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

Medications: B-blockers

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

Medications: B-blockers

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

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

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

Medications: Statins

Schauten O, etal. NEJM 2009;361:10

Medications: Statins

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

Preop Risk: Biomarkers

Owens CD, etal. JVS 2007;45:2

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

Preop Risk: Biomarkers

Karthikeyan G, etal. JACC 2009;54:1599

Metaanalysis of 3,281 pts with perioperative CV complications

Preop Evaluation

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

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

Preop Cardiac Revascularization

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

Preop Cardiac Revascularization

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