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HỘI NGHỊ KHOA HỌC TIM MẠCH TOÀN QUỐC 2015 Optimizing treatment for ACS patient with vessel disease & complete heart block Dinh Duc Huy, MD, FSCAI Nguyen Ngo Thanh Phuong, MD Tam Duc Heart Hospital Case presentation • • • • • • • • Mr D C T, 63 years old BMI 24 (H 170cm, BW 70kg) Smoker (+), 50 pack years Hypercholesterolemia (+) HTN (+), DM (+) for 10 years Chest pain sometimes Weakness and fatigue on exertion days before Shortness of breath on admission day Case presentation • • • • • • • • • Alert No neurological sign HR 37 bpm BP 141/47 mmHg RR 20 bpm SpO2 96% Regular S1, S2 Clear lungs No lower limbs edema • • • • • • • • • • • WBC 7.71k/uL HGB 11.7 g/dL PLT 171K/uL Creatinin 222 umol/L, eGFR:27ml/ph/1.73m2 hs-CRP 4.3mg/L AST 41 U/L ALT 25 U/L Cholesterol 2.58 HDL-C 0.72 LDL-C 1.6 TG: 1.74 mmol/L NT proBNP 9330pg/ml hs-TnT 126.4->113.8 pg/ml On admission ECG Monitoring ECG: BAV II intermittent BAV III Imaging findings Chest Xray • CTR: 0.5 • Normal pulmonary vascularity Echocardiography • LVEF 73%; LV42/24mm • No RWMA; No thrombus • Moderate Aortic Stenois • Gd trans Ao= 42/14 mmHg • MR (+) • sPAP 25mmHg Vascular Ultrasound • Carotid: no stenosis • Normal ABI • Lower limbs arteries:  Right: 40-50%% stenosis of midsuperficial femoral artery caused by stable plaque  Left: 50% stenosis & diffuse stenosis after the bifurcation of the popliteal artery Case management DIAGNOSIS:  NSTEMI-HTN- T2DM-CKD  Intermittent BAV II-III TREATMENT:  TPM/PPM?  Coronary angiogram? When?  PCI/CABG before or after PPM?  Anti-platelet therapy? (Pretreatment? Clopidogrel or New drugs [Pasugrel/Ticagrelor] to be combined with Aspirin?) for how long? … The optimal timing of ticagrelor or clopidogrel for patients scheduled for an invasive strategy has not been adequately investigated, no recommendation for or against pretreatment Based on the ACCOAST results, pretreatment with prasugrel is not recommended (TIMI major bleeds were significantly increased in the pretreatment group at days Pretreatment in NSTE-ACS + PCI (RCTs) Bellemain-Appaix A et al BMJ 2014;349:g6269 TRANSLATE ACS Registry: 9251 ACS patients Thienopyridine naive, undergoing PCI- Real life PCI Effron MB et al J Am Coll Cardiol 2014;63(12_S)  Prompt opening of the infarct vessel is often sufficient to reverse new-onset ischaemic conduction disturbances This is especially true for atrioventricular (AV) block in the setting of inferior infarctions  Temporary pacing is indicated for symptomatic lifethreatening bradycardia not resolving after successful reperfusion and after medical treatment in the presence of high-degree AV block and intraventricular conduction defects  Permanent pacing is considered for disturbances that persist beyond the acute phase after the myocardial infarction Recommendations for management of new bundle branch block and atrio-ventricular conduction disorders in ACS Euro Intervention 2014 CURE study- Corner stone for DAPT in ACS: Clopidogrel+ ASA are better than ASA alone PCI Group Placebo (11.4%) 0.12 0.20 CVD/MI/Stroke CV Death, MI, Stroke 0.14 0.10 Clopidogrel (9.3%) 0.08 0.06 0.04 Clopidogrel RR 0.80, p 75, weight < 60kg • Multicenter, double-blind, randomized trial • 18,624 ACS patients • Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loadingdose, 75 mg daily thereafter) Wallentin L et al N Engl J Med 2009;361 15 Ticargrelor 10 Clopidogrel 11.6% 11.2% P= 0,43 HR: 1.04 (95% CI, 0.95–1.13) 0 60 120 180 240 300 Major bleeding in PLATO 360 16 Xuất huyết nặng chung (%) Xuất huyết nặng chung (%) Same major bleeding with Ticagrelor vs Clopidogrel in PLATO study Ticagrelor 14 12 13.4% Clopidogrel 12.6% 10 P= 0,26 HR: 1.07 (95% CI 0.95–1.19 0 60 120 180 240 300 Major bleeding in NSTE-ACS subgroup Lindholm D, et al J Am Coll Cardiol 2013;61(suppl 10):Abstract 901–903 Wallentin L et al N Engl J Med 2009;361:1045–1057 360 PLATO- Bradycardia Events  Holter monitoring during the first week in 2866 patients  Repeated at 30 days in 1991 patients  Higher incidence of ventricular pauses in the 1st week, but not at day 30; pauses were rarely associated with symptoms  No significant difference to the incidence of syncope or pacemaker implantation Wallentin L et al N Engl J Med 2009;361 Methods 7-day cECG recording initiated at the time of randomisation, which was within 24 h of symptom onset, and then repeated at month after randomization during the convalescent phase The principal safety endpoint was the incidence of ventricular pauses lasting at least seconds J Am Coll Cardiol 2011;57:1908–16 cECG Assessment Patient CONSORT Diagram J Am Coll Cardiol 2011;57:1908–16 Arrhythmias at Visit (Week 1) and Visit (Day 30) for All Patients  More ventricular pauses ≥3 s in patients assigned to ticagrelor during the first week (5.8% vs 3.6%; p=0.006)  