Transcript Journal Club

Journal Club
Lei Zhang PGY 3
7/16/09
Case
• 55 y.o. F, PMH HTN, DM, TIA, and
diverticulosis
• Had multitple diverticulitis, lower GIB in
the past
• Scheduled to have elective colon resection
in 2 wks
• Presented to the office for pre-op
clearance
• Denied CP, SOB, swelling
Case
• HTN well controlled with Lisinopril and
HCTZ
• DM well controlled with Glipizide and
Metformin
• Also taking ASA and Zocor
• Good functional status, able to climb 2
flight of stairs carrying grocery
• Recent EKG/CXR within normal limits
• Recent CBC, Chem 7 within normal limits
Anything Else Needed
Pre-operatively?
Add Beta-blocker?
Perioperative Beta
Blocker use
• Circulation, 2006
• Feringa and colleagues performed an
observational cohort study of 272 vascular
surgery patients
• Higher doses of -blockers and tight heart
rate (< 70 bpm) control associated with
reduced perioperative myocardial ischemia
and troponin release and improved longterm outcome
Perioperative Beta
Blocker use
• J AM Coll Cardio, 2006
• Poldermans and colleagues randomly
assigned 770 intermediate-risk patients to
cardiac stress testing (n386) or no testing
(n384) preoperatively
• Concluded that cardiac testing can safely
be omitted in intermediate-risk patients if
beta blockers aimed at tight heart rate
control are prescribed
Perioperative Beta
Blocker use
• BMJ, 2005
• Donald Redelmeier & colleague performed
retrospective cohort study in Canada in
37,151 asymptomatic patients older than
65 admitted for elective surgery (mainly
abd & ortho procedure)
• Patients receiving long-acting betablockers have lower perioperative cardiac
risk than short-acting agent
ACC/AHA Guideline for
Pre-op Beta-blocker Use
Perioperative Beta
Blocker use
• Am Heart J. 2006
• Yang & colleague performed a double-blind
randomized controlled trial of perioperative
metoprolol versus placebo in 496 patients
undergoing vascular surgery
• Metoprolol was not effective in reducing the 30day & 6-month postop cardiac event rates.
• Concluded that prophylactic use of perioperative
beta-blockers in all vascular patients is not
indicated
Perioperative Beta
Blocker use
• BMJ, 2006
• Anne Benedicte Juul & colleague designed a
randomized, controlled and blinded multicentre
trial in 921 diabetic patients, age > 39, scheduled
for major non-cardiac surgery
• 100 mg metoprolol extended release or placebo
given from the day before surgery to a max of 8
perioperative days
• Conclusions: Perioperative metoprolol did not
significantly affect mortality and cardiac
morbidity
Perioperative Beta
Blocker use
• BMJ, 2006
• Devereaux & colleague published a metaanalysis of randomized controlled trials in
non-cardiac surgery pts
• β blockers might prevent major
cardiovascular events but increase the risk
of hypotension & bradycardia
Peri-operative Use of
Beta-blocker
Yes or NO
POISE TRIAL
• PeriOperative ISchemic Evaluation
• Purpose of the trial:
– Comparing the effect of extendedrelease metoprolol with that of placebo
on 30-day risk of major cardiovascular
events in patients with, or at risk of,
atherosclerotic disease who were
undergoing non-cardiac surgery.
POISE TRIAL
• Research question
– Does peri-operative β-blocker
regimen benefit noncardiac surgery
pts without substantial harm?
• Double-blinded, randomized,
controlled, multi-center trial
POISE TRIAL
• Involved 8,351 pts and 190 hospitals in
23 countries
• Study period 10/2002 – 7/2007
• Ethical approval for all participating
sites obtained
• Written informed consent obtained
from all pts
POISE TRIAL
• Inclusion criteria
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–
–
–
undergoing non-cardiac surgery
aged 45 years or older
expected length of hospital stay > 24 h
any one of the following criteria
• hx of CAD
• hx of PVD
• Stroke
POISE TRIAL
• hospitalization for CHF within past 3 years
• undergoing major vascular surgery
– Or, any three of seven risk criteria
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•
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•
•
•
undergoing intrathoracic or intraperitoneal surgery
hx of CHF
hx of TIA
hx of diabetes
creatinine >175 μmol/L ( >2.0 mg/dL)
age >70 years
undergoing emergent or urgent surgery
POISE TRIAL
• Exclusion criteria
–
–
–
–
–
–
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HR < 50 bpm
2nd or 3rd AVB
Asthma
Receiving β blocker or planned to start one
perioperatively
Prior adverse reaction to β blocker
CABG in the preceding 5 years with no ischemia
Low-risk surgical procedure
On verapamil
POISE TRIAL
• Patients were randomly assigned to
two groups via a 24-h computerized
randomization phone service
• Participants, health-care providers,
data collectors, and outcome
adjudicators were masked to
treatment allocation
Trial Profile…
Figure 1
Table 2
Method
• 1st dose of the study drug (ie, oral
extended-release metoprolol 100 mg
or matching placebo) given 2–4 h
before surgery
• VS checked each time before
medication to ensure HR > 50 bpm &
SBP > 100 mm Hg
Method
• Within 6 h postop, pt received 1st post-op
dose
• 12 h after 1st post-op dose, start
Metoprolol extended-release 200mg or
placebo p.o. daily for 30 days
• If HR <45bpm or SBP < 100, study drug
withheld until recovered
