Medical Management and Risk Factor Modification SVS clinical research priorities meeting 2011 Peter Henke, MD University of Michigan.

Medical Management and Risk Factor Modification

SVS clinical research priorities meeting 2011

Peter Henke, MDUniversity 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

Lloyd-Jones D, etal Circulation 2010;121:e1

• All our patients have atherosclerosis

Epidemiology

Steg PG, etal. JAMA 2007;297:1197

REACH RegistryN = 64,977 with CAD, CVOD, PAD or >3 risk factors

Epidemiology

Baumgartner I, etal. J Vasc Surg 2008;48:808

REACH RegistryN = 68,236 with CAD, CVOD, PADFocus on AAA patients comorbidities

Epidemiology

Baumgartner I, etal. J Vasc Surg 2008;48:808

Epidemiology

Bhatt, D, etal. JAMA 2010;304:1350

REACH RegistryN = 45,227 patients with CAD, CVOD, PAD or > 3 risks4 yr outcomeSig increased risk with DM (OR = 1.44); prior event (1.71); polyvasc Dz (1.99)

Atherothrombotic Costs

AHA statistics 2010

Heidenreich PA, etal. Circ 2011;123:933

It’s expensive!

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 preventionN = 95,000

12% reduction in serious vascular events

ATT collaboration. Lancet 2009;373:1849

Medications: ASA

Biondi-Zoccai GL, etal. Eur Heart J 2006;27:2667

Metaanalysis of 50,279 patients with CAD for risk of events with DC

Medications: B-blockers

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

N= ~ 663,000Propensity matched cohort from 329 US hospitalsMajor non cardiac surgery


Bauer SM, etal. J Vasc Surg 2010;51:242


P<0.001

0 7 14 21 28Days after Surgery

Per

cen

tag

e o

f P

atie

nts

0

10

20

30

40

Standard care

Bisoprolol

N = 112High risk vasc surgeryBisoprolol 7-89 days pre-op (mean 37)

D(%) MI(%) p

CONT 17 17 0.02BIS 3.4 0<0.001

Poldermans D et al. NEJM 1999;341:1789

Medications: Statins



Schauten O, etal. NEJM 2009;361:10

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


Kapoor AS, etal. BMJ doi:10.1136

Metaanalysis of ~800,000 pts for perioperative risk reduction effects

How well do we do?

Database study of 2839 patients with PADReviewed by ICD-9 codes, pharmacy, and labs

Rehring TF, etal. J Vasc Surg 2005;41:816

How well do we do?

Marchall C, etal. Vasc Endovasc Surg 2009;43:238

N = 325 vascular surgical patients

How well do we do?

Prande RL, etal. Circ 2011;124:17.

Risk adjusted rates of mortality with multiple preventative therapy: HR= .35; 95% CI .2-.86

NHANES 1999-2004ABI < .9

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 non-controversial 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

Choi JH, etal. Heart 2010;96:56

N = 2054 elective vascular surgery ptsPMCE = MI, pul. edema, deathRCRI improved

~ 20% on BB or statin


Owens CD, etal. JVS 2007;45:2

N = 91 LEB patientshsCRP, fibrinogen, SAAFU ~ 1 yr


Karthikeyan G, etal. JACC 2009;54:1599

Metaanalysis of 3,281 pts with perioperative CV complications

Preop Evaluation


Preop Stress testingMeta-analysis of 68 studies with N = 10,049LR = 8.35; 5.6-12.5 of po MI if positive

Beattie WS, etal. Anesth Analg 2006;102:8

Does preoperative stress testing help?

Falcone RA, etal. J Cardio Vasc Anesth 2003;17:694

N = 99RCT of preop stress test vs. none after AHA guideline stratification

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

McFalls E, etal. NEJM 2004;351:27

N = 510RCT of high risk vascular ptsExcl: AS, EF < 20%, LM dz


Schouten O, etal, JACC 2009;103:897

N = 101 RCT of high risk pts with

++ stress test

2.8 yr FU

No major differences in endpoints


Biccard BM , etal. Anesthesia 2009;64:1105

What probably doesn’t need study• Individual comparison of antiplatelet, statin, b-

blocker, 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 Trialswww.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 NT-proBNP 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

Medical Management and Risk Factor Modification SVS clinical research priorities meeting 2011 Peter Henke, MD University of Michigan.

Documents