BLEEDING AND ACUTE CORONARY SYNDROMES

1. BLEEDING AND ACUTE CORONARY SYNDROMES Cardiac Catherization Conference Syed Raza MD Cardiology Fellow VCU Medical Center 06/02/2011

2. Outline: • Introduction- Classification of bleeding scales • Risk factors • Prognostic implications • Strategies to reduce bleeding • Conclusion

3. Bleeding and ACS • In patients with acute coronary syndromes, early treatment with anti-thrombotic medications and catheter based interventions reduced ischemic events but at an increased risk of bleeding. • The reported incidence of bleeding after treatment for ACS ranges from 1% to 10% and depends on a number of factors. • Bleeding is strongly associated with adverse outcomes in patients with ACS. 2/3rd of patients bleed at access site. • Bleeding has been classified by different investigators using different scales.

4. Bleeding Scales- Why? • Bleeding scale = Common language • Consistent reporting of bleeding events across different populations, regions and trials. • Facilitate comparisons across different regions and populations, treatment strategies and different data sets.

5. Popular Bleeding Scales • GUSTO • TIMI • ACUITY • REPLACE-2

6. GUSTO Severe or life-threatening: Intracranial or bleeding that causes hemodynamic compromise and requires intervention. Moderate: Bleeding that requires blood transfusion but does not result in hemodynamic compromise. Mild: Bleeding that does not meet criteria for either severe or moderate bleeding.

7. TIMI Major: • Intracranial or ≥ 5 g/dl decrease in the hemoglobin concentration or ≥ 15% decrease in HCT. Minor: • Observed blood loss with ≥ 3 g/dl decrease in the Hgb concentration or ≥ 10% decrease in HCT Minimal: • All other bleeding

8. ACUITY Major: • Intracranial or intraocular bleeding • Access site bleeding requiring intervention • Hematoma ≥ 5 cm in diameter • Drop in Hgb ≥ 4 g/dl without overt source of bleeding or ≥ 3 g/dl with an overt source • Bleeding requiring reoperation or transfusion Minor: • All other bleeding

9. Case 1 • 70 y o F with CAD s/p PCI with DES to LAD 6 months ago • On aspirin 81 mg po daily and plavix 75 mg po daily • Fell and brought to ED • Head CT shows a 2 x 3 cm frontal intraparenchymal hemorrhage • How do you classify her bleeding? • GUSTO = Major • TIMI = Major • ACUITY = Major

10. Case 2 • 58 y o male with NSTEMI received DES to LAD • On ASA 325 mg po daily and plavix 75 mg po daily • Bivalirudin given during PCI • Had hemetemesis with Hgb drop from 13 g/dl to 10.5 g/dl (2.5 g/dl drop). Vitals remained stable. • Received 1 unit of PRBCs • EGD- non-bleeding ulcer= PPI Rx • How do you classify his bleeding? • GUSTO = Moderate • TIMI = Minimal • ACUITY = Major

11. Bleeding Classifications • Clinical elements • Laboratory values • Response to bleeding • Optimal scale should probably have all the above elements

12. Risk Factors Associated with Bleeding • Older age • Female sex • Renal failure • History of bleeding • Use of GP IIb/IIIa use

13. Risk Factors For Bleeding- Evidence • GRACE • ACUITY • CRUSADE

14. Risk Factors For Bleeding

15. GRACE • 24000 patients with ACS were studied. • Risk factors for bleeding were identified using logistic regression analysis. • Major bleeding was defined as life-threatening bleeding requiring transfusion of ≥ 2 units of PRBCs, or HCT decrease of 10% or hemorrhagic/subdural hematoma. • Major bleeding occurred in 3.9% overall patients and: • 4.8 % with STEMI • 4.7% with NSTEMI • 2.3% with unstable angina

16. GRACE

17. Bleeding = Mortality GRACE Registry Data

18. ACUITY

19. ACUITY • > 13000 patients with ACS were randomized to: • Heparin plus GPI • Bivalirudin plus GPI • Bivalirudin alone • 3 primary outcomes (30 days): • Composite ischemia • Major bleeding • Net clinical outcome

