mg bid Blood investigations • • • • • • • • WBC 10 k/uL (N: 52%) PLT 242 K/uL Hs-CRP 0.8 mg/L HGB 12 g/dL Creatinin 92 mmol/l eGFR 39ml/ph/1.73m2 AST 28 ALT 26 U/L TSH 2.5 mUI/L • • • • Cholesterol HDL-C LDL-C TG • NT-proBNP • Hs-TnT 3.5 1.1 2.2 2.5 mmol/L 364pg/ml 14 – 13 pg/ml On admission ECG Sinus rhythm 85 bpm, normal QRS axis and PR interval ST-T depression 1-2 mm in DI, DII, V1-V4 Imaging findings Echocardiography • LVEF 65% • No chamber dilatation • No RWMA; No thrombus • MR (+) TR (+) • S PAP 25mmHg • TAPSE 20 HIGH RISK UNSTABLE ANGINA (TIMI SCORE 5) HYPERTENSION – DYSLIPIDEMIA – CHRONIC KIDNEY DISEASE Plan for early invasive strategy Coronary angiogram Patent LAD stent No ISR Diffused LCx (small vessel) Total occlusion RCA For RCA CTO intervention RCA PCI • Complex PCI with overlapping DES implantation (2.5x21mm, 2.75x38mm, 3x38mm) • TIMI flow of RCA post stenting Post PCI- CCU f/u Day 1-2 • Felt better • No chest pain • Hemodynamic stability • HR: 100- 70bpm • BP: 110/50mmHg Day • Palpitation • Monitor: paroxysmal fast AF (110-120 bpm) • BP: 110/50 mmHg • SpO2 96% Echo: LVEF 50% • CHA2DS2-VASc : • HAS-BLED: Anti-thrombotic therapy for ACS/PCI plus AF AF Anticoagulant Rx • Essential to prevent thromboembolic events • Superior to single or dual antiplatelet therapy • Life long ACS/PCI DAPT Rx • Superior to ASA alone in ACS • Essential to prevent stent thrombosis post PCI • ≥12 months Lip et al Eur Heart J 2014;35:3155-3179 AF and ACS/PCI Triple Rx • By what medications? • For how long? • How much data we have? Highest bleeding rate with triple therapy Danish cohort of 82854 patients with AF followed for an average of 3.3 years Significant bleeding rate with triple therapy was 15.7 per 100 patient-year Hansen et al Arch Intern Med 2010;170:1433-1441 Risk of stroke according to CHA2DS2-VASc CHA2DS2-VASc criteria Score Congestive heart failure/ left ventricular dysfunction Hypertension Age 75 years Diabetes mellitus Stroke/transient ischaemic attack/TE Vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque) Age 65–74 years Sex category (i.e female gender) Total score N Adjusted stroke rate (%/year)* 0.0 422 1.3 1230 2.2 1730 3.2 1718 4.0 1159 6.7 679 9.8 294 9.6 82 6.7 14 15.2 *Adjusted for warfarin use Theoretical rates without therapy; assuming that warfarin provides a 64% reduction in stroke risk, based on Hart RG et al 2007 TE = thromboembolism Lip G et al Chest 2010;137:263–72; Lip G et al Stroke 2010;41:2731–8; ESC guidelines: Camm J et al Eur Heart J 2010;31:2369–429; Hart RG et al Ann Intern Med 2007;146:857–67 OBJECTIVES …Whether shortening the duration of clopidogrel therapy from months to weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC METHODS… Randomized, open-label trial 614 patients receiving 6week clopidogrel therapy (n= 307) or 6-month clopidogrel therapy (n= 307) The primary endpoint was a composite of death, MI, definite ST, stroke, or TIMI major bleeding at months J Am Coll Cardiol 2015;65:1619–29 Main findings from ISAR- TRIPLE (A)primary endpoint (cumulative incidence of death, myocardial infarction, stent thrombosis, stroke or TIMI major bleeding) (B)secondary ischemic endpoint (cardiac death, myocardial infarction, stent thrombosis, or ischemic stroke) J Am Coll Cardiol 2015;65:1619–29 Bleeding in ISAR- TRIPLE  No difference in TIMI major bleeding between the groups (5.3%vs 4.0%; HR: 1.35; 95% CI: 0.64 to 2.84; p= 0.44)  Any BARC bleeding occurred in 114 patients in the 6-week group and 122 patients in the 6-month group (HR:0.94;95%CI:0.73to1.21; p= 0.63)  Intracranial bleeding frequency was low J Am Coll Cardiol 2015;65:1619–29 Compare efficacy and safety outcomes of triple therapy vs dual therapy (clopidogrel with aspirin or OAC) Hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation 16 eligible trials including 9185 patients Clin Cardiol 38, 8, 499–509 (March 2015) Main findings from meta-analysis Triple therapy has a similar risk of MACE compared with dual therapy (OR: 1.06, 95% CI: 