Coronary Stent Choice in Patients With Diabetes Mellitus

Rome Cardiology Forum 2014

Stephan Windecker

Department of Cardiology

Swiss Cardiovascular Center and Clinical Trials Unit Bern

Bern University Hospital, Switzerland

Scientific Advances and Cardiovascular Mortality

Nabel and Braunwald. N Engl J Med 2012;366:54-63

2002 Efficacy of

drug-eluting vs. bare-

metal stents determined

Drug-Eluting Stents

Stefanini G, Holmes D. N Engl J Med 2013; 368:254-65

Progress in Metallic DES Technology Stefanini, Taniwaki, Windecker. Heart 2013, online ahead of print

Coronary Stent Choice

Vascular Biology

Efficacy

Safety

Diabetes Mellitus

Cook et al. Circulation 2007

Guagliumi et al. Circulation 2011

Cook et al. Circulation 2009

Inflammation and Vessel Remodeling

P=0.0003

P<0.0001

Nakazawa et al. J Am Coll Card 2011

Neoatherosclerosis

P<0.0001

Pathological Healing Response to Implantation of Early Generation DES

Uncovered Struts

Coronary Evaginations

Räber et al. J Am Coll Card Intv 2012

Human Pathology of New Generation EES Compared With Early Generation SES and PES

Otsuka F et al. Circulation 2014; 129:211-223.

SES PES EES

>30% Uncovered Struts

Arterial Healing After Coronary Stents Implantation Stefanini G, Holmes D. N Eng J Med 2013;368:254-65

BMS Early DES New DES

Coronary Stent Choice

Vascular Biology

Efficacy

Safety

Diabetes Mellitus

Mortality and Repeat Revascularization with Early Generation DES versus Bare Metal Stents

Mortality Repeat Revasc

1 0·2 2 5 0·5

SES vs BMS

PES vs BMS

SES vs PES

1.00 (0.82-1.25)

1.03 (0.84-1.22)

0.96 (0.83-1.24)

1 0·2 2 5 0·5

SES vs BMS

PES vs BMS

SES vs PES

0.30 (0.24-0.37)

0.42 (0.33-0.53)

0.70 (0.56-0.84)

HR (95% CI)

0

10

20

30

40

50

SES vs BMS PES vs BMS SES vs PES

NNT=7 (CI 6-8)

NN

T

NNT=8 (CI 7-10)

NNT=35 (CI 23-65)

HR (95% CI)

Stettler C et al. Lancet 2007;370:937-48

Everolimus-Eluting Stents

vs. Sirolimus-Eluting Stents

Biodegradable Polymer DES

vs. Sirolimus-Eluting Stents

Target Lesion Revascularization

Stefanini, Windecker Stefanini G et al. Eur Heart J 2012; 33, 1214–1222

Favors BP DES Favors SES Favors EES Favors SES

N = 11,167 – Updated Metaanalysis N = 4,062 – IPD Pooled Analysis

New Generation DES Improved Efficacy

18.6%

7.8%

6.3%

Overall

P<0.001

Early vs. Newer DES

P=0.005

Target Lesion Revascularization

11,557 Women enrolled into 26 Randomized Trials between 2000 and 2013

Safety and Efficacy of DES vs BMS Stefanini G et al. Lancet 2013; 382(9908):1879-88

Coronary Stent Choice

Vascular Biology

Efficacy

Safety

Diabetes Mellitus

Early DES and Very Late ST

Bavry A et al. Lancet 2008

SIRTAX LATE Räber L et al. Circulation 2011

1.3%

2.1%

1.1%

Overall

P=0.01

Early vs. Newer DES

P=0.002

Definite/Probable Stent Thrombosis

11,557 Women enrolled into 26 Randomized Trials between 2000 and 2013

Safety and Efficacy of DES vs BMS in Women Stefanini G et al. Lancet 2013; 382(9908):1879-88

Stent Thrombosis With Everolimus-Eluting Stents and Bare Metal Stents

A Network Meta-Analysis Palmerini T et al. Lancet 2012; 379:1393-402

DES vs. BMS in Large Coronary Arteries Kaiser C et al. N Eng J Med 2010; 363:2310-9

2.6

3.2

4.8

HR 0.60 (0.39-0.93)