20. ACUITY Independent Predictors of Major Bleeding

21. ACUITY

22. ACUITY Independent predictors of mortality

23. ACUITY

24. CRUSADE (Circulation. 2009;119:1873-1882.)

25. CRUSADE • > 89000 patients with NSTEMI were studied. • Developed and validated a model that identified 8 independent predictors of in-hospital mortality. • Bleeding score (1-100) was created by assigning weighted integers that corresponded to the coefficient of each variable. • Rate of major bleeding increased by bleeding risk quintiles. Circulation. 2009;119:1873-1882

26. CRUSADE

27. CRUSADE • Very low 20 or less • Low 21-30 • Moderate 31-40 • High 41-50 • Very high > 50

28. CRUSADE

29. CRUSADE

30. CRUSADE

31. Euro Heart Survey-ACS Data (STEMI) Gitt et al. JACC 2010;55;A101.E945

32. Euro Heart Survey-ACS Data (NSTEMI) Gitt et al. JACC 2010;55;A115.E1073

33. Bleeding Mortality BLEEDING = MORTALITY BLEEDING = HIGH RISK PATIENTS = MORTALITY

34. BLEEDING=MORTALITY Eikelboom et al Circulation. 2006;114:774-782

35. Pooled analysis of > 34000 patients from OASIS, OASIS-2 and CURE trial. • Major bleeding defined as that requiring > 2 units of PRBCs or life-threatening >intracranial, Hgb drop of atleast 5 g/dl, requiring surgical intervention. All other was minor. • Primary outcome was death during the first 30 days. • Also examined were the association between bleeding and outcomes in subgroups and dose relation between bleeding and death.

36. 30 day mortality Eikelboom et al Circulation. 2006;114:774-782

37. 6 month mortality Eikelboom et al Circulation. 2006;114:774-782

38. Dose relation Eikelboom et al Circulation. 2006;114:774-782

39. Conclusions: • Increase in mortality among patients who develop major bleeding remains evident after adjustment for baseline characteristics. • Mortality is greatest in first 30 days and is markedly reduced if patients survive at least 30 days after a major bleed. • There appears to be a strong, consistent, temporal and dose related association between major bleeding and death. Eikelboom et al Circulation. 2006;114:774-782

40. If bleeding kills….. Can blood transfusion save lives?

41. Transfusion > Mortality • 24000 pts with ACS analyzed from GUSTO IIb, PURSUIT and PRAGON. • 10% underwent transfusion. • Transfusion was associated with HR of 3.94 [CI 3.26-4.75] for death. • Predicted probability of 30 day death was higher with transfusion at nadir HCT > 25%. Rao et al. JAMA. 2004;292:1555-1562

42. Transfusion > Mortality Doyle et al J Am Coll Cardiol 2009;53:2019–27

43. Older blood > higher mortality • Red cell transfusion in post-CABG and valve pts was studied. • 3000 pts were given old blood (> 2 weeks) and 3000 pts were given new blood (< 2 weeks). • At 1 year, mortality was significantly less in pts given new blood (7.4% vs 11%, p < 0.001). Koch et al. N Engl J Med 2008;358:1229-39.

44. Possible mechanisms linking bleeding with increased mortality

45. Strategies to reduce bleeding • Assess bleeding risk • Lower risk drugs • Use of radial site for catherization

46. ` • About 17000 patients in ACUITY and HORIZON-AMI trial were studied • Independent predictors of non-CABG related bleeding within 30 days were evaluated • Integer risk score for major bleeding within 30 days was developed

47. Predictors of major bleeding

48. Integer risk score

49. Integer risk score • < 10 = Low risk • 10-14= Moderate • 15-19= High • 20 or more= Very high

50. CRUSADE BLEEDING SCOREwww.crusadebleedingscore.org • Very low 20 or less • Low 21-30 • Moderate 31-40 • High 41-50 • Very high > 50