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

Case report

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

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

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

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

Spontaneous subcutaneous hemorrhage

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

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

Relation between bleeding and mortality in ACS patients

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

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

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

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

30 day death according to bleeding (OASIS Registry, OASIS-2, CURE) John W. Eikelboom, et al.Circulation 2006;114: John W. Eikelboom, et al. Circulation 2006;114: fold  risk P< bleeding No bleeding 30 day death ( % ) (days) No. No bleeding bleeding N=34146

Increased mortality at Days 180 in patients with bleeding Rao et al. Am J Cardiol 2005;96: ,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 ( ) Moderate bleeding 9.9% (253/2566) 2.1 ( ) Severe bleeding 35.1% (107/305)7.5 ( ) Hazard Ratio GUSTO bleeding

The Risk Factors of Bleeding

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

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

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< J J Santopinto, et al. Heart 2003;89:

 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

 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

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

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

CRUSADE bleeding score PredictorScores Baseline Hct ， % < ≥400 CrCl: mL/min ≤1539 > > > > >1200 Heart rate ， bpm ≤ ≥12111 PredictorScores sex Male0 Female8 Signs of CHF on admission No0 Yes7 Prior vascular disease No0 Yes6 DM No0 Yes6 SBP on admission, mmHg ≤ ≥2015 Subherwal S,et al. Circulation. 2009;119: Hamorrhage riskCRUSADE scores High-low risk≤20 Low risk21-30 Moderate risk31-40 High risk41-50 Extremely high risk ≥50 Hct: CrCl: HR: 60 0 Sex: F 8 CHF: N 0 Prior history: Y 6 DM: N 0 SBP: Score: 59

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

Thanks ！ Thanks ！