Dissections INTERVENTIONAL

3 April 2009
Evidence-based Medicine for Surgeons

Peripheral vascular surgery using targeted beta blockade reduces perioperative cardiac event
rate
Authors: de Virgilio C, Yaghoubian A, Nguyen A et al
Journal: J Am Coll Surg 2009; 208:14-20
Centre: Harbor-UCLA Medical Center, Torrance CA, USA
Preoperative cardiac clearance often includes stress testing in many protocols. There is doubt
regarding the value of dipyridamole-thalllium stress testing (the most commonly used test) as a
BACKGROUND predictor of adverse perioperative cardiac events. The question arises whether there is a subset
of patients who can receive perioperative beta blockade and proceed directly to surgery without
any stress testing.
Authors' claim(s): “...peripheral vascular surgery and lower extremity
RESEARCH QUESTION amputation can be safely performed without preoperative cardiac testing in low
to intermediate cardiac risk patients, provided universal perioperative [beta]
Population blockade is administered.”
Patients undergoing vascular
surgery or lower limb amputation IN SUMMARY
with low to intermediate cardiac
risk. Beta blockade and adverse perioperative cardiac events
Study (n=100) Controls (n=80)
Indicator variable
Universal "targeted" beta blockage Number received beta blockade 100 49
and subsequent surgery without Arrhythmia 0 2
any stress testing
Myocardial infarction 2 7
Outcome variable
CHF 0 1
Cardiac events occurring within 30
Cardiopulmonary arrest 0 1
days of the surgery or in the same
hospitalization. Cardiac death 0 0

Comparison Composite endpoint 2 8

Although the authors submit some fancy statistical analysis that is seriously
A matched group of controls,
questionable, the numbers are simple enough for you to be the judge. Keep
selected from a retrospective
in mind the worrisome fact that 49 of 80 controls received beta blockade, a
cohort of patients from 2001-03.
statistic that is snuck in amidst the fine print.

THE BOTTOM LINE

This paper, best described as being one of a "me too, me three ..." genre, reinvents the wheel in an unconvincing manner.
From an EBM standpoint, flaws abound. To begin with, the target heart rate was inadequately established in a large
number. The controls are a mixed bag of case-controls which the authors have clubbed together for comparison. While
asserting that there is no need for stress testing, only 11 of 80 patients in the control group had a stress test and 49
received beta blockade! The authors are comparing apples with a mixed bag of apples and oranges. And, the real zinger
is the statement found tucked in the "Composite study end points" section that states: " Among the 24 control patients
who did not receive beta blockade, there were 2 cardiac events. Among the 48 patients who did receive beta blockade,
there were 6 cardiac events." You don't even need a calculator, leave alone a biostatistician, to see the contradictory, jaw-
dropping inference.

EBM-O-METER
Evidence level Overall rating Bias levels
Double blind RCT Sampling
Randomized controlled trial (RCT) Comparison
Trash Swiss Safe News-
Prospective cohort study - not randomized cheese worthy Measurement
Life's too Holds water
short for this Full of holes “Just do it”
Case controlled study
Interestingl | Novel l | Feasible l
Case series - retrospective  Ethical l | Resource saving l

The devil is in the details (more on the paper) ... 

© Dr Arjun Rajagopalan
 SAMPLING
Sample type Inclusion criteria Exclusion criteria Final score card
Simple random All patients undergoing MI within 6 mths  Study Controls
major lower extremity NYHA Class III/IV 
Stratified random Target ? ?
revascularization, Urgent procedures 
Cluster carotid Aortic surgery ? Accessible ? ?
endarterectomy, or Minor amputation 
Consecutive major lower extremity Trauma  Intended 100 100
Convenience amputation  Drop outs 0 20
Judgmental Study 100 80

 = Reasonable | ? = Arguable |  = Questionable

Sampling bias: An a priori sample size estimation based on anticipated differences between groups was not done.
There is no mention of the number of accessible patients who were excluded from the study after applying the
selection criteria The sample is limited to patients with vascular disease that does not involve the aorta.

COMPARISON
Randomized Case-control Non-random Historical None

Controls - details
Allocation details Metaprolol was administered preoperatively in all study patients, in an incremental fashion to
achieve a target heart rate of 50 - 60 beats/ minute (achieved only in 24% of patients) before
surgery. The comparison group was obtained from patients seen between 2001 and 2003 who
were matched by age and operative procedure. Only 80 controls were obtained
Comparability The two groups were similar in demographic characteristics and co-morbidties.
Disparity 49 (61%) patients in the control group had received beta blockade. No patient in the study
group had a stress test; 11 of 80 in the controls underwent stress testing.

Comparison bias: The cardinal principle in designing a case-control study is that the controls and the study samples
be identical in all aspects except the indicator variable that is under study: in this case the use of beta blockade
without stress testing. We find great heterogeneity in the controls: 49 of the 80 controls were on beta blockade and
only 11 controls had a stress test. This is an unacceptable error because it divides the control group into 4 sub-
groups but the authors of the study club all four together for comparison. We have no idea of this break up. The only
fair comparison for the study group (no stress test, only beta blockade) would have been the fraction of the control
group with stress testing and beta blockade. Additionally, in a case control study, each member of the study group
must be matched against one or more case controls. We are told that the authors were able to find matches for only
80 of the 100 needed. Another serious systematic error.

MEASUREMENT
Measurement error
Device used Device error Observer error
Gold std.

Device suited to task

Training

Scoring

Blinding
Repetition

Protocols

Y ? N

1.Target heart rate Y N Y N N - -

2.Revised cardiac index score Y N Y N N Y -
3.Eagle index Y N Y N N Y -
4.Adverse cardiac events: Unstable angina/ MI/ Y - - N Y N -
arrhythmia/ cardiac death

Measurement bias: Nothing to complain about.

© Dr Arjun Rajagopalan