• Study drug was then restarted at 100mg
daily
Method
• If HR consistently 45–49 bpm, SBP
>100 mm Hg, delayed taking the study
drug for 12 h
• If unable to take p.o., study drug
given by slow or rapid IV infusion q6h
• Investigators were allowed to select
either the slow or rapid IV infusion
Method
• Slow infusion
– 15 mg of study drug in 25 mL NS over
60 min
– HR & BP checked at 10, 30, and 60 min
into the infusion
• If HR/BP drop, study drug reduce to
10mg
Method
• Rapid infusion
– 5 mg of the study drug IV over 2 min and
repeated every 5 min for a total of 15 mg
• ECG recorded 6–12 h postoperatively and
on the 1st, 2nd , and 30th days
• Troponin or CK-MB at 6–12 h
postoperatively & on the 1st , 2nd , and 3rd
days
POISE TRIAL
• Primary outcome
– cardiovascular death
– non-fatal MI
– non-fatal cardiac arrest at 30 days
Statistical Analysis
• Study has 85% power to detect a
relative risk reduction of 25%
• All analyses used Cox proportional
hazards models
Table 3
Results
• Fewer in the metoprolol group reached
the primary endpoint (hazard ratio 0·84,
95% CI 0·70–0·99, p=0·039)
• Fewer patients in the metoprolol group had
a non-fatal MI (hazard ratio 0·70, 95% CI
0·57–0·86; p=0·0008)
• Fewer in the metoprolol group had cardiac
revascularisation or developed new A fib
Result
• More in the Metoprolol group had a stroke
(hazard ratio 2·17, 95% CI 1·26–3·74,
p=0·0053)
• More people receiving metoprolol died
(1·33, 1·03–1·74, p=0·0317)
• More pts receiving Metoprolol had
significant hypotension and bradycardia
Figure 2
MIs
Primary
Strokes
Death
Results
• Median length of hospital stay was 8
(IQR 4–14) days in the Metoprolol
group and 8 (4–15) days in the
placebo group (p=0·4046)
• The number of nights spent in
ICU/CCU was much the same in the
two groups
Results
• At discharge, Metoprolol group had
– a lower mean HR(71·6 [SD 12·0]vs 78·6
[11·8]; p<0·0001)
– lower mean SBP & DBP (129 [18·9]/72
[11·1] vs 131 [18·2]/74 [11·1]mm Hg;
p<0·0001)
Discussion
• Why extended-release Metoprolol
have increased risk of death and
stroke?
• Clinically significant hypotension,
bradycardia and stroke contribute to
the increasing risk of death
Table 5
Discussion
• Sepsis or infection was the only
cause of death that was significantly
more common in Metoprolol group
• Hypotension caused by β blockers
could have predisposed pts to
developing nosocomial infection
Discussion
• β blockers suppress tachycardia
could delay the recognition of sepsis
and infection, therefore delaying
treatment, which might increase the
risk of death
Discussion
• Pts receiving β-blocker who develop
sepsis or infection might not have
the capacity to mount enough
response to sustain life or allow
adequate delivery of antibiotics to
tissue
Discussion
• POISE researchers also performed
several meta-analysis of trials of
periop Beta-blocker use
– Decrease risk of non-fatal MI
– Increase risk of death
– Increase risk of non-fatal stroke
Figure 4
Conclusion
Summary
• Are the results valid?
– Yes
• Are the results important?
– Yes
• Can you apply the results to your
patient?
– Yes
Validity
• This is a large, multi-center,
randomized, double-blind, controlled
clinical trial
• Both groups were comparable in
terms of back ground information,
type of surgery, anesthesia, and
medications
• Both groups were treated equally
Validity
• Confounding criteria were well-accounted
between the two groups
• Clear inclusion and exclusion criteria
• Study has detailed medication
administration and side-effect monitoring
protocol
• Follow-up was complete for majority of pts
Validity
• Although involving large of amount of pts
and study personnel from 190 hospitals in
23 countries, the study was well regulated
by central and on-site monitoring system
• Problems found in Iran and Colombia were
caught immediately and data excluded
from the study
Applicability
• This is a large multi-country study,
involving different racial, ethnic &
economic population; it is safe to
generalized the study results to our
practice patients
Significance
• The study have enormous influence
on current medicine practice
• It challenged the currently popular
concept of perioperative Betablocker use
Significance
• For every 15 patients in POISE trial,
one had a cardiovascular death, nonfatal myocardial infarction, non-fatal
cardiac arrest, or non-fatal stroke at
30-day follow-up
Significance
• Suggest that the addition of
perioperative Beta-blocker
potentially has serious risks
• Lead to the further question of who
will benefit from Beta-blocker and
who will not?
Thank You
ACC/AHA Guideline for Preop
Eval for Noncardiac Surgery
• Pts with active cardiac conditions,
indicate major clinical risk
– unstable coronary syndromes,
• acute MI < 7 days
• recent MI > 7 days but </= 1 month with evidence of
ischemia
• unstable or severe angina
– decompensated heart failure,
– significant arrhythmias
– severe valvular disease
ACC/AHA Guideline for Preop
Eval for Noncardiac Surgery
• Pts with clinical risk factors
– history of heart disease,
• hx MI or Q waves by ECG
– history of compensated or prior CHF
– history of cerebrovascular disease, TIA,
stroke
– diabetes mellitus, preop use of insulin
– renal insufficiency, preop Cr >2.0