At month, pauses ≥3 s were less and similar between treatments (2.1% vs 1.7%) J Am Coll Cardiol 2011;57:1908–16 Other findings • Week 1: 70 patients (3.2% ) had pause, 20 (0.6%) had > pauses • month: patients (0.05%) had pause, 17 (0.8%) had > pauses • There is a nocturnal excess of pauses among patients assigned to ticagrelor, with a peak in the frequency of ventricular pauses at night J Am Coll Cardiol 2011;57:1908–16 Study conclusions More patients treated with ticagrelor compared with clopidogrel had ventricular pauses, which were predominantly asymptomatic, sinoatrial nodal in origin, and nocturnal and occurred most frequently in the acute phase of ACS There were no differences between ticagrelor and clopidogrel in the incidence of clinically reported bradycardic adverse events, including syncope, pacemaker placement, and cardiac arrest J Am Coll Cardiol 2011;57:1908–16 Our patient treatment In hospital  Ticargrelor (180 mg loading & 90 mg bd)  ASA 81mg qd  Atorvastatin 20mg qd  Lisinopril 10mg qd  Amlodipine 5mg qd Low dose beta blocker started during follow up Well, so far, months after the index event, no chest pain, no sign and symptoms of HF; ECG maintains normal sinus rhythm DAPT for how long? A 1-year durationof DAPT with clopidogrel was associated with a 26.9% RRR of death, MI or stroke (8.6% vs 11.8%; 95% CI 3.9, 44.4; P= 0.02) vs 1-month DAPT in CREDO trial 2015 ESC guidelines for the management of ACS in patients presenting without persistent STsegment elevation European Heart Journal doi:10.1093/eurheartj/ehv320 Stronger antiplatelet therapy beyond year in prior MI or angiographic-proven CAD European Heart Journal doi:10.1093/eurheartj/ehv377 (August 2015) Conclusions Early invasive strategy for high risk ACS Revascularisation is often sufficient to reverse newonset ischaemic conduction disturbances No clear benefit of pretreatment antiplatelet therapy Treatment with ticagrelor (vs clopidogrel) significantly reduced the rate MACCE without increasing the overall major bleeding or bradycardic adverse events DAPT for 12 months after ACS Need careful assessment of the ischaemic and bleeding risks if plan to prolong DAPT duration Thank you for your attention! [...]... 0.95–1. 13) 0 0 60 120 180 240 30 0 Major bleeding in PLATO 36 0 16 Xuất huyết nặng chung (%) Xuất huyết nặng chung (%) Same major bleeding with Ticagrelor vs Clopidogrel in PLATO study Ticagrelor 14 12 13. 4% Clopidogrel 12.6% 10 8 6 P= 0,26 4 HR: 1.07 (95% CI 0.95–1.19 2 0 0 60 120 180 240 30 0 Major bleeding in NSTE-ACS subgroup 1 Lindholm D, et al J Am Coll Cardiol 20 13; 61(suppl 10):Abstract 901–9 03 2 Wallentin... elevation European Heart Journal doi:10.10 93/ eurheartj/ehv320 Stronger antiplatelet therapy beyond 1 year in prior MI or angiographic-proven CAD European Heart Journal doi:10.10 93/ eurheartj/ehv377 (August 2015) Conclusions 1 Early invasive strategy for high risk ACS 2 Revascularisation is often sufficient to reverse newonset ischaemic conduction disturbances 3 No clear benefit of pretreatment antiplatelet... 2004;110:1202-1208, 200 30 0 Wiviott et al New Eng J Med 2007; 35 7 No benefit with prior stroke, age > 75, weight < 60kg • Multicenter, double-blind, randomized trial • 18,624 ACS patients • Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (30 0-to-600-mg loadingdose, 75 mg daily thereafter) Wallentin L et al N Engl J Med 2009 ;36 1 15 Ticargrelor 10 Clopidogrel 11.6% 11.2% 5 P= 0, 43 HR: 1.04... SYNTAX score NEJM 2009; 36 0: 961-72 CABGvs PCI for patients with three-vessel disease: final 5-year follow up of the SYNTAX trial European Heart Journal doi:10.10 93/ eurheartj/ehu2 13 ConclusionFive-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care Our patient treatment- 3 VD PCI with DES • • •... J Med 2009 ;36 1:1045–1057 36 0 PLATO- Bradycardia Events  Holter monitoring during the first week in 2866 patients  Repeated at 30 days in 1991 patients  Higher incidence of ventricular pauses in the 1st week, but not at day 30 ; pauses were rarely associated with symptoms  No significant difference to the incidence of syncope or pacemaker implantation Wallentin L et al N Engl J Med 2009 ;36 1 Methods... incidence of ventricular pauses lasting at least 3 seconds J Am Coll Cardiol 2011;57:1908–16 cECG Assessment Patient CONSORT Diagram J Am Coll Cardiol 2011;57:1908–16 Arrhythmias at Visit 1 (Week 1) and Visit 2 (Day 30 ) for All Patients  More ventricular pauses 3 s in patients assigned to ticagrelor during the first week (5.8% vs 3. 6%; p=0.006)  At 1 month, pauses 3 s were less and similar between treatments... Clopidogrel (9 .3% ) 0.08 0.06 0.04 Clopidogrel RR 0.80, p 4 pauses • 1 month: 9 patients (0.05%) had 1 pause, 17 (0.8%) had > 4 pauses • There is a nocturnal excess of pauses among patients assigned to ticagrelor, with a peak