Gu K et al. Diabetes Care 1998;21:1138 with Diabetes Mellitus. CAD Associated with Diabetes Mellitus. Hammond Diabetes and CHD Mortality. Diabetes …
Coronary Intervention and the Diabetic Patient
Charles J Davidson, MD Professor of Medicine Director, Interventional Cardiology Program Chief, Cardiac Catheterization Laboratories
Northwestern University Medical School
1
Mechanical Revascularization for Coronary Artery Disease in Diabetics Clinical Characteristics Prognosis After MI Balloon PCI Bare Metal Stent PCI Comparison with CABG DES impact on PCI outcomes
NRMI: Prevalence of Diabetes over Time
Trend p0001
40 35 30
255 262 267 276 289 297 303 310 308
N 410,223 208
25 20 15 10 5 0 1994 1995 1996 1997 1998 1999 2000 2001 2002
Mortality in Diabetics
Causes of Death
50 40
of Deaths
30 20 10 0
Ischemic heart disease Other Diabetes Heart Disease Cancer Stroke Infection Other
Geiss LS et al In: Diabetes in America 2nd ed 1995; chap 11
Mortality Due to Heart Disease in Men and Women with or without Diabetes
35 30
Mortality per 1000 person-years
299 230 192 115 63 71
Diabetes No Diabetes
25 20 15 10 5 0
110 36
Men
Women
Men
Women
All heart disease
Ischemic heart disease
Age-adjusted Adapted from Gu K et al Diabetes Care 1998;21:1138-1145
CAD Associated with Diabetes Mellitus
Angiographic Findings
Diffuse and
distal CAD Extensive disease with angiographically small reference vessels Multivessel disease Frequent left main disease Poorer coronary collateral vessel development Lower ejection fraction
Hammond et at JACC 200036;355-65
Key Issues in Diabetic Atherosclerosis
Increased thrombogenicity Increased thrombogenicity More frequent lipid-rich plaque More frequent lipid-rich plaque plaque rupture plaque rupture predisposed to predisposed to
Increased risk of restenosis after all forms of PCI Increased risk of restenosis after all forms of PCI
Increased risk of occlusive restenosis Increased risk of occlusive restenosis strong association with mortality strong association with mortality
Mechanical Revascularization for Coronary Artery Disease in Diabetics Clinical Characteristics Prognosis After MI Balloon PCI Bare Metal Stent PCI Comparison with CABG DES impact on PCI outcomes
Diabetes and CHD Mortality
Haffner et al N Engl J Med 1998 339;232
Diabetes and MI
Lee at al Circ 2004; 109:858
Diabetics with MI
No Prior MI 1460 Fatal CHD or Nonfatal MI n634 Event rate, per 1000 person-yrs RR Multivariate RR Cardiovascular Mortality n358 Death rate, per 1000 person-yrs RR Multivariate
RR 141 108 100 100 110 76 100 100 Prior MI 98 31 322 30 20-44 233 15-35 24 246 33 21-51 29 18-45 P value
0001 0001
002 0003
Lee et al Circ 2004; 109:858
Diabetics with MI
Mak et al JACC 1997 30;175
Diabetes and Revascularization
13
Revascularization in Diabetes:
The Problems
Co-morbidity PVD , CRF Peri-procedural complications Worse long-term clinical outcomes death , MI , stroke Excessive restenosis intimal hyperplasia negative remodeling Accelerated atherosclerosis progression of disease small vessel/diffuse disease
