Transcript Slide 1

Perioperative care: beta blockers
and a little beyond
Deepti Rao
Objectives
• Recognize ACC/AHA guidelines for cardiac risk
assessment
• Understand the controversy surrounding the
use of perioperative beta blockers
• Understand the complexities and tools used to
make decisions regarding perioperative
management of antithrombotic therapy
Cardiac evaluation and care algorithm
for noncardiac surgery
Major predictors that require intensive management
and may lead to delay in or cancellation of the
operative procedure--per ACC/AHA guideline summary
 Unstable coronary syndromes including unstable
or severe angina or recent MI
 Decompensated heart failure including NYHA
functional class IV or worsening or new-onset HF
 Significant arrhythmias including high grade AV
block, symptomatic ventricular arrhythmias,
supraventricular arrhythmias with ventricular rate
> 100 bpm at rest, symptomatic bradycardia, and
newly recognized ventricular tachycardia
 Severe heart valve disease including severe
aortic stenosis or symptomatic mitral stenosis
Cardiac evaluation and care algorithm
for noncardiac surgery
ACC/AHA guideline summary: Cardiac risk stratification
for noncardiac surgical procedures
High risk (reported risk of cardiac death or nonfatal myocardial infarction [MI] often)
Aortic and other major vascular surgery
Peripheral arterial surgery
Intermediate risk (reported risk of cardiac death or nonfatal MI generally 1 to 5
percent)
Carotid endarterectomy
Head and neck surgery
Intraperitoneal and intrathoracic surgery
Orthopedic surgery
Prostate surgery
Low risk* (reported risk of cardiac death or nonfatal MI generally less than 1 percent)
Ambulatory surgery
Endoscopic procedures
Superficial procedure
Cataract surgery
Breast surgery
Cardiac evaluation and care algorithm
for noncardiac surgery
Estimated energy requirements for
various activites
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Take care of self
Eat, dress, use toilet
Walk indoors around the house
Walk a block or 2 on level ground
Do light work around the house like dusting or washing the
dishes
Climb a flight of stairs or walk up a hill
Walk on level ground at 4 mph
Run a short distance
Do heavy work around the house like scrubbing floors
Participate in moderate activities like golf or dancing
Participate in strenuous activities like swimming or skiing
Cardiac evaluation and care algorithm
for noncardiac surgery
Revised Goldman cardiac risk index (RCRI)
Six independent predictors of major cardiac complications
High-risk type of surgery (includes any intraperitoneal,
intrathoracic, or suprainguinal vascular procedures)
History of ischemic heart disease (history of MI or a positive
exercise test, current complaint of chest pain considered to
be secondary to myocardial ischemia, use of nitrate
therapy, or ECG with pathological Q waves; do not count
prior coronary revascularization procedure unless one of
the other criteria for ischemic heart disease is present)
History of compensated or prior HF
History of cerebrovascular disease
Diabetes mellitus requiring treatment with insulin
Preoperative serum creatinine >2.0 mg/dL (177 mol/L)
Cardiac evaluation and care algorithm
for noncardiac surgery
Perioperative beta blockers
• Perioperative cardiac ischemia
– 1-10% of patients older than 50
– Causes
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Increased inflammatory mediators
increased sympathetic tone, catecholamine surge
oxygen supply/demand mismatch in heart
Hypercoagulability and decreased fibrinolytic activity
Acute plaque rupture, thrombosis and occlusion
How do we prevent this?
Perioperative beta blockers
• How do they work?
– Decrease cardiac oxygen demand
– Antiarrhythmic
– Limit sympathetic and neuroendocrine responses
to stress
– May limit free radical production/inflammation
Perioperative Beta blockers
• 1970’s, 1980’s,1990’s
• Small trials showing bb reduced risk of periop
cardiac events in selected patients with known
or suspected cardiac events
• Use endorsed by Leapfrog group, AHRQ and
National Quality Forum
The effect of Bisoprolol on Perioperative Mortality and
Myocardial Infarction in High-Risk Patients Undergoing Vascular
Surgery—DECREASE
• Poldermans, et al 1999
• Randomized 112 “high risk” patients to either
standard care or standard care plus bisoprolol
– High risk: Risk factors and positive dobutamine
echo
– Not blinded except to adverse events
committee/no placebo
• Undergoing major vascular surgery
The effect of Bisoprolol on Perioperative Mortality and
Myocardial Infarction in High-Risk Patients Undergoing Vascular
Surgery—DECREASE
• Started bisoprolol at doses of 5mg, increased to
10mg if heart rate >60 bpm 1 week later.
