Preoperative care/Catalogs/Beta-blocker evidence table

Trials in red, bold font have been discredited.

Selected^* randomized controlled trials of perioperative^† beta-blockers.
(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 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.
									0.6%	0.4%
POISE 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 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 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 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%	3%	0.4%	0%	Hypotension reported as an ADR:
									0.4%	0.2%
Neary 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 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 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.
									0%	0%
Mangano/ MSPI 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%	1%	Intraoperative inotropes given:
									13%	13%
* Trials were selected because they were included in the meta-analysis by Bangalore 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. † 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: Color indicates statistically significant differences with green indicating benefit and red indicating harm. BBSA noted more drug toxicity among patients with abnormal beta1-adrenergic receptor genetic polymorphisms. Mavs had trend toward most benefit in RCRI = 3.

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:

• 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.

• 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.

• 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.

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

• Raby KE, Brull SJ, Timimi F, Akhtar S, Rosenbaum S, Naimi C et al. (1999). "The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery.". Anesth Analg 88 (3): 477-82. PMID 10071990.

• 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.