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

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

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 Lesion ulceration Bivalirudin (vs heparin + GP IIb/IIIa) Number of stents Prerandomization heparin

How about recent studies?

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

 Event curve shows first event experienced

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: /S (14)

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: /S (14)

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

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

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 ≤  P sup ≤  RR = 0.75 [0.62, 0.92]  P NI ≤  P sup =  *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

 Number at risk  Bivalirudin  Heparin + GPIIb/IIIa  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

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% definite1.4%2.2% probable0.5%0.3% acute (≤24 hrs)0.3%1.3% subacute (>24 hrs – 30d)1.7%1.2%0.30  *Protocol definition of stent thrombosis, CEC adjudicated

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 Bivalirudin Heparin + GP IIb/IIIa blocker

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

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

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) –0.61< Provisional in both arms ( HEAT, NAPLES 3 ) – Planned in both arms (ACUITY, TENACITY) – End pointHazard ratio95% CIp MACE – MI –1.23 < 0.05 Ischemia-driven revascularization –1.34 NS Mortality –1.18 Stent thrombosis – Major bleeding –0.78<  All Bivalirdudin vs Heparin STEMI trials: The Tradeoff Argument of  Bivalirudin versus Heparin Alone:  Benefit Stratified by GPI Use  2014  M. Sabatine et al, Lancet August 2014

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

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