Invasiv behandling af hjertepatienten med diabetes

AstraZenecas 32. kardiovaskulære årsmøde

Kolding 23.-24. januar 2009

Hans Erik Bøtker

Is outcome of percutaneous coronary intervention(PCI) inferior to bypass surgery (CABG) in

diabetic compared to non-diabetics patients ?

A persistent controversy!!GuidelinesESC 2007 – DCS 2008

PCI in diabetic patients

has been improved during the last 3 - 4 years- so has CABG

Nielsen & Bøtker. Horm Metab Res 2005;37 Suppl.,83-89

PTCA vs. CABG in DM:randomized studies

0

10

20

30

40

50

EAST1994

BARI1996

CABRI1995

ERACI1993

Overall

PCI

CABG

Mor

talit

y (%

)

8 yr 7 yr 4 yr 1 yr

p=0.23

P<0.003

NS

NS

PCI vs. CABG in DM:Registry studies

0

10

20

30

40

50E

mory

LD

CM

C

Duke

MA

HI

BA

RI-

R

NN

E

AP

PR

O

Overa

ll

PCI

CABG

Mor

talit

y (%

)

By pass surgery versus PCIBy pass surgery versus PCI

The BARI randomized trial comparing CABG and PTCAPatients with diabetes (and more unfavourable baseline characteristics that patients without diabetes) (n=353)

The Bari Investigators Circulation 1997; 96:1761

25

15

10

5

0CABGLIMA

CABGSVG

PTCA

Adjusted RR7.4 8.1

Five year mortality by type of intervention

Mo

rta

lity

(%)

By pass surgery versus PCI (BMS)By pass surgery versus PCI (BMS)

Stenting vs. CABG in multivessel disease. Subgroup analysis from ARTSMultivessel disease n = 1.205 Diabetes n = 208 (17%)

CABGCABG

Stented PCI

Stented PCI

100

90

80

70

60

50 Eve

ntfr

ee

su

rviv

al (

%)

Diabetes

NoYes

No

Yes0 240 480 720 960 1200 Follow up (days)

Three year survival free from stroke, MI and revascularization

Legrand et al Circulation 2004;109:1114-20

PCI with BMS vs. CABG

0

10

20

30

40

50D

eath

Repat

RV

Death

Repeat

RV

PCI

CABG

(%)

-DM +DM

P<0.01

De

ath

,MI,

stro

ke

De

ath

,MI,

stro

keLegrand et al. ARTS 3-year FUP. Circulation 2004; 109: 1114-20

P<0.01

NS

NS

NS

NS

P<0.04

Syntax: DES vs. CABG MACCE to 12 Months all patients

P=0.0015*

0 6 12

10

20

0

Months Since Allocation

Cu

mu

lati

ve E

ven

t R

ate

(%

)(d

eath

+C

VA

+M

I+re

peat

rev

asc.

)

ITT population

12.1%

17.8%

Event Rate ± 1.5 SE. *Fisher’s Exact Test

TAXUS (N=903)CABG (N=897)

Syntax: DES vs. CABG MACCE to 12 Months all patients

Syntax: Outcome according to Diabetic Status (subgroup )

Diabetes (Medical Treatment)N=452

Non-DiabeticN=1.348

TAXUS

CABG

Death/CVA/MI MACCE Death/CVA/MI MACCE

P=0.96 P=0.0025P=0.08P=0.97

Death/CVA/MI MACCE

Cardia trial: endpoints

Cardia• Styrker

• Stor (n=510), randomiseret, sammenlignende, nordeuropæisk interventionsundersøgelse på diabetes patienter

• Minimal cross over

• Svagheder

• 1 års follow up• Screenings log uoplyst• Stop for inklusion af nødvendige

antal patt. Iht. styrkeberegning → underpowered mhp. at afkræfte non-inferiority

• Mange små centre (14 af 24 centre randomiserede < 3 ptt./år)

• Få DES (drug eluting stents) (71%)

• Få LIMA grafter (89%)• LM stenoser ekslusionskriterium• Højere forekomst af hyperlipidæmi

i PCI armen (93 vs 87%)• Flere 3-kar-syge i PCI armen (65

vs 58%)

CABG/PCI anbefaling

• Treatment decisions regarding revascularization in patients with diabetes should favour coronary artery bypass surgery over percutaneous intervention IIa, A.

Revaskularisering vha. CABG eller PCI beror på individuel vurdering (koronaranatomi,

operationsrisici m.m.)