Mechanical Revascularization for Coronary Artery Disease in Diabetics Clinical Characteristics Prognosis After MI Balloon PCI Bare Metal Stent PCI Comparison with CABG DES impact on PCI outcomes
Balloon PCI in Diabetics MI Rate
Kip et al Circ 1996;94,1821
Balloon PCI in Diabetics Mortality Rate
Kip et al Circ 1996;94,1821
Mechanical Revascularization for Coronary Artery Disease in Diabetics Clinical Characteristics Prognosis After MI Balloon PCI Comparison with CABG Bare Metal Stent PCI DES impact on PCI outcomes
BARI Study Populations and Treatments
Eligible for Randomization Suitable for PTCA and CABG N4107 Consent to Randomization Randomized
Population N 1829 Randomly Assigned Treatment CABG N 914 PTCA N 915 Consent to Registry Follow-up Only ENR Registry Population N 2010 Treatment Received within 3 Months after Study Entry CABG N 625 PTCA N 1189 Medical/None N 196 Refused Randomized and Follow-up N 268
Feit, F,et al Circulation 2000;101:2796
Impact of Diabetes on 7-year Survival in BARI
100
All Patients 844 809
Survival
80 60 40 20 0
CABG n914 PTCA n915 p 00425
0
1
2
3
4
5
6
7
868 864
100
Survival
Patients with Treated Diabetes
100
764 80 557 CABG n180 PTCA n173 p 00011
Patients without Treated Diabetes
80 60 40 20 0
0 1 2 3 4
60 40 20
CABG n734 PTCA n742 p 07155
5
6
7
0 Years
0
1
2
3
4
5
6
7
BARI Investigators J Am Coll Cardiol 2000;35:1122-1129
BARI Randomized Trial Final 10 Year Data
Freedom from Cardiac Death
Follow-up Time in Years
No of Patients CABG PTCA 914 915 859 842 812 790 737 714 553 540
JACC 2007; 49: 1600-6
BARI Randomized Trial
Final 10 Year Data
JACC 2007; 49: 1600-6
BARI Randomized Trial
Final 10 Year Data
Survival
Follow-up Time in Years
No of Patients ND CABG 734 ND PTCA 742 D CABG D PTCA 180 173 698 703 161 139 669 675 143 115 613 621 124 93
473 477 80 63
JACC 2007; 49: 1600-6
Predictors of Mortality - BARI
10 08
Mortality
Mortality in Patients without Q-MI
10 08
Mortality
Mortality in Patients After Q-MI
079
DM-PTCA DM-CABG
Non DM-CABG
06 04 02 00
0
06 04
Non DM-PTCA
029 027 017
022 016 007 006 006
02 00
1 2 3 4 Follow-up years
5
0
1
2
3
4
5
Years after Q-MI
Detre KM et al N Engl J Med 2000;342:989-997
BARI Overall Survival Randomized vs Registry Stratified by Treatment
100 80
Survival
CABG Patients
858 844
100 80
Survival
PTCA Patients
861 809
60 40 20 0
0 1 2 34 Years
590 860
60 40 20 0
Unadjusted p57 Adjusted p66
Unadjusted p01 Adjusted p16
Registry Randomized
5 6 7
Registry Randomized
0 1 2 34 Years
1124 842
5
6
7
Number of CABG Patients Registry 625 Randomized 914
569 814
Number of CABG Patients 436 Registry 1189 590 Randomized 915
1091 790
769 579
BARI Registry Patients PTCA vs CABG Relative Risks for Mortality
Seven Year Survival Unadjusted 99 CI Adjusted 99
CABG OVERALL Registry Eligibility Criteria UA/Non Q-MI Stable Angina Diabetes Status No Diabetes 885 740 832 919 858
