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BLEEDING AND ACUTE CORONARY SYNDROMES

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This conference presentation by Dr. Syed Raza, a Cardiology Fellow at VCU Medical Center, focuses on the critical issue of bleeding in patients with acute coronary syndromes (ACS). It outlines the classification of bleeding scales, identifies associated risk factors, and discusses prognostic implications. The presentation emphasizes the need for consistent reporting of bleeding events using standardized scales (GUSTO, TIMI, ACUITY) and explores strategies to reduce bleeding risks in patients undergoing anti-thrombotic therapy and catheter-based interventions.

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BLEEDING AND ACUTE CORONARY SYNDROMES

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  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

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