ESC CONGRESS HIGHLIGHTS ISCHEMIC HEART DISEASE Francesco Cosentino (Stockholm, S) Declaration of Interest Advisory Board/Speaker: AstraZeneca, Roche, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Abbott, Novartis, Pfizer, Bayer.
Guideline Adherence in NSTEMI 100 95 90 85 80 75 70 Aspirin B-Blocker P2Y12 inhibitor Statin Angiogram ACE/ARB 65 60 GRACE Lowest (<70) GRACE Low (71-87) GRACE Intermediate - high (>87) 389,057 pts., UK National Heart Attack Registry O. Bebb (Leeds, UK) FP 3821
Guideline Adherence in NSTEMI Adjusted time-varying mortality rate by GRACE risk and receipt of care HR 1 year 1.70 (1.59-1.82) 5 years 1.75 (1.40-2.19) 8 years 1.69 (1.29-2.22) O. Bebb (Leeds, UK) FP 3821
ANTARCTIC Design R n=442 pts. n=435 pts. Group 1 Conventional Arm: Prasugrel 5 mg No monitoring Group 2 Monitoring Arm: Prasugrel 5 mg 1 st assessment : Verifynow P2Y 12 : 2 weeks ± 2 d PRU 208 85<PRU<208 PRU 85 Prasugrel 10 mg/day Prasugrel 5 mg Clopidogrel 75 mg/day 2 nd assessment and adjustment: Verifynow P2Y 12 : 2 weeks ± 2 d Primary end point (net clinical benefit) over 12 months G. Montalescot (Paris, FR) FP 7011
ANTARCTIC Results EP #2 CV death, MI, stroke, stent thrombosis, urgent revascularization Conventional group Monitoring group EP #1 CV death, MI, stroke, stent thrombosis, urgent revascularization or BARC 2, 3 or 5 Conventional group Monitoring group EP #2 BARC 2, 3 or 5 Conventional group Monitoring group G. Montalescot (Paris, FR) FP 7011
ANTARCTIC Conclusions Largest randomized PCI study in the elderly Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an ACS does not improve their clinical outcomes (ischemic, bleeding or net clinical benefit) Platelet reactivity is at best a modifiable marker of risk ESC guidelines still recommend (class IIb, LOE C) platelet function monitoring in high risk situations: ANTARCTIC does not support this recommendation G. Montalescot (Paris, FR) FP 7011
NACIAM Trial The early use of high-dose N-acetylcysteine (NAC) with low-dose glyceryl trinitrate (GTN) in STEMI: a pilot study NAC Interaction? Increased ROS Scavenging NAD(P)H oxidase GTN NO Dinitrates HOCl H 2 O 2 O 2 - release Potentiation cgmp sgc activation Oxidative stress Reperfusion injury Vasodilatation Platelet aggregation Inflammation Tissue reperfusion Potential Infarct size S. Pasupathy (Adelaide, AU) FP 7127
NACIAM Trial Consort diagram Screened (141) Ineligible (9) Randomised (132) NAC (65) Placebo (67) Exclusions (12) Exclusions (8) Study inclusion (53) Study inclusion (59) No MRI (16) No MRI (21) Early MRI: 37 Late MRI: 26 Early MRI: 38 Late MRI: 29 S. Pasupathy (Adelaide, AU) FP 7127
Area At Risk (%) Infarct size (%) NACIAM Trial Results: area at risk and infarct size 50 40 30 20 10 50 40 30 20 10 0 0 Placebo NAC Placebo NAC 23 (18, 31) 25 (17, 37) P=0.76 16.5 (10, 24) 11 (4, 16) P=0.02 S. Pasupathy (Adelaide, AU) FP 7127