• Started bisoprolol average of 37 days prior to
surgery (!!!!!!), at least 1 week prior
• In hospital
– If symptoms or signs of perioperative mi with
tachycardia developed, patients received beta-bl (4)
– If unable to take bisoprolol postop, heart rate
monitored q1hr and given metoprolol iv if hr>80 bpm
– Medication withheld if hr<50 bpm or sbp<100 mmhg
The effect of Bisoprolol on Perioperative Mortality and
Myocardial Infarction in High-Risk Patients Undergoing Vascular
Surgery—DECREASE
• Followed patients for 30 days postop
• 12 lead EKG and ck-mb days 1,3,7 postop
The effect of Bisoprolol on Perioperative Mortality and
Myocardial Infarction in High-Risk Patients Undergoing Vascular
Surgery—DECREASE
• For death from cardiac cause:
– AAR 13.6%
– RRR 80%
– NNT 7
• For nonfatal MI: (no events in bisoprolol
group)
– AAR 17%
– NNT 6
The effect of Bisoprolol on Perioperative Mortality and
Myocardial Infarction in High-Risk Patients Undergoing Vascular
Surgery—DECREASE
• On the basis of our results, we recommend that
high-risk surgical patients receive beta-blockers perioperatively,
beginning one to two weeks before surgery.
The goal should be to reduce the heart rate to
less than 70 beats per minute preoperatively and to
less than 80 beats per minute in the immediate postoperative
period. Therapy should be continued for
at least two weeks postoperatively.
• An alternative to
this approach would be to omit preoperative noninvasive
cardiac testing and prescribe a beta-blocker perioperatively
for all patients with clinical risk factors
who are undergoing high-risk surgery.
• Although our
results applied to patients who were undergoing major
vascular surgery, we recommend that high-risk
patients undergoing other types of noncardiac surgery
receive a beta-blocker perioperatively.
The effect of Bisoprolol on Perioperative Mortality and
Myocardial Infarction in High-Risk Patients Undergoing Vascular
Surgery—DECREASE
• So what are some of the problems with the
study?
Early Beta-blocker trials
• Small in size (63-200)
• Used surrogate end points
• Study designs were flawed (cohort, unblinded,
retrospective)
Perioperative beta-blocker therapy and
mortality after major noncardiac surgery
• Lindenauer, et al 2005
• Retrospective cohort study
• Used data from Premier’s Perspective,
database of small to mid sized nonteaching
hospitals
• Adults undergoing major noncardiac surgery
• Compared those who received beta-blockers
in first 1-2 days hospitalization vs. not
Perioperative beta-blocker therapy and
mortality after major noncardiac surgery
• 663,635 eligible patients, 122,338 received
beta-blockers
Perioperative beta-blocker therapy and
mortality after major noncardiac surgery
Perioperative beta-blocker therapy and
mortality after major noncardiac surgery
• No significant benefit of perioperative betablockade until approx 3 RCRI
• What are some problems with this trial?
Recent trials-preop initiation of beta
blockade in intermediate risk patients
• Metoprolol after Vascular Surgery (MaVS)
– No difference in cardiac events
– Increase bradycardia and hypotension requiring
treatment
• Diabetic Post Operative Mortality and
Morbidity
• Perioperative Beta Blockade (POBBLE)
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
• Devereaux, et al 2008
• POISE (PeriOperative Ischemic Evaluation)
• Small non-cardiac surgery trials suggested that β blockers might
reduce the occurrence of major cardiovascular events, although
these trials had methodological limitations.
• Recent, moderate sized randomised controlled trials of
perioperative β blockers did not demonstrate benefit.
• To further investigate the effects of perioperative β-blocker therapy,
a randomised controlled trial comparing the effect of extendedrelease metoprolol succinate 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.
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
• 8351 patients with or at risk for
atherosclerotic disease
• Patients treated with metoprolol extended
release
– First dose 2-4 hours prior to surgery (100 mg)
– Within 6 hours post op (100mg)
– 12 hours after surgery (200mg/day)
– If could not take po, iv metoprolol given
– Continued for 30 days
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
• Ekg 6-12 hours postop and days 1,2,30
• Ck/mb or troponin 6-12 hours postop and
days 1,2,3
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
• Primary endpoint—cardiovascular death, nonfatal mi, nonfatal
cardiac arrest
– ARR 1.1%
– RRR 16%
– NNT 90
• MI
– ARR 1.5%
– RRR 26%
– NNT 66
• CVA
– NNH 125
• Death
– NNH 200
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
Our results suggest that for every 1000 patients with a similar risk profile
undergoing non-cardiac surgery extended-release metoprolol would prevent:
• 15 patients from having a myocardial infarction,
• 3 from undergoing cardiac revascularisation,
• 7 from developing new clinically significant atrial fibrillation.