0.82-1.39, P = 0.65) The risk of all-cause mortality, MI, and ST did not significantly differ between the triple and dual therapy groups  all-cause mortality, OR: 0.98, 95% CI: 0.76-1.27,P = 0.89  MI, OR: 1.01, 95% CI: 0.77-1.31, P = 0.97  ST, OR: 0.91, 95% CI: 0.49-1.69, P = 0.75 Clin Cardiol 38, 8, 499–509 (March 2015) Less ischemic stroke and more bleeding with triple therapy Triple therapy was associated with a significantly lower incidence of ischemic stroke (OR: 0.57, 95% CI: 0.35-0.94,P = 0.03) Significantly increased major bleeding in the triple therapy group (OR: 1.52, 95% CI: 1.11-2.10, P = 0.01), as well as minor bleeding (OR: 1.59, 95% CI: 1.05-2.42, P =0.03) Conclusion  In patients taking oral anticoagulants and undergoingPCI , OAC plus clopidogrel was associated with at least similar efficacy and safety outcomes compared with triple therapy  Triple therapy regimens could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events Clin Cardiol 38, 8, 499–509 (March 2015) Herz (July 2015),DOI 10.1007/s00059-015-4325-0 23 clinical trials comprised 22,212 participants TT was more efficacious than DT (DAPT or OAC + single APT) in reducing MACE/stroke (RR =0.76, 95% CI: 0.70–0.83; p< 0.00001 & RR = 0.67,95% CI: 0.59–0.75; p< 0.00001, respectively) There was a significant reduction in all-cause death in the TT compared with the DT regimen (RR = 0.64, 95 % CI: 0.56–0.73; p < 0.00001& RR = 0.48, 95 % CI: 0.39–0.58; p < 0.00001,respectively) More major bleeding in patients receiving TT compared with DAPT (p < 0.00001), but… No difference between those receiving TT and OAC + single antiplatelet agent (RR = 0.96; 95 % CI: 0.75–1.21; p = 0.71) Herz (July 2015),DOI 10.1007/s00059-015-4325-0 No differences in MACE/ Stroke & All- cause death between TT and OAC+ clopidogrel Herz (July 2015),DOI 10.1007/s00059-015-4325-0 Management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing PCI or valve interventions: a joint consensus document European Heart Journal doi:10.1093/eurheartj/ehu298 (July 2014) 2015 ESC guidelines for the management of ACS in patients presenting without persistent ST-segment elevation European Heart Journaldoi:10.1093/eurheartj/ehv320 (August 2015) Guidance for combination therapy in patients with AF and ACS Class In general, the period of triple therapy should be as short as possible, followed by OAC plus a single antiplatelet therapy (clopidogrel 75 mg/d, or as an alternative, ASA 75–100 mg/d) Long-term antithrombotic therapy with OAC (beyond 12 months) is recommended in all patients Where a NOAC is used in combination with clopidogrel and/or low-dose ASA, the lower tested dose for stroke prevention in AF may be considered Level General recommendation I B IIb C Lip GYH et al Eur Heart J 2014;doi:10.1093/eurheartj/ehu298 ESC 2015, London, UK XANTUS: Low rates of Bleeding and Stroke in a Real-World Prospective, Observational study of Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation To collect real-life data on adverse events in patients with nonvalvular AF treated with rivaroxaban to determine its safety profile across the broad range of patient risk profiles encountered in routine clinical practice Primary outcomes: major bleeding, all-cause mortality, any other adverse events XANTUS results N= 6784 @ 311 centers Mean age was 71.5 Hx MI 10.1% Mean CHADS2 & CHA2DSVASc scores were 2.0 & 3.4 Mean treatment duration was 329 days Major bleeding occurred in 128 patients (2.1 events/100 patient-years) 118 (1.9 events/ 100 patient-years) died 43 (0.7 events/ 100 patient-years) suffered a stroke European Heart Journal doi:10.1093/eurheartj/ehv466 Our patient treatment & Conclusions CHA2DS2-VASc= with High bleeding risk (HAS-BLED = 3)  [Clopidogrel 75 mg + Aspirin 100 mg + Xarelto 15 mg daily] for weeks (finished without any bleeding complication) [Clopidogrel 75 mg + Xarelto 15 mg daily ] up to 12 months after PCI procedure (September 2016)- Xarelto for life after that AF plus ACS/PCI: challenge clinical scenario that need careful assessment for risk of embolic event (CHA2DS2-VASc score) and bleeding (HAS-BLED) to have appropriate anti-thrombotic therapy Thank you for your attention! [...]