1. Anticoagulation Management in ACS Patient with Bleeding Risk Shanghai No.6th People’s Hospital Department of Cardiology Lu Zhigang

2. Case report

3. At admission  ***, female, 86-years-old, WT 60kg 。  Admitted to hospital on Jun 9 th 2010 because of persistent chest pain for 2 hours.  Prior history Hypertension OMI twice  Cigarette smoking

4. At admission  BP 129/81mmHg at admission  EKG ： atrial fibrillation, ST segment depressed in I 、 II 、 V3-6  Cardiac enzyme: cTnI 1.61ug/L, CKMB 7.9ug/L  Blood routine: Hb 100g/L,Hct 28.3%, plt 108*10^9/L  renal function: Scr 116umol/L  Diagnosis: ACS

7. Treatment  Aspirin 0.1 qd po  Clopidogrel 75mg qd po  Nadroparin 4100u iH q12hr until Jun 17  NS 250mL+ Salvianolate 0.2 / ivgtt qd  Refused to coronary intervention

8. Course in hospital  Before draw on Jun 17 th complaint of tenderness in the right chest  On Jun 17 th morning a Φ6cm mass was palpated in the right lateral breast, which was hard, tenderness and no flare  On the afternoon of Jun 17 th ecchymosis was seen in the right lateral breast and right armpit with tenderness and no fluctuation soft tissues in the right chest was swelling  On Jun 18 th morning hematoma was seen in the same area

9. Spontaneous subcutaneous hemorrhage

10. Changes of blood routine TimeHb (g/L)Hct (%)WBC (*10^9/L) Plt (*10^9/L) Jun 9 th 10028.35.6108 Jun 17 th 9:008925.63.9124 Jun 17 th 20:307522.46.3131 Jun 18 th 6:0063187.8136 Jun 21 st 9:005515.76.3153

11. Risk  bleeding Benefit  Thrombosis Net profits ?? of anticoagulation ??

12. Relation between bleeding and mortality in ACS patients

13. Changes in recent 20 years about ACS anticoagulation 16-20% 12-15% 8-12% 6-10% 4-8% Death / MI 1988 ASA 1992 ASA+ Heparin 1998 ASA+ Heparin+ Anti- GPIIB/IIIA 2003 ASA+ LMWH + Clopidogrel + Intervention With permission from Christopher Cannon < 1988 bleeding

14. Bleeding classification of ESC guidelines TIMI bleeding major major Intracranial haemorrhage or clinically overt bleeding (including image) >= 5 g/dL decrease in the haemoglobin concentration minor minor Clinically overt bleeding (including image) with 3 to < 5 g/dL decrease in the haemoglobin concentration minimal minimal clinically overt bleeding (including image) with a < 3 g/dL decrease in the haemoglobin concentration GUSTO bleeding ESC Guidelines for the Mangement of NSTE-ACS Severe or life threatening Severe or life threatening Either intracranial haemorrhage or bleeding that causes haemodynamic compromise and requires intervention Moderate Moderate Bleeding that requires blood transfusion but does not results haemodynamic compromise Mild Mild Bleeding that does not meet criteria for either severe or moderate bleeding

15. Major bleeding rates in studys Patients percentage Rao SV, et al. European Heart Journal 2007;28:1193-1204

16. GRACE ： major bleeding increased death rates in ACS patients et al. Moscucci M et, et al. Eur Heart J 2003;24:1815-1823 In-hospital death (%) **** **** **p<0.001 overallUA NSTEMISTEMI

17. 30 day death according to bleeding (OASIS Registry, OASIS-2, CURE) John W. Eikelboom, et al.Circulation 2006;114: 774 - 782 John W. Eikelboom, et al. Circulation 2006;114: 774 - 782 5 fold  risk P<0.0001 bleeding No bleeding 30 day death ( % ) 33676 3341933157 3299032879 32769 32710 470 459440 430 420410408 (days) No. No bleeding bleeding N=34146

