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Noncardiac Surgery
Lessons from DECREASE-IV
M Chadi Alraies, MD
Department of Hospital Medicine Grand Round
Cleveland Clinic Foundation
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Agenda
• Perioperative cardiac events
• RCRI
• ACC/AHA Guidelines for perioperative BB use.
• What is already known about perioperative β-
blockers
• Literature review
• DECREASE-IV study
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Introduction
• About 20 million Americans undergo surgery
with general anesthesia each year.1
• Cardiac events (MI or Cardiac death) result in
perioperative mortality rate of 3-6%
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Incidence of Perioperative Myocardial Infarction After Noncardiac Surgery
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Perioperative cardiac events
• The most common reason for preoperative
evaluation.
• Associated with increased mortality and
results in higher costs
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Prognosis of perioperative MI after noncardiac surgery
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Pathophysiology of Perioperative MI
• Multifactorial
• Myocardial oxygen demand/supply mismatch
due to:
– Perioperative surgical stress
– Tachycardia
– Hypertension
– Pain
• Coronary plaque instability and subsequent
rupture also lead to infarction.
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ACC/AHA 2007 Guidelines on
Perioperative Cardiovascular Evaluation
and Care for Noncardiac Surgery
Rate of cardiac death, nonfatal myocardial infarction, and nonfatal cardiac arrest
according to the number of predictors ¥
No risk factors - 0.4 percent (95% CI 0.1-0.8 percent)
One risk factor - 1.0 percent (95% CI 0.5-1.4 percent
Two risk factors - 2.4 percent (95% CI 1.3-3.5 percent
Three or more risk factors - 5.4 percent (95% CI 2.8-7.9 percent)
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Applying Classification of
Recommendations and Level of Evidence
Level A Class I Class IIa Class IIb Class III
CLASS IIa
• For patients undergoing vascular surgery with or without
clinical risk factors, statin use is reasonable. (B)
CLASS IIb
• For patients with at least 1 clinical risk factor who are
undergoing intermediate-risk procedures, statins may be
considered. (C)
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Mechanism of Beta-blockers?
• Decrease myocardial oxygen demand
– Heart rate
– Myocardial contractility
• Reduce the adrenergic activity
• Reduce levels of free fatty acid
• Increase myocardial glucose uptake
• Coronary plaque stability – requires weeks
– Anti-inflammatory
– Progression of atherosclerosis
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● Most trials are inadequately powered.
● Few randomized trials of medical therapy to prevent
perioperative MACE have been performed.
● Few randomized trials have examined the role of perioperative
beta-blocker therapy, and there is particularly a lack
of trials that focus on high-risk patients.
● Studies to determine the role of beta blockers in
intermediate- and low-risk populations are lacking.
● Studies to determine the optimal type of beta blockers are
lacking.
● No studies have addressed care-delivery mechanisms in the
perioperative setting, identifying how, when, and by whom
perioperative beta-blocker therapy should be implemented
and monitored.
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Review of literature
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Effect of Atenolol on Mortality and Cardiovascular
Morbidity after Noncardiac Surgery. Mangano 1996
Mangano DT, Layug EL, Wallace A, et al; for Multicenter Study of Perioperative Ischemia Research Group. Effect of atenolol on mortality and
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cardiovascular morbidity after noncardiac surgery. N Engl J Med. 1996;335:1713–1720. 19
Mangano 1996
83%
68%
P = 0.008
Overall Survival in the Two Years after Noncardiac Surgery among 192 Patients in the Atenolol and
Placebo Groups Who Survived to Hospital Discharge.
90%
79%
Event-free Survival in the Two Years after Noncardiac Surgery among 192 Patients in the Atenolol
and Placebo Groups Who Survived to Hospital Discharge. N Engl J Med. 1996;335:1713–1720.
Poldermans D, Boersma E, Bax JJ, et al; for Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography
Study Group. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular
surgery. N Engl J Med. 1999;341: 1789–1794.