The results also suggest that extended-release metoprolol would result in:
• 8 deaths,
• 5 patients having a stroke,
• 53 experiencing clinically significant hypotension, and
• 42 experiencing clinically significant bradycardia
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
Our results highlight the risk in assuming a perioperative
β-blocker regimen has benefit without substantial
harm before the availability of a large randomised
controlled trial establishing such findings.
Our post-hoc multivariate analyses suggest that
clinically significant hypotension, bradycardia, and stroke
explain how β blockers increased the risk of death in this
trial.
Sepsis or infection was the only cause of death that
was significantly more common among patients in the
metoprolol group than in those in the placebo group.
Effects of extended-release metoprolol succinate
in patients undergoing non-cardiac surgery
• What are some of the problems with this
trial?
Perioperative Beta blockers
• Many of the recent systematic reviews on this
topic are “overwhelmed” by the POISE trial,
include early trials which are of poor quality,
and hampered by the variety of beta blocker
chosen and protocol.
So what now?
2009 ACCF/AHA Focused Update on
Perioperative Beta Blockade
Class 1 recommendations
Beta blockers should be continued in patients
undergoing surgery who are receiving beta
blockers for treatment of conditions with
ACCF/AHA Class I guideline indications for the
drugs. (Level of Evidence: C)
2009 ACCF/AHA Focused Update on
Perioperative Beta Blockade
Class IIa Recommendations
• Beta blockers titrated to heart rate and blood
pressure are probably recommended for patients
undergoing vascular surgery who are at high
cardiac risk owing to coronary artery disease or
the finding of cardiac ischemia on preoperative testing (4,5). (Level of Evidence: B)
• Beta blockers titrated to heart rate and blood
pressure are reasonable for patients in whom
preoperative assessment for vascular surgery
identifies high cardiac risk, as defined by the
presence of more than 1 clinical risk factor.* (Level of Evidence: C)
• Beta blockers titrated to heart rate and blood
pressure are reasonable for patients in whom
preoperative assessment identifies coronary
artery disease or high cardiac risk, as defined by
the presence of more than 1 clinical risk factor,*
who are undergoing intermediate-risk surgery (6). (Level of Evidence: B)
2009 ACCF/AHA Focused Update on
Perioperative Beta Blockade
• So only those patients already on beta-blockade
or those of high risk who can have their betablocker titrated to effect
• Why? We are not sure how to use safely.
– Patient (low vs high risk)
– Type of beta blocker (high beta-1 selectivity)
– Dose
• Heart rate control without hypotension
– Timing of initiation
• Anti-inflammatory and plaque stabilizing properties may
take days to develop
Surveillance and diagnosis of
perioperative mi
• Per ACC guidelines:
– In patients with high or intermediate clinical risk
and undergoing high or intermediate risk surgery
• ECG postop, day 1 and day2
– In patients without documented CAD:
• Only those with perioperative cardiac dysfunction
Managing the patient on warfarin undergoing an
elective surgery---from Jaffer, talk
Patient risk factors
1. Indication
2. RF for
Thromboembolism
Surgical risk factors
1. Type of surgery
2. Risk of Bleeding
3. Risk of thromboembolism
4. Time off anticoag
Weigh the consequences of TE and Bleeding
Determine the need for bridging therapy
Is interruption of my patient’s
antithrombotic therapy necessary?