Individual treatmentThere is ‘3 Vessel Disease’ and ‘3 Vessel Disease’

Influence of Syntax score

PCI vs. CABG in surgical risk patients

• AWESOME ptt.s

• Prior CABG• AMI < 7 days• EF < 0.35• Age > 70 years• IABP to stabilize

• Total / DM

• 2,431 / 758 (31%)• Randomized: 454/144

(32%)• Physician directed registry:

1650/525 (32%)• Patient directed registry:

327/89 (27%)

AWESOME, JACC, 2002; 40:1555-66

PCI in surgical risk patients with DM

AWESOME, JACC, 2002; 40:1555-66

Randomized

Register: Patient-choice

Register: Physician-directed

Survival

Outcome by individual evaluation

Tarantini et al.Catheter Cardiovasc Interv 2009;73:50–58

A clinical judgment-basedrevascularization by DES-PCI is not associated with worse 2-year outcome comparedwith CABG.

(n=93)

(n=127)

Modern PCI

• Drug eluting stents

• Optimal anti-thrombotic and other medication

Bare metal vs. drug eluting stentsBare metal vs. drug eluting stents

Sabaté et al. Circulation 2005; 112:2175

RCT in patients with diabetesSirolimus (n = 80; 111 lesions) Bare metal (n = 80; 110 lesions)

End-point: in segment late lumen loss by QCA after 9 months

Late lumen loss0.06±0.4 mm

Late lumen loss0.47 ±0.5

Variable DES BMSVariable DES BMS %% % %

Target lesion revascTarget lesion revasc 7.37.3 31.331.3

Major CV eventMajor CV event 11.311.3 36.336.3

p<0.001p<0.001

Differences between DES?

Billinger, M. et al. Eur Heart J 2008 29:718-725

Clinical outcome for three trial directly comparing SES and PES: ISAR-DIABETES, REALITY, SIRTAX

Major adverse cardiac events

Target lesion revascularization

Billinger, M. et al. Eur Heart J 2008 29:718-725

DES Penetration in Scandinavia

Something is rotten in the state of Denmark?

DK

S

Definite Stent Thrombosis at 12-15 months after index PCI

DES 0.09%BMS 0.009%

Adjusted RR = 10.9 (1.27 to 93.76)

p=0.029

Jensen LO et al. J Am Coll Cardiol 2007;50:463-70.

DES and stent thrombosis in DM

Spaulding et al. NEJM 2007;356:989-97

- DM + DM

Combined Definite, Probable or Possible Stent Thrombosis in DM

Adjusted RR=0.70 (0.33-1.48)

ns

Maeng et al. Am J Cardiol 2008;102:165-72.

DES long term effect in DM

Stettler et al. BMJ 2008; 337:a1331

>6 mo clopidogrel treatment

DES

• When PCI with stent implantation is performed in a diabetic patient, drug eluting stents should be used - IIa, B

• Ved PCI anbefales brug af medicinafgivende stents efterfulgt af 12 måneders behandling med 75 mg clopidogrel

1 Year Mortality in Diabetics by PCI Strategy With and Without Abciximab

EPIC, EPILOG, and EPISTENT Meta-AnalysisEPIC, EPILOG, and EPISTENT Meta-Analysis

5.0 4.6

7.7

2.9

1.30.9

0

2

4

6

8

10

PTCA Stent Multi-Vessel PCI

JACC 2000; 35:922-28

p = 0.110 2.1%

p = 0.042 3.3%

n=614n=343 n=230n=197

% o

f P

atie

nts

p = 0.018 6.8%

n=108n=65

Placebo Abciximab

ISAR SWEET

ISAR SWEET: pretreatment with clopidogrel 600 mg

DM: indication for intensive anti-thrombotic therapy during PCI?

• Bivalirudin: REPLACE-2, ACUITY, HORIZONS

• TRITON-TIMI-38: Prasugrel

Antithrombotic treatment

• Glycoprotein IIb/III inhibitors are indicated in elective PCI in patients with diabetes I, B.

• Brug af glycoprotein IIb/IIIa-hæmmere anbefales i forbindelse med PCI proceduren

Revascularization of patients with DM

Patients with DM can (probably) be revascularized as patients without DM

• CABG with LIMA in 3-vessel disease and lesions not suitable of PCI

• PCI in 1- and 2-vessel disease without need of LIMA• PCI first choice in surgical high risk patients with multivessel disease when possible

Unresolved issues

Incomplete revascularization New lesions Co-morbidity Metabolic dysregulation

Glucometabolic dysfunction

Corpus et al. J Am Coll Cardiol 2004; 43: 8-14

Unresolved issuesUnresolved issues

Important ongoing trials

FREEDOM Diabetes mellitus type 2 Randomised to CABG or PCI (+DES) Death, MI or repeat revascularization Follow up 5 years

BARI IID Diabetes mellitus type 2 Early revascularization or optimal medical therapy Glucose lowering randomised Follow up 6 years