Management of cardiovascular disease

- coronary interventions -

Francesco Cosentino MD, PhD, FESC

Division of Cardiology

2nd Faculty of Medicine

University "Sapienza"

Rome, Italy

Master Classes in Preventive Cardiology I

Management of diabetes in patients with CVD

European Heart House

Revascularisation: which is better PCI

or CABG?

Coronary interventions

Patients with diabetes have:

– higher complication rate

– higher long-term mortality/morbidity following revascularization both after bypass surgery and PCI, even in the era of DES

– greater incidence of 3-vessel, more diffuse disease in proximal and distal segments (NHLBI PCI registry)

– Most outcome information is derived from registries and sub-group analyses (selection bias)

NEJM 1996; 335: 217

Comparison of CABG with PTCA in pts with CAD

Bypass Angioplasty Revascularisation Investigation (BARI)

Survival advantage in the

CABG compared to the

PCI cohort1289 pts with multivessel disease

of whom 353 had diabetes.

BARI Trial 10-Year Follow-Up Results

BARI Investigators, JACC 2007

Hlatky MA et al, Lancet 2009

• 1223 diabetic patients enrolled

in 10 PCI vs CABG trials

(6 PTCA and 4 BMS)

• median FU 5.9 years

• Long-term survival benefit

of CABG among 1223

diabetic patients

• Interaction between diabetes

status and treatment effect

2009 Collaborative meta-analysis of 10 RCT

PCI vs. CABG in multivessel CAD

Mo

rta

lity

%

PCI diabetes

CABG diabetes

PCI/CABG no diabetes

Years of follow-up

undertaken

Arterial Revascularization Therapy StudyA subgroup analysis of the ARTS-I trial

Abizaid et al Circulation 2001

BMS vs CABG in pts with multivessel CAD

Has the use of DES in diabetic patients

changed results first seen in

the pre-DES trials favouring CABG?

ARTS II TrialSES-PCI in Diabetes with multivessel CAD

(single-arm study)

3-year clinical outcomes for ARTS-I and -II diabetic patients

Daemen et al. JACC 2008

ARTS-I: PCI with BMS vs CABG

ARTS-II: PCI with SES

Incidence of MACCE (efficacy) Death/CVA/AMI (safety)

Collaborative Network Meta-analysis All Cause Mortality

• 35 studies

• 10947 non-diabetic and 3852 diabetic patients

Stettler C et al. BMJ 2008;337:a1331

Collaborative Network Meta-analysis Target Lesion Revascularization

DES seem same and effective

Stettler C et al. BMJ 2008;337:a1331

• Both DES were associated with a decrease in revascularization rates compared

with BMS in pts with and w/out diabetes

Massachussets Registry – DM - 3-Years Mortality

• Analysis including all patients undergoing PCI in non-federal hospital in

Massachussets between April 2003 and September 2004

• 5051 DM patients

• Unadjusted 3-year mortality 14.4% DES group and 22.2 BMS group (P<0.001)*

Propensity matched diabetic cohorts

Garg P et al. Circulation 2008;118:2277-85

Massachussets Registry – DM – 3-Years TVR

Propensity matched diabetic cohortsGarg P et al. Circulation 2008;118:2277-85

Risk-adjusted 3-year revasc rate 18.4% DES group and 23.7 BMS group (P<0.001)

Synergy between PCI with Taxus and Cardiac Surgery

(SYNTAX Trial)

1800 pts with LM or triple vessel CAD

the primary outcome occured more often in the PCI group

Serruys et al. NEJM 2009;360:961-72

Coronary Artery Revascularization in Diabetes (CARDia)DM and triple-vessel CAD

p =0.63

10.5%

13.0%

N=510

Primary endpoint: death, non fatal MI,

non fatal stroke

Preliminary results at 1 year

p=0.04

11.3 %

19.3 %

N=510

Coronary Artery Revascularization in Diabetes (CARDia)Higher rate of repeat revasc in the PCI group

Revascularization or Medical Management?

• Unstable CAD

• Stable CAD

Better

0 0.5 1.5 2.5

Adjusted Odds Ratio & 95% CI

p < 0.0001

Worse

21

Total, N = 29570Diabetes, N = 6458

Diabetic pts with non-ST ACS have higher 30-day mortality

Roffi et al.,Circulation 2001;104 2767-71

Diabetes

meta-analysis of the diabetic populations within IIb-IIIa inhibitor trials

Early Invasive or Conservative

Strategy in UA and NSTEMI 6 Months

p = 0.232

p = 0.028

ejt 0303–129

N=613 N=1607

DiabetesDiabetes No DiabetesNo Diabetes00

55

1010

1515

2020

2525

3030

27.727.7

20.120.1

16.416.414.214.2

Conservative

Invasive

Death, MI, Rehosp ACS, (%)Death, MI, Rehosp ACS, (%)

RRR 27%

ARR 7.6%

RRR 13%

ARR 2.2%

P=NSP<0.05

Cannon et al. NEJM 2001;344:1879-87

ESC Guidelines for the Management of NSTE-ACS

ESC ACS Guidelines 2007

Recommendations for Diabetes

Early invasive strategy is recommended for diabetic patients with NSTE-ACS (I – A).

