Preoperative care/Catalogs/Beta-blocker evidence table

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Trials in red, bold font have been discredited.[1]

Selected* randomized controlled trials of perioperative beta-blockers.[2][3][4][5][6][7][8][9][10][11]
(See legend and notes at bottom on the table)
Patients Intervention Comparison Outcome Results Comment
Mortality Stroke Beta-blocker toxicity
Rx Control Rx Control Rx Control

Decrease IV[2][12]
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: • Investigator has been accused of fraud.[13]
0.6% 0.4%
POISE[3]
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[4]
2007
Partially funded by industry.
224 patients:
• 1% vascular surgery
RCRI = 2: uncertain
Bisoprolol
• Started day of surgery
Minimum allowed HR: > 50bpm
Placebo Hospital mortality 0.9% 0.9% 1.8% 0% Hypotension:
0% 2.7%
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 0.4% 2.8% 2.0% 1.6% Intraoperative hypotension treated:
46% 34%
DIPOM[6]
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 Hospital mortality 4%[11] 3%[11] 0.4% 0% Hypotension reported as an ADR:
0.4% 0.2%
Neary[7]
2006
No industry funding.
38 patients:
• 21% vascular surgery
RCRI > 2: uncertain
Atenolol
• Started at induction with maximum dose 5 mg IV
• Minimum allowed HR: uncertain
• Maximum daily dose: 100 mg
Placebo Hospital mortality 17% 25% Not reported Hypotension reported as an ADR:
5.5%
(one pt)
5.0%
(one pt)
POBBLE[8]
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[9]
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: • Study was stopped early; effect likely exaggerated.
• Investigator has been accused of fraud.[13]
0% 0%
Mangano/ MSPI[10]
1996
No industry funding.
200 patients:
• 41% vascular surgery
RCRI > 2: uncertain
Atenolol
• Started IV on the day of surgery with maximum dose 10 mg IV
• Minimum allowed HR: > 55 bpm
• Maximum daily dose: 100 mg
Placebo Hospital mortality 4% 2% 4%[14] 1%[14] Intraoperative inotropes given:[14]
13% 13%

* Trials were selected because they were included in the meta-analysis by Bangalore[11] if the trial studied patients who had existing cardiac disease, risk factors for cardiac disease, or were undergoing vascular surgery. Additional excluded trials and their reasons for exclusion are listed below.
Qualifying trials published after the meta-analysis by Bangalore have been added.[2] † This table does not include trials that used beta-blockers only for premedication or only during postoperative care.
‡ 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.[4]
  3. Mavs had trend toward most benefit in RCRI = 3.[5]

Excluded trials

The following randomized controlled trials of beta-blockers were excluded because beta-blockers were only given as premedication or only give during postoperative care. Trials that only used beta-blockers only for premedication:

Trials that only used beta-blockers only during postoperative care:


References

  1. Cole, G. D.; D. P. Francis (2014-08-29). "Perioperative blockade: guidelines do not reflect the problems with the evidence from the DECREASE trials". BMJ 349 (aug29 8): –5210-g5210. DOI:10.1136/bmj.g5210. ISSN 1756-1833. Retrieved on 2014-09-03. Research Blogging.
  2. 2.0 2.1 2.2 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.
  3. 3.0 3.1 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.
  4. 4.0 4.1 4.2 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.
  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 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.
  7. 7.0 7.1 Neary WD, McCrirrick A, Foy C, Heather BP, Earnshaw JJ (2006). "Lessons learned from a randomised controlled study of perioperative beta blockade in high risk patients undergoing emergency surgery.". Surgeon 4 (3): 139-43. PMID 16764198.
  8. 8.0 8.1 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.
  9. 9.0 9.1 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]
  10. 10.0 10.1 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]
  11. 11.0 11.1 11.2 11.3 Bangalore S, Wetterslev J, Pranesh S, Sawhney S, Gluud C, Messerli FH (2008). "Perioperative beta blockers in patients having non-cardiac surgery: a meta-analysis.". Lancet 372 (9654): 1962-76. DOI:10.1016/S0140-6736(08)61560-3. PMID 19012955. Research Blogging. Review in: Ann Intern Med. 2009 Mar 17;150(6):JC3-4
  12. 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
  13. 13.0 13.1 Chopra V, Eagle KA (2012). "Perioperative mischief: the price of academic misconduct.". Am J Med 125 (10): 953-5. DOI:10.1016/j.amjmed.2012.03.014. PMID 22884175. Research Blogging.
  14. 14.0 14.1 14.2 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]