Review of the evidence that supported the use of Beta-blockers in the peri-operative setting and the data from the POISE trial.

1. Perioperative Beta-blockers in non-cardiac surgery and the POISE trial: evidence revisited Moises Auron MD FAAP Hospital Medicine Cleveland Clinic

10. Evidence supporting BB use

12. Mangano, et al. NEJM 1996 Atenolol 10 3 0 0.019 21 24 mo 0.005 14 12 mo < 0.001 8 6 mo P Placebo All cause death (%)

17. Wallace, A, et al. Anesthesiology. 1998; 88: 7-17.

18. Evidence supporting BB use: DECREASE trial NEJM. 1999; 341(24): 1789-1794

21. Poldermans, et al. NEJM.1999 P Placebo Bisoprolol < 0.001 34% 3.4% End-point < 0.001 9 (17%) 0 Non-fatal MI 0.002 9 (17%) 2 (3.4%) Cardiac causes

24. Boersma, et al. JAMA 2001

28. Feringa HHH, et al. Circulation . 2006;114[suppl I]:I-344 –I-349.

32. The start of disbelief BMJ. 2005; 331: 313-321.

35. Devereaux, et al. BMJ 2005. The Lan-DeMets sequential monitoring boundary, assumes a 10% control event rate and a 25% RR reduction with 80% power and a two sided = 0.01. Cumulative meta-analysis assessing the effect of POBB on 30 day risk of major perioperative CV events in patients having non-cardiac surgery. Cumulative evidence is inconclusive

36. Current recommendations Circulation. 1999; 100: 1043 – 1049.

37. N Engl J Med 2005;353: 349-61.

39. Lindenauer, NEJM 2005.

41. Yang H, et al. Am Heart J. 2006; 152: 983 – 90.

44. Powell JT, et al. J Vasc Surg 2005;41:602-9.)

46. POBBLE Trial Time from surgery to discharge Placebo - median of 12 days (95% confidence interval, 9-19 days) Metoprolol – median of 10 days (95% confidence interval, 8-12 days) group (adjusted HR 1.71; 95% CI 1.09-2.66; P < .02 ). Powell JT, et al. J Vasc Surg 2005;41:602-9.)

48. DIPOM (Diabetes Postoperative Mortality and Morbidity) Trial BMJ. 332 (7556):1482-88

51. Current recommendations Circulation 2007;116;e418-e499

52. 2007 AHA/ACC Perioperative guidelines

53. 2007 AHA/ACC Perioperative guidelines

55. Finally… Devereaux PJ, et al. Lancet 2008; 371: 1839 – 47. PeriOperative ISchemic Evaluation

60. POISE

66. POISE

70. Results

71. Results

72. Results

73. Results

74. Results Primary outcome MI

75. Results

76. Results Death Stroke

78. Results HR1.94 (CI 1.01-3.69; P = 0.0450)

79. Results

81. Results

83. RR 1.29, 95% CI 1.02–1.62; P = 0.03

84. Discussion RR 1.29, 95% CI 1.02–1.62; P = 0.03