PTCA Unadj p Adj p 861 66 86
Relative Risk
for the Risk
864 859
11 079
29 003
883
740
88 96
45 80
PTCA Better CABG Better PTCA Better CABG Better
Treated Diabetes
BARI 2D: Overview
Revasc IP Strategy
Diabetes Clinic - q mo x 6, - then q 3 mo ECG q yr
2600 pts with -type 2 diabetes -ischemia -CAD
Revasc IS Strategy
Primary Endpoint: 5 year Mortality
Med Rx IP Strategy
QOL, q yr Diabetes complication assessment q yr
Med Rx IS Strategy
MASS Registry: CABG vs PCI vs Medical Therapy 5 Year Cardiac Death
Free of cardiac-related death
Months Patients at risk
Patients CABG PCI MT 221 120 158 One Yr 197 82 136 Two Yrs 192 77 112 Three Yrs 186 73 97 Four Yrs 162 67 89 Five Yrs 136 61 81
Hueb W et al; Ann Thorac Surg 2007; 83:93-9
MASS Registry: CABG vs PCI vs Medical Therapy
5 Year Event Free Survival
Event-free survival
Months after study entry Patients at risk
Patients CABG PCI MT 221 120 158 One Yr 197 111 146 Two Yrs 193 108 136 Three Yrs 189 107 123 Four Yrs 169 105 106 Five Yrs 152 100 99
Hueb W et al; Ann Thorac Surg 2007; 83:93-9
CABG Outcomes in Patients with Diabetes
Odds Ratio 95 CI
Operative Death Adjusted Diabetes overall Oral medication Insulin 12 12-13 1110-12 1413-15
Morbidity Adjusted 14 13-14 1312-13 1615-17
Infection Adjusted 14
13-14 1212-13 1615-17
Carson et al JACC 40; 2002: 421
Mechanical Revascularization for Coronary Artery Disease in Diabetics Clinical Characteristics Prognosis After MI Balloon PCI Comparison with CABG Bare Metal Stent PCI DES impact on PCI outcomes
Impact of Diabetes on Short- and Long-Term Outcomes of PCI
Predictors of TLR n6186
Ref Diam per mm Lesion length per 5 mm Diabetes
1-year mortality n6534
Diabetes No Diabetes 33
RR15
P0012
21
Current Smoker Prior MI
0
1
2
Cutlip DE et al JACC 2002;40:2082-9
Bhatt et al JACC 2000;35:922-8
PCI in Diabetics in the Bare Metal Stent Era
Relative Risk Nondiabetic n8798 Death MI Death/MI TVR Death/MI/TVR 100 100 100 100 100 Diabetic n2684 250 153 179 141 145 p 001 001 001 001 001
Mathew et al Circ 2004 ;109; 478
PCI in Diabetics in the Bare Metal Stent Era
New Lesion Formation
Nondiabetic n15 
48 New lesions New lesions in treated vessels 396 26 Diabetic n470 142 30 p 005
181 12
72 15
004
Mathew et al Circ 2004 ;109; 478
Restenosis in Diabetics Subtraction Graph
West et al Circ 2004; 109:870
Vessel Patency and Survival in Diabetics
Van Belle et al Circ 2001;103, 1221
Bare Metal Multivessel Stenting in Diabetics
Mehran et
al JACC 43:2004; 1352
The ARTS Trial: CABG vs Stent Outcomes in Diabetics
208/1205 17 pts had diabetes
10 8 6
P019 P009
50
393 63
P0003
40
63
4 2 0 Death CVA
31
18
30 20
177
12 month Events:
Stent CABG
10 0 Death, MI, CVA, TVR
Abciximab and Diabetes
4 Placebo Abciximab 3
Death
2
1
0
0 50 100 150 200 250 300 350
P 0010 Days from Randomization
Bhatt et al Circulation 2000;35:924
Are Gp2b/3a Inhibitors Still Beneficial in the High-Dose Clopidogrel Era?