• Low risk of bleeding for which coumadin can
be continued:
– Minor dental procedures
– Minor dermatologic procedures
– Cataract removal
– Arthrocentesis
– EGD/colonoscopy with or without biopsy
Managing the patient on warfarin undergoing an
elective surgery---from Jaffer, talk
Patient risk factors
1. Indication
2. RF for
Thromboembolism
Surgical risk factors
1. Type of surgery
2. Risk of Bleeding
3. Risk of thromboembolism
4. Time off anticoag
Weigh the consequences of TE and Bleeding
Determine the need for bridging therapy
Suggested Patient Risk Stratification for Perioperative Arterial or Venous
Thromboembolism
Risk Stratum
Mechanical Heart
Valve
High
Any mitral valve
prosthesis
Older (caged-ball or
tilting disc) aortic
valve prosthesis
Recent (within 6
mo) stroke or
transient ischemic
attack
Atrial Fibrillation
CHADS2 score
of 5 or 6
Recent (within 3
mo) stroke or
transient
ischemic attack,
Rheumatic
valvular heart
disease
VTE
Recent (within 3
mo) VTE
Severe
thrombophilia (eg,
deficiency of
protein C, protein S
or antithrombin,
antiphospholipid
antibodies, or
multiple
abnormalities)
Suggested Patient Risk Stratification for Perioperative Arterial
or Venous Thromboembolism
Risk Stratum
Mechanical Heart
Valve
Atrial Fibrillation
VTE
Moderate
Bileaflet aortic
valve prosthesis
and one of the
following: atrial
fibrillation, prior
stroke or transient
ischemic attack,
hypertension,
diabetes,
congestive heart
failure, age > 75 yr
CHADS2 score of 3
or 4
VTE within the past
3 to 12 mo
Nonsevere
thrombophilic
conditions (eg,
heterozygous factor
V Leiden mutation,
heterozygous factor
II mutation)
Recurrent VTE
Active cancer
(treated within 6
mo or palliative)
Suggested Patient Risk Stratification for Perioperative Arterial
or Venous Thromboembolism
Risk Stratum
Mechanical Heart
Valve
Atrial Fibrillation
VTE
Low
Bileaflet aortic
valve prosthesis
without atrial
fibrillation and no
other risk factors
for stroke
CHADS2 score of 0
to 2 (and no prior
stroke or transient
ischemic attack)
Single VTE occurred
> 12 mo ago and no
other risk factors
Managing the patient on warfarin undergoing an
elective surgery---from Jaffer, talk
Patient risk factors
1. Indication
2. RF for
Thromboembolism
Surgical risk factors
1. Type of surgery
2. Risk of Bleeding
3. Risk of thromboembolism
4. Time off anticoag
Weigh the consequences of TE and Bleeding
Determine the need for bridging therapy
What is the procedural risk of
bleeding?
• High Bleeding Risk:
– CABG or valve replacement surgery
– Intracranial or spinal surgery
– AAA repair, peripheral artery bypass, and other major
vascular surgery
– Major orthopedic surgery such as hip or knee
replacement
– Reconstructive plastic surgery
– Major cancer surgery
– Prostate and bladder surgery
What is the procedural risk of bleeding?
• Perioperative anticoagulation should be
undertaken with caution:
– Resection of colonic polyps esp sessile polyps>2
cm in diameter
– Biopsy of prostate or kidney
– Cardiac pacemaker or defibrillator implantation
Managing the patient on warfarin undergoing an
elective surgery---from Jaffer, talk
Patient risk factors
1. Indication
2. RF for
Thromboembolism
Surgical risk factors
1. Type of surgery
2. Risk of Bleeding
3. Risk of thromboembolism
4. Time off anticoag
Weigh the consequences of TE and Bleeding
Determine the need for bridging therapy
Perioperative risk of TE
• Rate of TE approx 1.6%
– Risk of VTE 100 fold greater during the perioperative
period relative to the nonoperative period
• Surgical milieu induces a hypercoagulable state
• However major bleeding is also an issue approx
3%
– Full dose bridging leads to 4-6 fold increase in major
bleeding…wait couple of days prior to starting full
dose and just use prophylactic dose?
How do I balance the risk of thromboembolism
with the risk of bleeding?
• Art of medicine
• On coumadin for afib undergoing CABG vs on
coumadin for mitral valve replacement
undergoing lap chole
Managing the patient on warfarin undergoing an
elective surgery---from Jaffer, talk
Patient risk factors
1. Indication
2. RF for
Thromboembolism
Surgical risk factors
1. Type of surgery
2. Risk of Bleeding
3. Risk of thromboembolism
4. Time off anticoag
Weigh the consequences of TE and Bleeding
Determine the need for bridging therapy
. If I do have to interrupt my patient’s antithrombotic
therapy, should I recommend bridging therapy?
• Based on risk of embolism from table above
suggeted regimens for bridging:
– High
• Therapeutic SC LMWH
• IV UFH
– Moderate
• Therapeutic SC LMWH
• IV UFH
• Low dose SC LMWH
– Low
• Low dose SC LMWH
• none
Other bridging issues
• Many bridging protocols
– Jaffer, et al. CCM 2003;70:973
• If want to eliminate any residual antithrombotic effect
stop
–
–
–
–
–
vka 5 days prior to procedure,
LMWH 24 hours prior
asa 7-10 days (could make argument 2-3 days)
nsaids 24 hours (no increased risk bleeding with cox-2)
clopidogrel 5-7 days prior
• In resuming antithrombotic therapy with LMWH wait
until hemostasis is obtained
Other bridging issues
• Time to activity of antithrombotic therapy:
– Warfarin 2-3 days
– LMWH 3-5 hours for peak effect
– ASA minutes
– Clopidogrel 3-7 days