1. 比伐卢定在 STEMI 中的应用价值 王乐丰 首都医科大学附属北京朝阳医院心脏中心

2. Goals of STEMI PCI Establish reperfusion of IRA ASAP Limit complications Limit costs Achieve excellent long term outcomes (MACE)

11. HORIZONS AMI Trial  Independent Predictors of Acute Stent Thrombosis Dangas et al, ACC 2009 Factor HR for stent thrombosis P Value Pre-PCI TIMI flow 0-16.100.01 Lesion ulceration4.800.01 Bivalirudin (vs heparin + GP IIb/IIIa) 4.650.005 Number of stents1.500.02 Prerandomization heparin0.270.002

16. How about recent studies?

35. BivalirudinHeparin n%n MACE798.7 % v 5.7 %52 Absolute risk increase = 3.0% (95% CI 0.6, 5.4) Relative risk = 1.52 (95% CI 1.1 – 2.1) P=0.01

36.  Event curve shows first event experienced

43. HEAT PPCI  STEMI with Primary PCI  Primary PCI  Bivalirudin  0.75 mg/kg +  1.75 mg/kg/h  Unfractionated Heparin  70 U/kg  ‘Bail-out’ GP IIb/IIIa  N=1829  15%  89 % Pras. or Ticag.  81 % Radial  Shahzad. Lancet.2014; doi:10.1016/S0140-6736(14)60924-7

44. HEAT PPCI: Major Issues for Discussion  Approval given by UK regulatory authorities  Informed consent obtained several days after randomization. Can informed consent be obtained in the setting of an acute STEMI?  “All comers”  99% of patients with STEMI  Unexpectedly high rate of acute (<24 hours) stent thrombosis in bivalirudin-treated patients.  Unlike HORIZONS AMI, there was no late catch-up of stent thrombosis  Effect of prasugrel/ticagrelor?  Shahzad. Lancet.2014; doi:10.1016/S0140- 6736(14)60924-7

45.  Schulz.Eur. Heart J.2014;35:2285-2294 BRAVE 4 Trial  STEMI < 12 HOURS  Primary PCI  Bivalirudin  0.75 mg/kg +  1.75 mg/kg/h  +  Prasugrel  Unfractionated Heparin  70 - 100 U/kg  +  Clopidogrel  ‘Bail-out’ GP IIb/IIIa  N=548  4.5%  95 % Prasugrel

46. NAPLES III Trial  Femoral PCI  +  Biomarker Negative  +  High Risk for Bleeding  Bivalirudin  0.75 mg/kg +  1.75 mg/kg/h  (ACT-guided)  Unfractionated Heparin  70 U/kg  (ACT-guided)  ‘Bail-out’ GP IIb/IIIa  N=837  0.9%  ACC 2014

47. Horizons-Primary PCI Cohort (N=3,340; 92.7%) 30-day Event rates  RR = 0.99 [0.75, 1.32]  P sup = 1.00  RR = 0.59 [0.46, 0.77]  P NI ≤ 0.0001  P sup ≤ 0.0001  RR = 0.75 [0.62, 0.92]  P NI ≤ 0.0001  P sup = 0.005  *Not related to CABG  **MACE = All cause death, reinfarction, ischemic TVR or stroke  Heparin + GPIIb/IIIa inhibitor (n=1662)  Bivalirudin monotherapy (n=1678)  Net adverse clinical Major bleeding* MACE**  events %%  12.3  9.2  8.6  5.1  5.5  5.4

48.  Number at risk  Bivalirudin 1678 1647 16401635 1632 1620 1563  Heparin + GPIIb/IIIa 1662 1631 16151604 1598 1583 1512  Death (%)  Time in days  1.8%  Heparin + GPIIb/IIIa inhibitor (n=1662)  Bivalirudin monotherapy (n=1678)  0.2%  0.1%  Cardiac  Non cardiac  30 Day Mortality: PCI Cohort  2.8%  HR [95%CI] = 0.63 [0.40, 0.99]  P=0.049

49. HORIZONS AMI Trial: Stent Thrombosis (N=3,124) UFH + GP IIb/IIIa (N=1553)Bivalirudin(N=1571)PValue ARC definite or probable*1.9%2.5%0.33 - definite1.4%2.2%0.11 - probable0.5%0.3%0.26 - acute (≤24 hrs)0.3%1.3%0.0009 - subacute (>24 hrs – 30d)1.7%1.2%0.30  *Protocol definition of stent thrombosis, CEC adjudicated

50. HORIZONS AMI Trial  Effect of Prerandomization Heparin on Incidence of Acute Stent Thrombosis Dangas et al, ACC 2009 Group Prerandomizatio n heparin (%) No prerandomization heparin (%) HR [95% CI] P Value Bivalirudin0.92.63.070.006 Heparin + GP IIb/IIIa blocker 0.10.89.640.02

51. HORIZONS AMI Trial  Independent Predictors of Subacute Stent Thrombosis Dangas et al, ACC 2009 Factor HR for stent thrombosis P Value Insulin-treated diabetics4.430.0002 History of CHF4.160.003 Pre-PCI TIMI flow 0-12.210.04 Final TIMI flow 0-13.720.03 Stent/lesion-length ratio1.44<0.0001 Clopidogrel loading dose 600 mg (vs. 300 mg) 0.490.01

64.  S. Cassesse et al. 2014 EuroIntervention. On Line  Bivalirudin Versus Heparin:  Choosing Bleeding or Stent Thrombosis as Your Complication Preference?

65. Bivalirudin vs Heparin Strategies: How Much GPI Will You Use? GP IIb/IIIa inhibitor use Hazard ratio for major bleeding 95% CIp Predominantly in heparin arm (HORIZONS, EUROMAX) 0.530.47–0.61<0.0001 Provisional in both arms ( HEAT, NAPLES 3 ) 0.780.51–1.190.25 Planned in both arms (ACUITY, TENACITY) 1.070.87–1.310.53 End pointHazard ratio95% CIp MACE1.091.01–1.170.02 MI1.121.03–1.23 < 0.05 Ischemia-driven revascularization 1.160.997–1.34 NS Mortality0.990.82–1.18 Stent thrombosis 1.381.09–1.740.007 Major bleeding 0.620.49–0.78<0.0001  All Bivalirdudin vs Heparin STEMI trials: The Tradeoff Argument of 2008-2013  Bivalirudin versus Heparin Alone:  Benefit Stratified by GPI Use  2014  M. Sabatine et al, Lancet August 2014

66. Take home message In comparison with the currently used standard regimen of heparin, administration of bivalirudindoes not reduce mortality in patients undergoing PCI However, bivalirudinas compared to heparin appears to reduce the risk of major bleeding at the expense of a higher risk of acute stent thrombosis

70. 谢谢！