NACIAM Trial Results: MRI parameters Placebo (38) NAC (37) P Myocardial Salvage 27% (14%, 41%) 60% (37%, 79%) 0.001 Anterior Infarct 39% 35% 0.81 Microvascular obstruction 1.1 ± 1.8 0.95 ± 1.8 0.66 Transmural infarct 79% 54% 0.02 Infarct size at late MRI 10% (7%, 15%) 5% (1%, 12%) 0.02 S. Pasupathy (Adelaide, AU) FP 7127
NACIAM Trial Results: effect of total ischemia time Treatment (F=9.4, p<0.01), Time* Treatment (F=4.8, p<0.01) S. Pasupathy (Adelaide, AU) FP 7127
Interventional Cardiology NORSTENT: drug-eluting vs. bare metal stents PRAGUE-18: ticagrelor vs. prasugrel in STEMI
NORSTENT: drug-eluting vs. bare metal stents Design Main enrolment criteria Multicenter RCT in Norway 9013 patients (73 % of the eligible) Investigator initiated Funded by not-for-profit organizations Inclusion period 2008-2011 5 years follow-up (median) Stable CAD or ACS All lesions may be treated with DES only or BMS only No previous stent No bifurcation lesion requiring 2-stent technique No intolerance or contraindications to DAPT No indication for anticoagulation K. H. Bønaa, (Trondheim, NO), FP 5713
Type of Stents Used NORSTENT DES group BMS group Promus 67% Xience 16% Endeavor Resolute 12% Other 5% Driver 43% Integrity 22% Liberte 18% Multilink Vision 9% Other 8% 95% newer generation DES K. H. Bønaa, (Trondheim, NO), FP 5713
PRIMARY EP Death and Nonfatal Spontaneous MI NORSTENT HR 0.98 P=0.66 K. H. Bønaa, (Trondheim, NO), FP 5713
All Cause Mortality NORSTENT HR 1.10 P=0.22 K. H. Bønaa, (Trondheim, NO), FP 5713
Any Revascularization NORSTENT HR 0.76 P<0.001 6 year rates: DES 16.5 % BMS 19.8 % ARR 3.3%, NNT 30 K. H. Bønaa, (Trondheim, NO), FP 5713
Definite stent thrombosis - ARC NORSTENT HR 0.64 P=0.0498 6 year rates: DES 0.8 % BMS 1.2 % ARR 0.4%, NNT 250 K. H. Bønaa, (Trondheim, NO), FP 5713
PRAGUE-18: ticagrelor vs. prasugrel in STEMI Prasugrel switched to clopidogrel before day 7: n = 89 (14%) Prasugrel n = 634 Prasugrel continued beyond day 30 or untill death: n = 458 (72%) R Randomized patients: n = 1230 Prasugrel switched to clopidogrel between days 7-30: n = 87 (14%) Ticagrelor switched to clopidogrel before day 7: n = 112 (19%) Ticagrelor n = 596 Ticagrelor continued beyond day 30 or untill death: n = 367 (61%) Ticagrelor switched to clopidogrel between days 7-30: n = 117 (20%) Study terminated earlier (planned 2500 patients) for slow enrolment and futility Allocated P2Y12 inhibitor discontinued within 7 and 30 days in 16% and 33% of the patients, respectively P. WIDIMSKY, (Prague, CZ), FP 5028
Primary endpoint PRIMARY ENDPOINT (7 DAYS) PRAGUE-18 Death, re-infarction, stroke, major bleeding, urgent IRA revascularization 0,05 Ticagrelor 0,04 Prasugrel 0,03 0,02 0,01 P=0.935 (log rank test) 0 0 1 2 3 4 5 6 7 Time (days) P. WIDIMSKY, (Prague, CZ), FP 5028
Key secondary endpoint KEY SECONDARY ENDPOINT (30 DAYS) CIRCULATION PRAGUE-18 CV Death, non-fatal MI, or stroke 0,05 0,04 0,03 Prasugrel 0,02 Ticagrelor 0,01 0 0 5 10 15 20 25 30 Time (days) P. WIDIMSKY, (Prague, CZ), FP 5028
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