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Poldermans D,1999
Kaplan–Meier Estimates of the Cumulative Percentages of Patients Who Died of Cardiac Causes
or Had a Nonfatal Myocardial Infarction during the Perioperative Period.
Auerbach AD, Goldman L. Beta-Blockers and reduction of cardiac events in noncardiac surgery: scientific review. JAMA. 2002;287:1435–1444
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1. β-blockers work the best in high risk patients.
2. Need more studies for patients with stable coronary
disease and are undergoing elective surgery?
3. What is the optimal duration of therapy?
4. Which agent is the best?
5. When to start BB therapy?
Brady AR, Gibbs JS, Greenhalgh RM, et al. Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular
surgery: results of a randomized double-blind controlled trial. J Vasc Surg. 2005;41:602– 609.
28
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POBBLE trial 2005
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The effects of perioperative betablockade: results of
the Metoprolol after Vascular Surgery (MaVS) study, a
randomized controlled trial. Yang et al 2006
Yang H, Raymer K, Butler R, et al. The effects of perioperative betablockade: results of the Metoprolol after Vascular Surgery (MaVS) study, a
randomized controlled trial. Am Heart J. 2006;152:983–990 30
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Outcomes at 30 days postoperative
Juul AB, Wetterslev J, Gluud C, et al. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery:
randomized placebo controlled, blinded multicentre trial. BMJ. 2006;332:1482. 35
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Kaplan-Meier plot of time to primary outcome measure
Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE
trial): a randomized controlled trial. Lancet. 2008;371:1839 –1847. 38
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PeriOperative Ischemia Evaluation (POISE)
8351 patients.
Participants Hx: CAD, PVD, CVA, CHF within 3 yrs of surgery, or vascular
surgery
Surgery Major non-cardiac surgery – majority vascular surgeries
Mean age 69 yrs
8351 Patients
Hx: CAD, PVD, CVA, CHF
Major vascular surgery
4174 Patients
Metoprolol XL 100mg 2-4 hours 4177 Patients
before surgery and Placebo
200mg/day for 30 days
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Devereaux PJ,. Lancet. 2008;371:1839 –1847.
Kaplan-Meier estimates of
the primary outcome (A), myocardial infarction (B), stroke (C), and death (D)
MIs
Primary
MIs
Primary
Death
Strokes
Strokes
Death
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Devereaux et al. POISE . Lancet. 2008;371:1839 –1847.
PeriOperative Ischemia Evaluation (POISE)
BB prevents
15 MI
3 Revasc
7 Atrial Fib
BB causes:
8 Deaths
5 Stroke (1.0% vs. 0.5%, HR 2.17, p = 0.005)
53 Hypotension (15.0% vs. 9.7%, p < 0.0001)
42 Bradycardia (6.6% vs. 2.4%, p < 0.0001)
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Devereaux et al. POISE . Lancet. 2008;371:1839 –1847.
POISE observations
• BB decreased non-fatal MI and CV mortality
• Evidence does not support initiation of BB in
most pts undergoing surgery with (RCRI <3)
• Benefit of BB for:
– High risk patients (RCRI 3+)
– Pts with evidence of ischemia by stress testing
• However, most patients at highest CV risk
have independent indications for B-B therapy
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POISE limitations
• Significant hypotension more often in BB
group (15% vs. 9.7%)
• Fixed dose, not titrated
• Started treatment only 2-4 hrs prior to surgery
• High starting dose of oral metoprolol may
have contributed to hypotension/stroke rate.
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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)
Dunkelgrun M, Boersma E, Schouten O, Koopman-van Gemert AW, van Poorten F, Bax JJ,
Thomson IR, Poldermans D; Dutch Echocardiographic Cardiac Risk Evaluation Applying
Stress Echocardiography Study Group.
Departments of Vascular Surgery, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Objective
• This study evaluated the beta-blockers and
statins for the prevention of perioperative
cardiovascular events in intermediate-risk
patients undergoing noncardiovascular
surgery.
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Questions
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