1-Year Outcomes
12
ISAR-SWEET Trial
Placebo
Abciximab
PNS for all comparisons
8 83 86
701 diabetic patients 28 IDDM, 20 diet alone undergoing elective PCI Excluded any recent MI or ACS, angiographic thrombus, EF30 All pretreated with clopidogrel 600 mg at least 2 hrs prior to PCI
4
48
51
48
43
Randomized to abciximab vs placebo Primary Endpoint: 1-year D/MI
0
Death
MI
Death or MI
Mehilli J et al Circulation 2004;110:3627-35
Issues with ISAR-SWEET
Enrolled only low-risk diabetic patients
Observed 1-yr D/MI 8 vs 14 expected
Trial underpowered to detect clinically meaningful differences in ischemic complications
Does not exclude a 40 reduction in 1-yr death or MI
At the present time, there is
insufficient evidence to conclude that Gp2b/3a inhibitors do not provide substantial benefit for diabetic pts undergoing PCI
Mechanical Revascularization for Coronary Artery Disease in Diabetics Clinical Characteristics Prognosis After MI Balloon PCI Comparison with CABG Bare Metal Stent PCI Drug Eluting Stents Impact on PCI Outcomes
SIRIUS Subgroup TLR at 1 Year
Sirolimus Control
Overall Male Female 49 52 41 84 37 60 41 200 205 190 264 176 230 180 223 182 186 219 232 186
0 01 02 03
p-value
00001 00001 00002
events prevented per 1,000 patients 152 153 149
Diabetes
No Diabetes LAD Non-LAD Non-
00002
00001 00001 00001 00001 00001 00001 00001 00001 00001
04 05 06 07 08 09 10 09 08 07
180
138 170 140 157 151 146 158 175 141
Small Vessel 275 66 Large Vessel Short Lesion 31 40
Long Lesion 135 60 Overlap No Overlap 57 45
Hazards Ratio 95 CI
Pooled TAXUS Trials II, IV, VI
Overall Diabetic Subset: Angiographic Restenosis
50 40
375
30 20 10 0
52
87 P0001
331
80 P0001
74
In-stent restenosis
n263
In-segment restenosis
n264
SES vs Bare Metal in Diabetes
Sabate, M et al Circulation 2005;112:2175-2183
SES vs Bare Metal in Diabetes
Sabate, M et al Circulation
2005;112:2175-2183
SIRIUS DM- Subanalysis
In-Segment Restenosis and TLR 12 Months
60
505 507 50
50 40
35
30 20 10 0
176
223
238 139 44
208
123 72
Restenosis TLR
Restenosis
TLR
Restenosis TLR
Overall
Oral Agents
Insulin
2 Year Safety and Efficacy of DES
TVR MACE
Relative Risk
Relative Risk
DES better
BMS better
DES better
BMS better 50
Marzocchi et al Circ 2007; 115:3181-3188
Multivariate Predictors of 2-Year TVR
All Patients
HR
DES Diabetes mellitus Prior MI Prior PCI Prior CABG Proximal LAD treatment In-stent restenosis Ostial lesion Reference vessel diameter Total lesion length 075 126 081 136 132 125 189 134 071 1007
95 CI
064-088 109-146 069-096 109-170 105-167 108-145 124-289 111-162 061-082 100-101
P
00004 0002 001 0008 002 0003 0003 0002 00001 002
Marzocchi et al Circ 2007; 115:3181-3188
51
Multivariate Predictors of 2-Year TVR DES group
HR 95 CI P
Diabetes mellitus Reference vessel diameter Renal Failure
136 064 169
106-176 045-093 106-268
002 002 003
Marzocchi et al Circ 2007; 115:3181-3188
52
Independent Predictors of TVR after DES:
RESEARCH and T-SEARCH Results
Angio Restenosis n238
ISR rx Ostial lesion Diabetes Stent length per 10
mm Ref diam per mm LAD
1-year MACE n1084
Cardiogenic Shock Female
RR 26
Multivessel Dz Diabetes Left main stenting
RR 16
Bifurcation stenting
01
1
10
01
1
10
Lemos PA et al Circulation 2004;109:1366-70
Ong ATL, et al JACC 2005;45:1135-41
Do Diabetics Have Increased Mortality After Multivessel Stenting?
