Medical Management and Risk
Factor Modification
SVS clinical research priorities
meeting 2011
Peter Henke, MD
University of Michigan
Overview
• Epidemiology of atherosclerotic/atherothrombotic manifestations in vascular
surgical patients
• Current medical management of arterial
vascular disease patients
– Evidence for major therapies
• Preoperative risk assessment pathways
• Current and potential study areas/questions
Background Issues
• Goals of medical management and risk factor
modification for the vascular surgeon
– Clinic setting and peri-operative setting
• Local practice patterns often dictate the vascular
medicine interest
– Do it all yourself to consult specialists for everything
• Costs saved for preventative care by vascular
surgeons
• Costs incurred due to multiple consultants and
elaborate workups with no discernable patient
benefit
Epidemiology
• All our patients
have
atherosclerosis
Lloyd-Jones D, etal
Circulation
2010;121:e1
Epidemiology
REACH Registry
N = 64,977 with CAD, CVOD, PAD or >3 risk factors
Steg PG, etal. JAMA
2007;297:1197
Epidemiology
REACH Registry
N = 68,236 with CAD, CVOD, PAD
Focus on AAA patients comorbidities
Baumgartner I, etal. J Vasc Surg 2008;48:808
Epidemiology
Baumgartner I, etal. J Vasc Surg 2008;48:808
Epidemiology
REACH Registry
N = 45,227 patients with CAD, CVOD, PAD or > 3 risks
4 yr outcome
Sig increased risk with DM (OR = 1.44); prior event (1.71); polyvasc Dz (1.99)
Bhatt, D, etal. JAMA 2010;304:1350
Atherothrombotic Costs
It’s expensive!
AHA statistics
2010
Heidenreich PA, etal. Circ
2011;123:933
Strong Evidence exists for Treating our
Patients
• Anti-platelet therapy (ASA, IA)
• Lipid mngt (LDL<100 mg/dL, IB)
• HTN control (BP < 140/90 or 130/80, IB)
– RAAS (IA) and B-blockers (IA)
• Smoking cessation (IB)
• Fitness and weight mngt (IB)
Smith SC, etal. Circulation
2006;113:2363
Medications: ASA
Meta-analysis of
ASA for primary
prevention
N = 95,000
12% reduction in
serious vascular
events
ATT collaboration. Lancet
2009;373:1849
Medications: ASA
Metaanalysis of 50,279 patients with
CAD for risk of events with DC
Biondi-Zoccai GL, etal. Eur Heart J 2006;27:2667
Medications: B-blockers
N= ~ 663,000
Propensity matched cohort from 329 US hospitals
Major non cardiac surgery
Adjusted Odds Ratio of In-hospital Mortality Associated with Beta Blocker
Therapy in Major Noncardiac Surgery Stratified by Revised Cardiac Index
(RCRI) Score
Lindenaeur PK, et al. N Engl J Med 2005;353:349-61
Medications: B-blockers
Bauer SM, etal. J Vasc Surg 2010;51:242
Medications: B-blockers
Percentage of Patients
N = 112
High risk vasc surgery
Bisoprolol 7-89 days pre-op (mean 37)
40
Standard care
30
D(%) MI(%)
CONT 17
BIS
3.4
20
P<0.001
17 0.02
0 <0.001
10
Bisoprolol
0
0
7
14
21
Days after Surgery
p
28
Poldermans D et al. NEJM 1999;341:1789
Medications: Statins
Bauer SM, etal. J Vasc Surg 2010;51:242
Medications: Statins
N = 497 RCT, mean
duration of use 37d
MI, Trop T was
primary composite
outcome
Decreased CRP, IL-6
All on b-blocker
Schauten O, etal. NEJM 2009;361:10
Medications: Statins
Schauten O, etal. NEJM 2009;361:10
Medications: Statins
Metaanalysis of ~800,000 pts for
perioperative risk reduction effects
Kapoor AS, etal. BMJ doi:10.1136
How well
do we do?
Rehring TF, etal. J Vasc Surg
2005;41:816
Database study of 2839 patients with PAD
Reviewed by ICD-9 codes, pharmacy, and labs
How well do we
do?
N = 325 vascular
surgical patients
Marchall C, etal. Vasc
Endovasc Surg 2009;43:238
How well do we do?
NHANES 19992004
ABI < .9
Risk adjusted rates of mortality
with multiple preventative
therapy: HR= .35; 95% CI .2-.86
Prande RL, etal. Circ 2011;124:17.
Post Op MI
Landesberg G, etal. Circulation 2009;119:2936
Post Op MI
Landesberg G, etal. Circulation 2009;119:2936
Well established guidelines
But are they actually followed?
