Preoperative care/Catalogs/Beta-blocker evidence table

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Revision as of 10:58, 25 September 2009 by imported>Robert Badgett (Clarified that table includes all studies of > 100 patients and no longer selected for studies with at least one death.)
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Randomized controlled trials of perioperative beta-blockers* with at least 100 total patients.[1][2][3][4][5][6][7][8]
(See legend and notes at bottom on the table)
Patients Intervention Comparison Outcome Results
Mortality Stroke Beta-blocker toxicity
Rx Control Rx Control Rx Control

Decrease IV[1][9]
2009
Drug provided by Merck KGaA

1066 patients:
•estimated risk of perioperative cardiovascular death of ≥ 1%
• 0% vascular surgery
RCRI = 2: ~100%
Bisoprolol
• Started a median of 34 days preop
• Minimum allowed HR: >50 bpm
Open label Mortality at 30 days 1.9% 3.0% 0.8% 0.6% Heart failure, clinically significant bradycardia or hypotension:
0.6% 0.4%
POISE[2]
2008
Partially funded by AstraZeneca
8351 patients:
• 42% vascular surgery
RCRI = 2: uncertain
Metoprolol succinate
• Started day of surgery
• Minimum allowed HR: > 50 bpm
Placebo Mortality at two weeks Overall 1% 0.5% Clinically significant hypotension:
3.1% 2.3% 15% 9.7%
Vascular pts
Significant benefit on composite events. Mortality by surgery type not reported.
BBSA[3]
2007
Partially funded by industry.
224 patients:
• 1% vascular surgery
RCRI = 2: uncertain
Bisoprolol
• Started day of surgery
Minimum allowed HR: > 50bpm
Placebo Mortality at one year 0.9 0.9 1.8% 0% Hypotension:
0% 2.7%
DIPOM[4]
2006
Partially funded by AstraZeneca
921 patients:
• 7% vascular surgery
RCRI > 2: uncertain
• All had diabetes
Metoprolol succinate
• Started 0-1 days preop
• Minimum allowed HR: >55 bpm
Placebo Mortality at a median of 18 months 16% 16% 0.4% 0% Hypotension reported as an ADR:
0.4% 0.2%
MaVS[5]
2006
No industry funding.
496 patients:
• 100% vascular surgery
RCRI = 2: 40%
Metoprolol
• Start: day of surgery
• Minimum allowed HR: > 50 bpm while awake;
>45 bpm while asleep.
Placebo Hospital mortality 0% 1.6% 2.0% 1.6% Intraoperative hypotension treated:
46% 34%
POBBLE[6]
2005
No industry funding.
103 patients:
• 100% vascular surgery
RCRI > 2: uncertain
Metoprolol
• Start with test dose one day preop
• Minimum allowed HR: > 50 bpm
Placebo (anesthesiologists were not blinded) Mortality at 30 days 3% 1% 2% 0% Intraoperative inotropes given:
92% 64%
Decrease I[7]
1999
Uncertain funding.
112 patients:
• 100% vascular surgery
RCRI = 2: uncertain, at least 67%
• Abnl stress echo: 100%
Bisoprolol
• Started a median of 37 days preop
• Minimum allowed HR: > 50 bpm
Open label Mortality at 30 days 3.4%
(8.5%)
17.0% Not reported Discontinuation of study drug due to ADRs:
0% 0%
Mangano/ MSPI[8]
1996
No industry funding.
200 patients:
• 41% vascular surgery
RCRI > 2: uncertain
Atenolol
• Minimum allowed HR: > 55 bpm
Placebo Hospital mortality 4% 2% 4%[10] 1%[10] Intraoperative inotropes given:[10]
13% 13%

* This table does not include trials that used beta-blockers only for premedication[11][12][13] or only during postoperative care[14].
† Minimum allowed HR. The lowest heart rate allowed before beta-blockers were withheld.
‡ The DECREASE I trial was stopped early when a significant benefit was observed and the relative risk was 0.2. By Bayesian analysis, the relative risk is more likely to be 0.5 which leads to an event rate in the treatment group of 8.5%.
Notes:

