Tiêu chuẩn mới và triển vọng can thiệp động mạch vành cấp trong tương lai

Future Directions in Treatment of STEMI Vietnam Heart Association Meeting Danang October 12, 2014 Thach Nguyen MD FACC FSCAI Director of Cardiology St Mary Medical Center, Hobart IN P2Y12 inhibitor for CAD • Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, Naganuma H, Siegbahn A, Wallentin L Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease Eur Heart J 2006;27:1166–1173 • Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T,Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: theONSET/OFFSET study Circulation 2009;120:2577–2585 • Substudy of 7544 STEMI patients with planned PCI from the PLATO Trial • Ticagrelor was superior to clopidogrel – – Primary endpoint (composite of MI, stroke, CV death) Secondary endpoints (MI alone, total mortality, stent thrombosis) • Major bleeding not increased • Circulation 2010;122:2131-2141 Pre-hospital ticagrelor ? • ATLANTIC trial (N Engl J Med 2014;371:101627) 1862 STEMI patients with ambulance vs cath lab ticagrelor • Ambulance group treated 31 minutes earlier • No difference in pre-PCI coronary reperfusion (by ECG or TIMI flow) • Stent thrombosis reduced • No increased risk of bleeding ACC/AHA 2013 STEMI Guidelines CLASS I ESC 2012 STEMI Guidelines Anticoagulant for PCI • In the CURE trial, the residual risk for death, MI, or stroke after 12 months of treatment with clopidogrel together with aspirin was approximately 10% In the TRITON and PLATO trials, with new and more potent antiplatelet agents combined with aspirin, there was the same residual risk As the mechanism of ACS is due to superimposed thrombus, the hypothesis is that anticoagulants might improve the CV outcomes in patients with a recent ACS In early 2000, this hypothesis was tested in the WARIS trial with warfarin (REF: Hurlen NEJM 2002; 347: 969-974) • The results showed that warfarin could decrease MI and re-infarction however with a higher risk of bleeding Recently, this hypothesis is tested again with low-dose of rivaroxaban, an inhibitor of factor Xa on a background of clopidodrel in the ATLAS ACS TIMI 51 trial Statin for CAD and STEMI The LAPLACE-2 Trial: A Phase 3, Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia Jennifer G Robinson,1 Bettina S Nedergaard,2 William J Rogers,3 Jonathan Fialkow,4 Joel M Neutel,5 David Ramstad,6 Ransi Somaratne,7 Jason C Legg,7 Patric Nelson,7 Robert Scott,7 Scott M Wasserman,7 and Robert Weiss,8 for the LAPLACE-2 Investigators 1College of Public Health, University of Iowa, Iowa City, IA, USA; 2Center for Clinical and Basic Research, Aalborg, Denmark; 3University of Alabama Medical Center, Birmingham, AL, USA; 4Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA; 5Orange County Research Center, Tustin, CA, USA; 6Hampton Roads Center for Clinical Research, Suffolk, VA, USA; 7Amgen Inc., Thousand Oaks, CA, USA; 8Maine Research Associates, Auburn, ME, USA March 30, 2014, Late-Breaking Clinical Trials Session 402 American College of Cardiology, Washington DC LAPLACE-2: Baseline Lipids Any Statin + Placebo (N = 558) Atorvastatin + Ezetimibe (N = 221) Any Statin + Evolocumab (N = 1117) LDL-C,a mg/dL, mean (SD) 108 (40) 109 (37) 110 (42) ApoB, g/L, mean (SD) 88 (25) 90 (25) 90 (27) TG, mg/dL, mean (SD) 129 (66) 136 (77) 137 (82) HDL-C, mg/dL, mean (SD) 55 (17) 52 (15) 53 (16) Lp(a), mg/dL, mean (SD) 86 (100) 92 (104) 91 (113) PCSK9, ng/mL, mean (SD) 353 (114) 351 (112) 355 (111) Baseline characteristics were collected at randomization to statin aDetermined by the Friedewald formula with reflexive testing via preparative ultracentrifugation when calculated LDL-C was < 40 mg/dL or triglycerides were > 400 mg/dL LDL-C, low-density lipoprotein cholesterol; ApoB, apolipoprotein B; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; Lp(a), lipoprotein (a); PCSK9, 31 proprotein convertase subtilisin/kexin type LAPLACE-2: LDL-C Response at Mean of Weeks 10 and 12 Mean Percent Change from Baseline in LDL−C Evolocumab Q2W & QM: 63 to 75% reductions in LDL-C versus placebo Ezetimibe: 19 to 32% reductions in LDL-C versus placebo Atorvastatin 80 mg Placebo Q2W Placebo QM Rosuvastatin 40 mg Atorvastatin 10 mg Ezetimibe QD + Placebo Q2W Ezetimibe QD + Placebo QM All treatment32 differences versus placebo and ezetimibe were statistically significant (P[...]... 6Hampton Roads Center for Clinical Research, Suffolk, VA, USA; 7Amgen Inc., Thousand Oaks, CA, USA; 8Maine Research Associates, Auburn, ME, USA March 30, 2014, Late-Breaking Clinical Trials Session 402 American College of Cardiology, Washington DC LAPLACE-2: Baseline Lipids Any Statin + Placebo (N = 558) Atorvastatin + Ezetimibe (N = 221) Any Statin + Evolocumab (N = 1117) LDL-C,a mg/dL, mean (SD) 108 (40)... mg Placebo Q2W Placebo QM Rosuvastatin 40 mg Atorvastatin 10 mg Ezetimibe QD + Placebo Q2W Ezetimibe QD + Placebo QM All treatment32 differences versus placebo and ezetimibe were statistically significant (P