The risk of iatrogenic bleeding in acute coronary syndromes and long-term mortality

Current Opinion in Cardiology

Volumn 23, Issue 4, 2008, Pages 327-334

  Sobieraj Teague, Magdalena ^a   Gallus, Alexander S ^a   Eikelboom, John W ^b  

^a FLINDERS MEDICAL CENTRE   (Australia)

^b MCMASTER UNIVERSITY   (Canada)

Author keywords

Acute coronary syndrome; Bleeding; Prognosis

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; CLOPIDOGREL; ENOXAPARIN; ESOMEPRAZOLE; FONDAPARINUX; HEPARIN; HIRULOG; PLACEBO; PROTON PUMP INHIBITOR;

ACUTE CORONARY SYNDROME; ANEMIA; BLEEDING; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DISEASE ASSOCIATION; HUMAN; HYPOVOLEMIA; IATROGENIC DISEASE; KIDNEY DYSPLASIA; MONOTHERAPY; MORBIDITY; MORTALITY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SEX DIFFERENCE; STOMACH HEMORRHAGE; TRANSFUSION;

ACUTE CORONARY SYNDROME; FIBRINOLYTIC AGENTS; HEMORRHAGE; HUMANS; IATROGENIC DISEASE; INCIDENCE; RISK FACTORS; TIME FACTORS; TREATMENT OUTCOME;

EID: 44649174415     PISSN: 02684705     EISSN: None     Source Type: Journal    
DOI: 10.1097/HCO.0b013e3283021c5b     Document Type: Review

References (49)