Preoperative Evaluation
• Accepted and
noncontroversial
indications for
full cardiac
w/u prior to
surgery
Fleisher LA, etal.
Circulation 2007;116:1971
Preop risk tools
• RCRI
Lee TH, etal. Circulation 1999;100:1043
Preoperative Evaluation
• Derived from VSGNE (N = 10,081)
• Validated
• More sensitive in vascular surgical patients
than RCRI
Bertges DJ, etal. JVS 2010;52:674
Preop Risk: Biomarkers
N = 2054 elective
vascular surgery
pts
PMCE = MI, pul.
edema, death
RCRI improved
~ 20% on BB or
statin
Choi JH, etal. Heart 2010;96:56
Preop Risk: Biomarkers
N = 91 LEB patients
hsCRP, fibrinogen, SAA
FU ~ 1 yr
Owens CD, etal. JVS 2007;45:2
Preop Risk: Biomarkers
Metaanalysis of 3,281 pts with perioperative CV
complications
Karthikeyan G, etal. JACC 2009;54:1599
Preop Evaluation
Bauer SM, etal. J Vasc Surg 2010;51:242
Preop Stress testing
Meta-analysis of 68 studies with N = 10,049
LR = 8.35; 5.6-12.5 of po MI if positive
Beattie WS, etal. Anesth Analg 2006;102:8
Does preoperative stress testing help?
N = 99
RCT of preop stress test vs. none
after AHA guideline stratification
Falcone RA, etal. J Cardio Vasc Anesth 2003;17:694
No difference at one
year; 1 % CV
morbidity/mortality
Preop Evaluation:
Costs
Glance LG, etal. J Card Vasc Anesth 1999;23:265
Individual Costs of Preop Work Up
1.EKG = $135 ($75)
2.ECHO = $695 ($325)
3.Stress ECHO = $1708 ($644)
4.Nuclear Stress test = $725
($282)
5.Catheterization = $3000 ($1013)
6.Consult = $267-453
Professional fees are in ( )
Preop Cardiac Revascularization
N = 510
RCT of high risk vascular pts
Excl: AS, EF < 20%, LM dz
McFalls E, etal. NEJM 2004;351:27
Preop Cardiac Revascularization
N = 101 RCT of
high risk pts with
++ stress test
2.8 yr FU
No major
differences in
endpoints
Schouten O, etal,
JACC 2009;103:897
Preop Cardiac Revascularization
Biccard BM , etal. Anesthesia 2009;64:1105
What probably doesn’t need study
• Individual comparison of antiplatelet, statin, bblocker, and ACEI therapy in vascular disease
patient outcomes
– Evidence very strong from large CV trials, Registries,
Guidelines
• Preoperative cardiac revascularization in vascular
surgical patients
– Done twice; very intensive trials
• Antiplatelet therapy types for primary/secondary
prevention
Current Relevant Trials
www.clinicaltrials.gov
• Predictors of po outcome in PV surgical patients
• NCT01417910
• Cardiopulmonary exercise testing and
preoperative risk stratification
• NCT00737828
• Prospective study to assess screening value of NTproBNP for the identification of pts that benefit
from additional cardiac testing prior to vascular
surgery
• NCT00519961
• POISE-2 (ASA and clonidine)
• NCT00144937
Current Relevant Trials
• Multifactoral Intervention on CV risk factors in
subjects with PAD
• NCT00144937
• Multifactoral risk reduction for optimal
management of PAD
• NCT00537225
• Vascular events in noncardiac surgery patients
cohort evaluation
• NCT00512109
Potential Topics to Study
• Preoperative cardiac risk stratification comparative
study
– Risk equation and added biomarkers to increase pretest
probability
– Preoperative stress testing usefulness
• Postoperative MI care – heterogeneous
– Large multicenter survey / Study best practices
• Intensive vs. usual cardiovascular medical care in high
risk arterial disease patients
– GWtG/GAP paradigm for following AMI pathway
– Active pathway intervention vs. simple recommendation
reminders
– Steno II paradigm of multimodal intensive therapy for DM
GWtG
Lewis WR, etal. Arch Int
Med 2006;168:1813
GAP
Eagle KA, etal. JACC 2005;46:1242
GAP
Eagle KA, etal. JACC 2005;46:1242
Steno-2 Model
• N = 160
• RCT of intensive
multimodality
therapy vs. usual
care
• F/U ~ 8 yrs
• Composite
endpoint of death,
CV morbidity,
amputation
Gaede P, etal. NEJM
2003;348:383
Steno-2
Model
Gaede P, etal. NEJM
2003;348:383