ISCHEMIC HEART DISEASE

Transcription

1 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.

2 Guideline Adherence in NSTEMI Aspirin B-Blocker P2Y12 inhibitor Statin Angiogram ACE/ARB 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

3 Guideline Adherence in NSTEMI Adjusted time-varying mortality rate by GRACE risk and receipt of care HR 1 year 1.70 ( ) 5 years 1.75 ( ) 8 years 1.69 ( ) O. Bebb (Leeds, UK) FP 3821

4 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 <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

5 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

6 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

7 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

8 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

9 Area At Risk (%) Infarct size (%) NACIAM Trial Results: area at risk and infarct size Placebo NAC Placebo NAC 23 (18, 31) 25 (17, 37) P= (10, 24) 11 (4, 16) P=0.02 S. Pasupathy (Adelaide, AU) FP 7127

10 NACIAM Trial Results: MRI parameters Placebo (38) NAC (37) P Myocardial Salvage 27% (14%, 41%) 60% (37%, 79%) Anterior Infarct 39% 35% 0.81 Microvascular obstruction 1.1 ± ± 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

11 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

12 Interventional Cardiology NORSTENT: drug-eluting vs. bare metal stents PRAGUE-18: ticagrelor vs. prasugrel in STEMI

13 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 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

14 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

15 PRIMARY EP Death and Nonfatal Spontaneous MI NORSTENT HR 0.98 P=0.66 K. H. Bønaa, (Trondheim, NO), FP 5713

16 All Cause Mortality NORSTENT HR 1.10 P=0.22 K. H. Bønaa, (Trondheim, NO), FP 5713

17 Any Revascularization NORSTENT HR 0.76 P< year rates: DES 16.5 % BMS 19.8 % ARR 3.3%, NNT 30 K. H. Bønaa, (Trondheim, NO), FP 5713

18 Definite stent thrombosis - ARC NORSTENT HR 0.64 P= year rates: DES 0.8 % BMS 1.2 % ARR 0.4%, NNT 250 K. H. Bønaa, (Trondheim, NO), FP 5713

19 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

20 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) Time (days) P. WIDIMSKY, (Prague, CZ), FP 5028

21 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, Time (days) P. WIDIMSKY, (Prague, CZ), FP 5028

22 THANK YOU!