department of o utcomes r esearch. perioperative myocardial infarction daniel i. sessler, m.d....
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Department of OUTCOMES RESEARCH
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Perioperative Myocardial Infarction
www.or.org
Daniel I. Sessler, M.D.
Michael Cudahy Professor and ChairDepartment of OUTCOMES RESEARCH
Cleveland Clinic
No personal financial interestsrelated to this presentation
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Perioperative Mortality
Intraoperative mortality rare
Thirty-day postoperative mortality•1% nationwide in United States•2% worldwide for inpatients ≥45 years old•80% during initial hospitalization
Mostly cardiovascular or consequent
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Causes of Death
Bartels, et al., 2013, Anesthesiology
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Postoperative MIs are Common≈230 million non-cardiac operations / year
MI incidence 8% among inpatients >45 years•≈10 million postoperative infarctions per year
Nearly all non-ST segment elevation•Plaque rupture?•Supply-demand mismatch?•Thrombus?
Postoperative MI poorly understood•Etiology?•Prediction?•Prevention? (today’s focus)•Treatment?
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Silent and Deadly
Most MIs only detected by troponin•Only 15% report chest pain•65% entirely asymptomatic
Mortality identical after apparent & silent MIs•It’s not just “troponitis”
Mortality is 10% at 30 days•Twice as high as non-operative infarctions
–Different?–Unrecognized?–Untreated? VISION: Devereaux JAMA 2012
and Botto, Anesthesiology 2014
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Troponin T Predicts Mortality
“Prognosis define diagnosis”
Even slight troponin elevations predict death•Population attributable risk = 34%
Peak Troponin (ng/ml)
30-day Mortality (%)
Time to death (days)
<0.01 1 —
0.02 4 13
0.03-0.29 9 9
≥0.3 17 6
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MINS (Troponin Increase)
Outcome No MINS(n = 13,822), %
MINS(n = 1,194), %
OR (95% CI)
Nonfatal cardiac arrest
0.1 0.8 14.6 (5.7-37.0)
CCF 1.0 9.4 10.3 (8.0-13.4)
Stroke 0.4 1.9 4.7 (2.9-7.6)
Death 1.1 9.8 10.1 (7.8-13.0)
Composite 2.4 18.8 9.6 (8.0-11.5)
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Universal Definition of MI*
“Most patients who have a perioperative MI will not experience ischemic symptoms. Nevertheless, asymptomatic perioperative MI is as strongly associated with 30-day mortality as symptomatic MI. Routine monitoring of cardiac biomarkers in high-risk patients … after major surgery is therefore recommended.”
*Thygeson, Circulation 2012
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Elevated Troponin?
Cardiology consult•Some patients need catheterization ± angioplasty•Discussion of risk
Aspirin ± statins
Heart rate and hypertension control
Lifestyle•Smoking cessation•Reasonable diet•Exercise
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ENIGMA-2
Background•N2O increases plasma homocysteine
•N2O impairs endothelial function
Hypothesis•N2O increases 30-day death or major CV events•MI required troponin elevation & clinical event
Randomized trial in 7,000 high-risk patients•70% nitrous oxide•70% nitrogen
Myles, Lancet, 2014
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POISE-2 Background
Surgery•Inflammatory response activates platelets•Promotes tachycardia
Aspirin•Impairs platelet aggregation•Prevents non-operative primary & secondary MI
Clonidine•Moderates central sympathetic activation•Heart rate control•Less hypotension than beta blockers•Analgesic Devereaux, NEJM (2 papers) 2014
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POISE-2 Design
Inpatients >45 years at cardiovascular risk
Blinded 2 X 2 factorial trial•Aspirin 100 mg/day vs. placebo for 7 or 30 days•Clonidine 75 µg/day vs. placebo for 72 hours
Primary outcome•Death or MI within 30 days•MI required troponin elevation and clinical events
Safety outcomes•Life-threatening bleeding (i.e., required reoperation) •Clinically important hypotension (syst < 90 mmHg & Rx)•Clinically important bradycardia (HR <55/min & Rx)
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10,000 Randomized Patients
99.9% complete follow-up
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Patient Characteristics, Aspirin
Aspirin(N=4998)
Placebo(N=5012)
Age – (years) 69 69
Male (%) 52 53
Known vascular disease (%)
33 33
History of PCI (%) 4.7 4.7
Similar for clonidine
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Aspirin, Death & MI
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POISE-2 Results, AspirinOutcome Aspirin
(4998)Placebo(5012)
HR (95% CI)
P
1O outcome:death or nonfatal MI
351 (7.0) 355 (7.1) 0.99 (0.86-1.15)
0.92
Major bleed 229 (4.6) 187 (3.7) 1.23 (1.01-1.49)
0.04
Stroke 16 (0.3) 19 (0.4) 0.84 (0.43-1.64)
0.62
No interaction with clonidine
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POISE-2 Results, Clonidine
%
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POISE-2, Clonidine Results
Outcome Clonidine(5009)
Placebo(5001)
HR (95% CI)
P
Clinically important hypotension
2385 (48) 1854 (37) 1.32 (1.24-1.40)
<0.001
Clinically important bradycardia
600 (12) 403 (8) 1.49 (1.32-1.69)
<0.001
Stroke 18 (0.4) 17 (0.3) 1.06 (0.54-2.05)
0.87
No interaction with aspirin
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POISE-2 Conclusions
Aspirin•Does not prevent death or MI•Increases life-threatening bleeding•Should not be used for MI prophylaxis
Clonidine•Does not prevent death or MI•Causes clinically important hypotension•Should not be used for MI prophylaxis
A safe and effective way to prevent perioperative myocardial infarctions remains unknown
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Association with MAP
Mascha, Anesthesiology, in press
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Rare Outcomes: AKI and MI
Walsh, 2013
MAP < 55 mmHg
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SIRS Background & DesignBackground•In-hospital mortality after cardiac surgery ≈5%•Inflammation believed to contribute•Small studies suggest that steroids help
Patients•7,500, high-risk cardiac surgery (Euroscore ≥6)•Surgery with bypass
Intervention•500 mg methylprednisilone vs. placebo, N=7,500
Major outcomes•30-day mortality•Myocardial infarction•Atrial fibrillation Whitlock, in review
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SIRS ResultsOutcomes Steroid
N=3755PlaceboN=3752
RR (95% CI) p-value
First Co-Primary: Death
155 (4.1) 176 (4.7)0.88 (0.71-
1.09)0.23
Second Co-Primary: Composite death, MI, stroke, AKI, respiratory failure
908 (24) 869 (23)1.04 (0.96-
1.13)0.30
New atrial fib (%) 821 (21.9) 846 (22.5)0.97 (0.89-
1.06)0.53
MI 500 (13.3) 408 (10.9) 1.22 (1.08-
1.38) 0.001
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SIRS Conclusions
Methylprednisolone in high-risk cardiac surgery•Does not reduce death•Does not reduce composite major morbidity
Does not reduce atrial fibrillation
Steroids increase perioperative MI by 20%
Do not use prophylactic methylprednisolone
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Summary
MI after non-cardiac surgery•Common, mostly silent, and deadly
No known safe prophylaxis•Beta blockers work, but cause strokes•Nitrous oxide has no effect•Aspirin: no benefit and increased bleeding•Clonidine: no benefit and hypotension
Consider keeping MAP >55 mmHg
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Department of OUTCOMES RESEARCH