... (beyond 12 months) is recommended in all patients 3 Where a NOAC is used in combination with clopidogrel and/or low-dose ASA, the lower tested dose for stroke prevention in AF may be considered Level General recommendation I B IIb C Lip GYH et al Eur Heart J 2014;doi:10.1093/eurheartj/ehu298 ESC 2015, London, UK XANTUS: Low rates of Bleeding and Stroke in a Real-World Prospective, Observational study of... year Lower mortality rate in double versus triple therapy Lancet 2013; 381: 1107–15 OBJECTIVES …Whether shortening the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC METHODS… Randomized, open-label trial 614 patients receiving 6week clopidogrel therapy (n= 307) or 6-month... 6-month clopidogrel therapy (n= 307) The primary endpoint was a composite of death, MI, definite ST, stroke, or TIMI major bleeding at 9 months J Am Coll Cardiol 2015;65:1619–29 Main findings from ISAR- TRIPLE (A)primary endpoint (cumulative incidence of death, myocardial infarction, stent thrombosis, stroke or TIMI major bleeding) (B)secondary ischemic endpoint (cardiac death, myocardial infarction, stent... 1 Compare efficacy and safety outcomes of triple therapy vs dual therapy (clopidogrel with aspirin or OAC) 2 Hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation 16 eligible trials including 9185 patients Clin Cardiol 38, 8, 499–509 (March 2015) Main findings from meta-analysis 1 Triple therapy has a similar risk of MACE compared... safety outcomes compared with triple therapy  Triple therapy regimens could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events Clin Cardiol 38, 8, 499–509 (March 2015) Herz (July 2015),DOI 10.1007/s00059-015-4325-0 1 23 clinical trials comprised 22,212 participants 2 TT was more efficacious than DT (DAPT or OAC + single APT) in reducing MACE/stroke (RR... without persistent ST-segment elevation European Heart Journaldoi:10.1093/eurheartj/ehv320 (August 2015) Guidance for combination therapy in patients with AF and ACS Class 1 In general, the period of triple therapy should be as short as possible, followed by OAC plus a single antiplatelet therapy (clopidogrel 75 mg/d, or as an alternative, ASA 75–100 mg/d) 2 Long-term antithrombotic therapy with OAC... Methods Open-label, multi-centre, randomised, controlled trial in 15 centers in Belgium and the Netherlands  Clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy)  The primary outcome was any bleeding within 1 year of PCI Lancet 2013; 381: 1107–15 WOEST study Primary endpoint : Total number of bleeding events (TIMI) Lancet 2013; 381: 1107–15 WOEST-Secondary and safety endpoints... study of Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation 1 To collect real-life data on adverse events in patients with nonvalvular AF treated with rivaroxaban to determine its safety profile across the broad range of patient risk profiles encountered in routine clinical practice 2 Primary outcomes: major bleeding, all-cause mortality, any other adverse events XANTUS results... Xarelto 15 mg daily] for 4 weeks (finished without any bleeding complication) 2 [Clopidogrel 75 mg + Xarelto 15 mg daily ] up to 12 months after PCI procedure (September 2016)- Xarelto for life after that 3 AF plus ACS/PCI: challenge clinical scenario that need careful assessment for risk of embolic event (CHA2DS2-VASc score) and bleeding (HAS-BLED) to have appropriate anti-thrombotic therapy Thank you... 1 Triple therapy was associated with a significantly lower incidence of ischemic stroke (OR: 0.57, 95% CI: 0.35-0.94,P = 0.03) 2 Significantly increased major bleeding in the triple therapy group (OR: 1.52, 95% CI: 1.11-2.10, P = 0.01), as well as minor bleeding (OR: 1.59, 95% CI: 1.05-2.42, P =0.03) Conclusion  In patients taking oral anticoagulants and undergoingPCI , OAC plus clopidogrel was associated