Impact of revascularization vs med therapy alone

on mortality in stable CAD

• 28 trials, published 1977-2007

• 13121 pts (~470 patients/trial)

• Median FU 3 years

• No diabetes data

Jeremias A et al. Am J Med 2009;122:152-61

Meta-Analysis of Randomized Trials

Soares, P. R. et al. Circulation 2006;114:I-420-I-424

N=190 Diabetics

• 611 patients with stable multivessel CAD

• Randomized 1995-2000 to PCI, CABG or medical Tx

• 190 diabetic patients

• 5 yrs follow up

Coronary revascularization decreases mortality in

diabetics with stable multivessel disease

A retrospective analysis of MASS II study

Impact of Revascularization: Euro-Heart Survey

No DM, Revasc

No DM, No Revasc

DM, Revasc

DM, No Revasc

Freedom from MACE

Anselmino et al. Eur J Cardiovasc Prev Rehabil 2008;15:216-23

Impact of EBM: Euro-Heart Survey

Anselmino et al. Eur J Cardiovasc Prev Rehabil 2008;15:216-23

DM, No EBM

No DM

DM, EBM

Freedom from MACE

QuickTime™ e undecompressore

sono necessari per visualizzare quest'immagine.

Stable CAD and DiabetesPCI, CABG or medical management?

confront treatment decisions in practice

BARI 2D: study design

• 2368 diabetic pts with T2DM and stable CAD

• 2x2 design

– revascularization (CABG or PCI) + intensive medical tx vs. intensive medical tx alone

– insulin sensitization (metformin/TZD) vs. insulin provision (sulfonylureas/insulin)

• Randomization to PCI or CABG prespecified by the physician as the more appropriatetherapy for each patient

The BARI 2D study group NEJM 2009

2 parallel strategies for

death and CVE

2 parallel strategies for

long term death and CVE

The BARI study group NEJM 2009

1º endpoint: death

2º: death/MI/stroke

Follow-up 5 yrs

BARI 2Dlittle difference with respect to rates of survival and MACE

Outcomes in the CABG Subgroup of BARI 2D Trialprespecified analyses of secondary end point

Sobel BE, Coron Artery Dis 2010

The BARI study group NEJM 2009

reduction of death/nonfatal MI/stroke only among pts

who were selected to undergo CABG. Ins sens

associated with fewer CVE.

BARI 2D: Patients Characteristics

Low risk population for major CVE

on the basis of angina

symptoms, extent of CAD and VF

Conclusions (I)

• Diabetic patients at higher risk of CV events with both PCI and CABG

• Improvements in techniques for both PCI and CABG

• DES-PCI and CABG

– At 1 year similar death/MI/stroke rates

– PCI → more revascularization

– CABG → more stroke

• Choice of revascularization strategy based on diffuseness of atherosclerosis, clinical presentation, type of diabetes, comorbidities, pattern of coronary involvement, LV function.

• Interventional (Syntax) and surgical scores (Euroscore) should be taken into account

• Threshold for surgery should be lower in diabetic patients than in non-diabetic counterparts (especially in IDDM)

• Longer FU of the presented trials and results of ongoing controlled randomized trials in pts with diabetes (CARDia, FREEDOM) will further help in decision making

Conclusions (II)

• Optimal medical management is crucial, independently of revascularization strategy

• Initial conservative strategy is a valuable option

→ In the presence of optimal compliance to medical management

→ in low-risk diabetic patients (stable symptoms, moderate CAD on coronary angiogram, normal LV and renal function)

• Results of BARI 2 D cannot be extrapolated

→ to unstable or in other respect higher risk diabetic patients

→ to diabetic patients with unknown coronary anatomy

Diabetes with CAD

a moving target against which the effectiveness of evolving treatments must be repeatedly assessed

ESC/EASD Guidelines 2007

• Mechanical reperfusion by means of primary PCI is the revascularization mode of choice in diabetic patients with AMI (I – A)

• When PCI with stent implantation is performed in patients with diabetes, DES should be used (IIa - B)

• Glycoprotein IIb/IIIa inhibitors are indicated in elective PCI in patients with diabetes (I - B)