  1. Color indicates statistically significant differences with green indicating benefit and red indicating harm.
  2. BBSA noted more drug toxicity among patients with abnormal beta1-adrenergic receptor genetic polymorphisms.[3]
  3. Mavs had trend toward most benefit in RCRI = 3.[5]

References

  1. 1.0 1.1 Dunkelgrun M, Boersma E, Schouten O, et al. (June 2009). "Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV)". Ann. Surg. 249 (6): 921–6. DOI:10.1097/SLA.0b013e3181a77d00. PMID 19474688. Research Blogging.
  2. 2.0 2.1 Devereaux PJ, Yang H, Yusuf S, et al. (May 2008). "Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial". Lancet 371 (9627): 1839–47. DOI:10.1016/S0140-6736(08)60601-7. PMID 18479744. Research Blogging.
  3. 3.0 3.1 3.2 Zaugg M, Bestmann L, Wacker J, et al. (July 2007). "Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up". Anesthesiology 107 (1): 33–44. DOI:10.1097/01.anes.0000267530.62344.a4. PMID 17585213. Research Blogging.
  4. 4.0 4.1 Juul AB, Wetterslev J, Gluud C, et al. (June 2006). "Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial". BMJ 332 (7556): 1482. DOI:10.1136/bmj.332.7556.1482. PMID 16793810. PMC 1482337. Research Blogging.
  5. 5.0 5.1 5.2 Yang H, Raymer K, Butler R, Parlow J, Roberts R (November 2006). "The effects of perioperative beta-blockade: results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial". Am. Heart J. 152 (5): 983–90. DOI:10.1016/j.ahj.2006.07.024. PMID 17070177. Research Blogging.
  6. 6.0 6.1 Brady AR, Gibbs JS, Greenhalgh RM, Powell JT, Sydes MR (April 2005). "Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: results of a randomized double-blind controlled trial". J. Vasc. Surg. 41 (4): 602–9. DOI:10.1016/j.jvs.2005.01.048. PMID 15874923. Research Blogging.
  7. 7.0 7.1 Poldermans D, Boersma E, Bax JJ, et al. (December 1999). "The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group". N. Engl. J. Med. 341 (24): 1789–94. PMID 10588963[e]
  8. 8.0 8.1 Mangano DT, Layug EL, Wallace A, Tateo I (December 1996). "Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group". N. Engl. J. Med. 335 (23): 1713–20. PMID 8929262[e]
  9. Schouten O et al. Fluvastatin and bisoprolol for the reduction of perioperative cardiac mortality and morbidity in high-risk patients undergoing non-cardiac surgery: rationale and design of the DECREASE-IV study. Am Heart J. 2004 Dec;148(6):1047-52. DOI:10.1016/j.ahj.2004.05.046 PMID 15632892
  10. 10.0 10.1 10.2 Wallace A, Layug B, Tateo I, et al. (January 1998). "Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group". Anesthesiology 88 (1): 7–17. PMID 9447850[e]
  11. Miller DR, Martineau RJ, Wynands JE, Hill J (1991). "Bolus administration of esmolol for controlling the haemodynamic response to tracheal intubation: the Canadian Multicentre Trial.". Can J Anaesth 38 (7): 849-58. PMID 1683818.
  12. Jakobsen CJ, Blom L, Brondbjerg M, Lenler-Petersen P (1990). "Effect of metoprolol and diazepam on pre-operative anxiety.". Anaesthesia 45 (1): 40-3. PMID 2316838.
  13. Stone JG, Foëx P, Sear JW, Johnson LL, Khambatta HJ, Triner L (1988). "Risk of myocardial ischaemia during anaesthesia in treated and untreated hypertensive patients.". Br J Anaesth 61 (6): 675-9. PMID 3207540.
  14. Urban MK, Markowitz SM, Gordon MA, Urquhart BL, Kligfield P (2000). "Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia.". Anesth Analg 90 (6): 1257-61. PMID 10825304.