Study yrs f/u Study yrs f/u BARI 8 BARI 8 EAST 8 EAST 8 BARI registry 5 BARI registry 5 Duke databank 6 Duke databank 6 Emory databank 5 Emory databank 5 NNE 2 NNE 2 ARTS 3 ARTS 3 SOS 1 SOS 1
Yellow Stent vs CABG
Type of Type of Study Study RCT RCT RCT RCT Obs Obs Obs Obs Obs Obs Obs Obs RCT RCT RCT RCT
N N 353 353 90 90 339 339 770 770 889 889 2766 2766 210 210 142 142
Adjusted Adjusted Hazard Ratio Hazard Ratio 187 187 156 156 129 129 127 127 135 135 149 149 170 170 10 10
P005
Summary: Stents do not appear to have significantly attenuated the Summary: Stents do not appear to have significantly attenuated the mortality advantage of CABG in multivessel CAD mortality advantage of CABG in multivessel CAD
FREEDOM Trial
Multivessel Sirolimus Stenting vs Surgery in Diabetics
Eligibility: Type II DM patients with MV-CAD eligible for stent or surgery Exclude:
Patients with acute STEMI, cardiogenic shock
2300 pts Randomized 1:1
MV-stenting with sirolimus and abciximab
CABG with or without CPB
All concomitant Meds shown to be beneficial are encouraged, including: Plavix, ACE inhibitors, beta blockers, statins, etc
Primary Endpoint: 5-year mortality Secondary Endpoint: MACE/stroke at 12 months
Multivariate Predictors of Stent Thrombosis
Odds Ratio Confidence Limits P
Age Male History of CABG In hospital Renal failure IDDM Bifurcation lesion In-stent restenosis Lack of clopidogrel therapy
097 066 015 375 20 44 45 021
094-10 031-104 001-12 12-113 084-49 196-100 18-114 009-049
006 027 004 00183 012 00004 00013 00003
57
Kuchulakantiet al Circulation 2006;113:1108-1113
Choosing Between PCI and CABG in Diabetic Patients
1
2
CABG is always preferred over PCI if significant stenosis of the left main coronary artery is present CABG is preferred over PCI for three-vessel CAD or twovessel CAD with a significant lesion 70 of the proximal LAD PCI may be a reasonable alternative based on patient preference if an equivalent degree of revascularization can be achieved However, the most recent PCI guidelines 2001 consider proximal LAD
involvement less well established for PCI therapy
Choosing Between PCI and CABG in Diabetic Patients
3 PCI is preferred over CABG for single vessel CAD or twovessel CAD not involving the proximal LAD if an equivalent degree of revascularization can be achieved 4 In high-risk CABG patients, either revascularization strategy may be advisable and the choice should be individualized for each patient
Specific Recommendations for Diabetic Patients Undergoing PCI
1
2
Drug-eluting stents, either rapamycin or paclitaxel, should always be used when feasible The use of GP IIb/IIIa inhibitors is strongly recommended, especially in the setting of an ACS
Secondary Coronary Prevention in Diabetes
Intervention High-intensity statin Evidence HPS: 27 in CHD death or MI among DM subgroup 20 in CHD death, p002
Secondary Coronary Prevention in Diabetes
Intervention High-intensity statin Evidence HPS: 27 in CHD death or MI among DM subgroup 20 in CHD death, p002 HOPE diabetic substudy: 25 in CVdeath/MI/stroke p0001; 37 in CVdeath over 5 yr follow-up p0001
ACE-Inhibitor
Secondary Coronary Prevention in Diabetes
Intervention High-intensity statin Evidence HPS: 27 in CHD death or MI among DM
subgroup 20 in CHD death, p002 HOPE diabetic substudy: 25 in CVdeath/MI/stroke p0001; 37 in CVdeath over 5 yr follow-up p0001 Clearcut benefits on microvascular complications UKPDS trial Observational studies suggest improved CV outcomes and less restenosis associated with lower HbA1c ? Specific benefit of glitazones
ACE-Inhibitor
Intensive glycemic control
Diabetes Management
Flaherty and Davidson CJ JAMA 2005;293:1501
Thats all folks
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