P=0.022

Courtesy: C Kaiser for the BASKET-PROVE Investigators

Overall

Large Investigator-Driven Trial: BASKET-PROVE

EES vs. SES vs. BMS DES Pooled vs. BMS

Death or Myocardial Infarction

12.8%

10.9%

9.2%

Overall

P=0.001

Early vs. Newer DES

P=0.01

11,557 Women enrolled into 26 Randomized Trials between 2000 and 2013

Safety and Efficacy of DES vs BMS in Women Stefanini G et al. Lancet 2013

Coronary Stent Choice

Vascular Biology

Efficacy

Safety

Diabetes Mellitus

Median SYNTAX-Score = 26

13.0%

11.9%

26.6%

18.7%

Strategies for Multivessel Revascularization in Patients with Diabetes – the FREEDOM Trial

Farkouh ME et al. N Engl J Med 2012; 367:2375-84.

Death, MI, or Stroke Through 5 Years

FREEDOM TRIAL

Farkouh ME et al.

N Engl J Med 2012

32,966 patients

assessed

1,900 patients

randomized

= 5.6%

Anticipated difference

in outcome between

PCI and CABG

- RR 23%

146 patients lost to

follow-up/withdrew

= 4.4%

Generalisability?

92 32

FREEDOM TRIAL – PATIENT FLOW Farkouh ME et al. N Engl J Med 2012; 367:2375-84

FREEDOM TRIAL – MORTALITY Farkouh ME et al. N Engl J Med 2012; 367:2375-84

N=118

N=86

Sensitivity Analysis - Mortality

All non-evaluable

patients

having survived

All non-evaluable

patients

having died

PCI 118 177

CABG 86 173

FREEDOM TRIAL – STROKE OVER TIME Farkouh ME et al. N Engl J Med 2012; 367:2375-84

CABG VS PCI – RISK OF STROKE Palmerini T et al. J Am Coll Cardiol 2012

Adverse Cerebral Outcomes After

Coronary Artery Bypass Surgery Roach et al. N Engl J Med 1996;335:1857-63

0,1

1,9 1,8 2,2

5,5

8

0,1

1,2 1,7

2,2

4,5

9

0

2

4

6

8

10

<40 40-49 50-59 60-69 70-79 >80

Type I (Overall: 3.1%)

Type II (Overall: 3.0%)

(years)

Type I neurologic deficit: stroke, TIA, coma

Type II neurologic deficit: deterioration of intellect or seizures

21

10

2

0

10

20

30 Type I

Type II

No cerebral adverse event

In-hospital Mortality

%

Adverse Cerebral Outcomes After Coronary Artery Bypass Surgery

Roach et al. N Engl J Med 1996;335:1857-63

%

32

60

90

0

20

40

60

80

100 Type I

Type II

No cerebral adverse event

Discharge to Home

Target Lesion Revascularization Network Meta-Analysis: DES vs BMS

Stettler C et al. BMJ 2008; 337:a1331

Diabetic Patients

N=3,852

Non-Diabetic Patients

N=10,947

Mortality in Diabetic vs Non-Diabetic Patients in Trials With At Least 6 Months Clopidogrel

Stettler C et al. BMJ 2008; 337:1331

Diabetic Patients

N=3,852

Non-Diabetic Patients

N=10,947

Everolimus- Versus Paclitaxel-Eluting Stents Among Diabetic and Nondiabetic Patients

Stone G et al. Circulation 2011; 124:893-900

MACE @ 2 Years

IPD of SPIRIT II, III, IV, and COMPARE Trials (N=6,789)

P-inter = 0.0009

Death or MI in Major Subgroups

Early DES vs. BMS New DES vs. BMS

Drug-Eluting vs. Bare-Metal Stents in Women Stefanini G et al. Lancet 2013; 382(9908):1879-88

11,557 Women enrolled into 26 Randomized Trials between 2000 and 2013

DIFFUSE MULTIVESSEL CAD

Jolicoeur EM et al. Can J Cardiol 2012

Coronary Scaffolds Compared With Coronary Stents

Stents

Scaffolds

Caged Vessel Scaffolding function

and drug release

Scaffolding function

and drug release

Bioresorption Restoration of

vascular physiology

and lumen

enlargement

Efficacy and Safety of DES, BMS, and CABG According to Clinical Indication

Stefanini G, Holmes D. N Eng J Med 2013;368:254-65

Conclusions

• Advanced stent platforms with excellent

deliverability, less arterial injury and

improved biocompatibility

• The risk of repeat revascularization is further

reduced

• The risk of ST is extremely low

• Diabetes remains the Achilles heel of

current DES, particularly in patients with

complex multivessel disease