18. Increased mortality at Days 180 in patients with bleeding Rao et al. Am J Cardiol 2005;96:1200-1206 26,452 ACS patients from GUSTO IIb, PURSUIT and PARAGON A&B study mortality adjusted HR (95% CI) No bleeding 5.2% (983/18,886)1.0 Minor bleeding 6.3% (273/4358)1.4 (1.2-1.6) Moderate bleeding 9.9% (253/2566) 2.1 (1.8-2.4) Severe bleeding 35.1% (107/305)7.5 (6.1-9.3) Hazard Ratio GUSTO bleeding -5151510

19. The Risk Factors of Bleeding

20. Multivariate model for bleeding in patients with ACS Multivariate model for bleeding in patients with ACS

21. variable Adjusted OR P value Age (per 10y increase) 1.28<0.0001 Female sex 1.43<0.0001 History of renal insufficiency 1.480.0004 History of bleeding 2.83<0.0001 GP IIb/IIIa blockers 1.93<0.0001 PCI1.63<0.0001 Moscucci M, et al. Eur Heart J 2003;24:1815-23

22. Death MI MI stroke Major bleeding * * * Patient percentage GRACE (n=11774) ： GRACE (n=11774) ： bleeding rates and mortality increased in ACS patients bleeding rates and mortality increased in ACS patients with renal insufficient with renal insufficient *p<0.05, **p<0.0001 J J Santopinto, et al. Heart 2003;89:1003-1008

23.  CrCl and/or GFR should be calculated for every patient hospitalised for NSTE-ACS (I-B) 。 Elderly people, women and low body weight patients merit special attention as near normal serum creatinine level maybe associated with lower than expected CrCl and GFR level (I-B).  In patients with CrCl<30 ml/min or GFR <30 ml/min/1.73m², a careful approach to the use of anticoagulants is recommended (I-C) … … … … Recommendations for patients with CKD ESC Guidelines for the Mangement of NSTE-ACS

24.  Assessment of bleeding risk is an important component of the decision making process…(I-B) Recommendations for bleeding complications ESC Guidelines for the Mangement of NSTE-ACS

25. Risk factors of ischemic events  ACS recently happened  PCI recently performed  reoccurred ACS after stopping OAT  LVEF<30%  Diabetes  Multi coronary disease  Stent length >25mm  Vessels diameter <2.5mm evascularization  Incomplete revascularization  Arterial sclerosis lesions >2 Risk factors of hemorrhage events  Past history of hemorrhage  Recurrent hemorrhagic ulcer  Intracranial operation  Transurethral prostatectomy  Extensive dissociated operation Essential risk factors  Elders  Female  Fat  Heart failure  Renal insufficient  Comorbidities Anticoagulation

26. In our case  Ccr = [(140-age) * weight (kg)] / [0.818×Scr (umol/L)] *0.85 (female) = [(140-86) * 60 (kg)] / [0.818×116 (umol/L)] *0.85 (female) = 29.1mL/min

27. CRUSADE bleeding score PredictorScores Baseline Hct ， % <319 31-33.97 34-36.93 37-39.92 ≥400 CrCl: mL/min ≤1539 >15-3035 >30-6028 >60-9017 >90-1207 >1200 Heart rate ， bpm ≤700 71-801 81-903 91-1006 101-1108 111-12010 ≥12111 PredictorScores sex Male0 Female8 Signs of CHF on admission No0 Yes7 Prior vascular disease No0 Yes6 DM No0 Yes6 SBP on admission, mmHg ≤9010 91-1008 101-1205 121-1801 181-2003 ≥2015 Subherwal S,et al. Circulation. 2009;119:1873-82 Hamorrhage riskCRUSADE scores High-low risk≤20 Low risk21-30 Moderate risk31-40 High risk41-50 Extremely high risk ≥50 Hct: 28.3 9 CrCl: 29.1 35 HR: 60 0 Sex: F 8 CHF: N 0 Prior history: Y 6 DM: N 0 SBP: 129 1 Score: 59

28. Summary  Prevention of bleeding events is equally as important as prevention of ischemic events  Risk of bleeding is associated with age, sex, weight and CrCl etc  Bleeding carries a high risk of death, MI and stroke  Risk stratification for bleeding should be part of the decision making process

29. Thanks ！ Thanks ！