1. Avezum A, Makdisse M, Spencer F, et al. Impact of age on management and outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2005; 149:67-73.
2. Eikelboom JW, Mehta SR, Anand SS, et al. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006; 114:774-782.
3. Rao SV, O'Grady K, Pieper KS, et al. Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol 2005; 96:1200-1206.
4. Kinnaird TD, Stabile E, Mintz GS, et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. Am J Cardiol 2003; 92:930-935.
5. Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol 2007; 49:1362-1368. This large study identified major bleeding as a powerful independent predictor of 30-day mortality and reported independent risk factors for major bleeding.
6. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345:494-502.
7. Alexander KP, Chen AY, Roe MT, et al. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. JAMA 2005; 294:3108-3116.
8. Moscucci M, Fox KA, Cannon CP, et al. Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2003; 24:1815-1823.
9. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med 1993; 329:673-682.
10. Mehta SR, Yusuf S, Granger CB, et al. Design and rationale of the MICHELANGELO Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS)-5 trial program evaluating fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST-segment elevation acute coronary syndromes. Am Heart J 2005; 150:1107.
11. Global Organization Network (PARAGON)-B Investigators. Randomized placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes. Circulation 2002; 105:316-321.
12. Montalescot G, White HD, Gallo R, et al. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006; 355:1006-1017.
13. Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987; 76:142-154.
14. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in nonsurgical patients. J Thromb Haemost 2005; 3:692-694.
15. Rao SV, O'Grady K, Pieper KS, et al. A comparison of the clinical impact of bleeding measured by two different classifications among patients with acute coronary syndromes. J Am Coll Cardiol 2006; 47:809-816.
16. Serebruany VL, Atar D. Assessment of bleeding events in clinical trials - proposal of a new classification. Am J Cardiol 2007; 99:288-290.
17. Steinhubl SR, Kastrati A, Berger PB. Variation in the definitions of bleeding in clinical trials of patients with acute coronary syndromes and undergoing percutaneous coronary interventions and its impact on the apparent safety of antithrombotic drugs. Am Heart J 2007; 154:3-11. This review compared the various criteria used to characterize major bleeding in recent studies of antithrombotic therapies in ACS and demonstrated that different definitions can lead to different conclusions about the safety of an antithrombotic regimen.
18. Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004; 292:45-54.
19. Fox KA, Mehta SR, Peters R, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation 2004; 110:1202-1208.
20. Yusuf S, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006; 354:1464-1476.
21. Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289:853-863.
22. Lauer MA, Karweit JA, Cascade EF, et al. Practice patterns and outcomes of percutaneous coronary interventions in the United States: 1995 to 1997. Am J Cardiol 2002; 89:924-929.
23. Rao SV, Chiswell K, Sun JL, et al. International variation in the use of blood transfusion in patients with non-ST-segment elevation acute coronary syndromes. Am J Cardiol 2008; 101:25-29. This large analysis of pooled data from three RCTs examined international patterns of blood transfusion in patients with NSTEMI and demonstrated higher transfusion rates in US patients than non-US patients. This was true for patients undergoing invasive procedures as well as those managed noninvasively. The risk of transfusion persisted after adjustment for other risk factors.
24. Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Lancet 1999; 353:429-438.
25. Lenderink T, Boersma E, Ruzyllo W, et al. Bleeding events with abciximab in acute coronary syndromes without early revascularization: an analysis of GUSTO IV-ACS. Am Heart J 2004; 147:865-873.
26. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355:2203-2216.
27. Van de Werf F, Barron HV, Armstrong PW, et al. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA. Eur Heart J 2001; 22:2253-2261.
28. Fox KA, Bassand JP, Mehta SR, et al. Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes. Ann Intern Med 2007; 147:304-310. This subgroup analysis of the OASIS-5 trial examined the efficacy and safety of fondaparinux and enoxaparin in patients with renal impairment. Overall major bleeding rate was lower for fondaparinux than enoxaparin. The greatest benefit was observed in patients with renal dysfunction.
29. Stone GW, White HD, Ohman EM, et al. Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet 2007; 369:907-919. This trial in moderate and high-risk ACS patients undergoing PCI demonstrated reduced bleeding rates for patients treated with bivalirudin alone as compared with those treated with heparin plus GPI. Ischaemic outcomes were comparable for both treatment groups.
30. Brieger D, Van de Werf F, Avezum A, et al. Interactions between heparins, glycoprotein IIb/IIIa antagonists, and coronary intervention. The Global Registry of Acute Coronary Events (GRACE). Am Heart J 2007; 153:960-969. This is a report from GRACE registry (international observational study), which reported very high major bleeding rates in elderly patients treated with GPI and heparin.
31. Alexander KP, Chen AY, Newby LK, et al. Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) initiative. Circulation 2006; 114:1380-1387.
32. Spencer FA, Moscucci M, Granger CB, et al. Does comorbidity account for the excess mortality in patients with major bleeding in acute myocardial infarction? Circulation 2007; 116:2793-2801. One of the largest studies to date reporting increased 30-day mortality rate in patients with ACS complicated by major bleeding. Although patients with major bleeding were older and sicker, the association with increased early mortality persisted after adjustment for confounders.
33. Manoukian SV, Voeltz MD, Eikelboom J. Bleeding complications in acute coronary syndromes and percutaneous coronary intervention: predictors, prognostic significance, and paradigms for reducing risk. Clin Cardiol 2007; 30:II24-II34. Comprehensive review exploring the association between bleeding and adverse outcomes in ACS patients.
34. Nelson MA, Voeltz MD, Feit F, et al. Elderly patients with major bleeding or need for transfusion complicating percutaneous coronary intervention have an increased risk of 30-day and 1-year mortality. Circulation 2006; 114:II687.
35. Ndrepepa G, Berger PB, Mehilli J, et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple endpoint. J Am Coll Cardiol 2008; 51:690-697.
36. Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993; 269:3024-3029.
37. Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999; 340:409-417.
38. Murphy GJ, Reeves BC, Rogers CA, et al. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 2007; 116:2544-2552. This large, single-centre, observational retrospective study reported transfusion outcomes in cardiac surgery patients. Transfusion was strongly associated with increased early and late mortality, with infection, with composite ischaemic outcome (stroke, MI, and renal failure), and with increased overall hospitalization costs.
39. Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004; 292:1555-1562.
40. Yang X, Alexander KP, Chen AY, et al. The implications of blood transfusions for patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE National Quality Improvement Initiative. J Am Coll Cardiol 2005; 46:1490-1495.
41. Perrotta PL, Snyder EL. Noninfectious complications of transfusion therapy. Blood Rev 2001; 15:69-83.
42. Basran S, Frumento RJ, Cohen A, et al. The association between duration of storage of transfused red blood cells and morbidity and mortality after reoperative cardiac surgery. Anesth Analg 2006; 103: 15-20 (table of contents).
43. Wallis JP. Nitric oxide and blood: a review. Transfus Med 2005; 15:1-11.
44. Lincoff AM, Kleiman NS, Kereiakes DJ, et al. Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA 2004; 292:696-703.
45. Cantor WJ, Mahaffey KW, Huang Z, et al. Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal. Catheter Cardiovasc Interv 2007; 69:73-83.
46. Louvard Y, Benamer H, Garot P, et al. Comparison of transradial and transfemoral approaches for coronary angiography and angioplasty in octogenarians (the OCTOPLUS study). Am J Cardiol 2004; 94:1177-1180.
47. Koreny M, Riedmuller E, Nikfardjam M, et al. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis. JAMA 2004; 291:350-357.
48. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005; 352:238-244.
49. Ng FH, Wong SY, Lam KF, et al. Gastrointestinal bleeding in patients receiving a combination of aspirin, clopidogrel, and enoxaparin in acute coronary syndrome. Am J Gastroenterol 2008; 103:865-871.