Lecture given at the 2010 Diabetes Philippines annual convention

1. Revascularization vs
Medical Treatment
for Coronary
Disease in Diabetes
Iris Thiele Isip Tan MD, FPCP, FPSEM
Clinical Associate Professor, UP College of Medicine
Section of Endocrinology, Diabetes & Metabolism
Department of Medicine, Philippine General Hospital

2. Disclosure
I’m not a cardiologist :)
“Heads, you get a quadruple bypass.
Tails, you take a baby aspirin.”

3. When does CABG offer
benefits over PCI?
When can
revascularization be
offered to patients on
medical therapy?
Who should be screened
for CAD?

4. Who should be
screened for CAD?
Silent myocardial
infarction (SMI) is more
frequent in diabetes
Which asymptomatic
diabetic should be
screened?
Which is the more
appropriate non-invasive
test to determine the
presence of CAD?
CAD accounts for
>75% of deaths in
diabetes

5. Screening for
CAD in diabetes
Other atherosclerotic
vascular disease
Microalbuminuria and
chronic kidney disease
Abnormal resting ECG
Autonomic neuropathy
Retinopathy
Hyperglycemia
Age & sex
Unexplained dyspnea
Multiple cardiac risk
factors
ADA (2007)
Bax et al Diabetes Care 2007;30:2729-36

6. Exercise ECG to
screen high-risk
patients
Ischemia imaging
as initial strategy
only in patients with
abnormal resting
ECGs
ADA (1998)
Bax et al Diabetes Care 2007;30:2729-36

7. Cardiac CT*
using electron beam or multislice
technology
If medical goals
cannot be met
Those with strong
clinical suspicion of
very-high-risk CAD
Bax et al Diabetes Care 2007;30:2729-36
ADA (2007)
* AHA Class IIB recommendation
for intermediate risk

8. Further testing if
coronary calcium
score >400 considering
age and renal function
Bax et al Diabetes Care 2007;30:2729-36
Calcium score
1-10 minimal CAD
11-100 mild
101-400 moderate
>400 extensive
ADA (2007)

9. First CHD events and stroke
Median follow-up: 4 years
Coronary artery calcium score (CACS)
+ risk factors (lipoprotein, apolipoprotein,
homocysteine, CRP, HOMA-IR, UAC ratio)
589 T2DM with no history of CVD
O:
I:
P:
PREDICT
RCT
Elkeles et al Eu Heart J 2008;29:2244-51

10. e 2 Primary endpoint event rates in successive categories of coronary artery calcification score. Each unit increase in log2 (CACSþ1)
ents a doubling in CACS. The calcification score categories 0–10, 11–100, 101–400, 401–1000, and 1001–10000 include log-
rmed CACS categories 1–4, 4–7, 7–9, 9–10, and 11, respectively. Dotted lines show 95% confidence intervals.
DICT study 224
CACS
Independent Predictor of CHD/stroke
66 CV events (10 strokes)
Elkeles et al Eu Heart J 2008;29:2244-51
Doubling of CACS = 29% risk
PREDICT

11. Further testing if
coronary calcium
score >400 considering
age and renal function
SPECT: myocardial perfusion
Stress echocardiography:
ischemic wall motion
abnormalities
Bax et al Diabetes Care 2007;30:2729-36
ADA (2007)

12. Cardiac death or nonfatal MI
No screening vs adenosine-stress
radionuclide myocardial perfusion
imaging (MPI)
1123 T2DM and no symptoms of CAD
O:
I:
P:
DIAD
Young LH et al JAMA 2009;301(15):1547-55
RCT

13. Young LH et al JAMA 2009;301(15):1547-55
DIAD
HR 0.88; 95%CI (0.44,1.80)
p=0.73
15 events
17 events
Cumulative Incidence of Cardiac Events
Low event rate
2.9% over 5 y
(0.6%/yr)

14. NPV
normal MPI 98%
PPV
Any abnormality 6%
Mod/large defects 12%
Cumulative
Incidence of
Cardiac Events
by Screening
Group
Young LH et al JAMA 2009;301(15):1547-55

15. Routine screening for inducible
ischemia in asymptomatic T2DM
not advocated
Low yield of detecting significant
inducible ischemia
Low overall cardiac event rate
Routine screening does not appear
to affect overall outcome
Prohibitively expensive
Young LH et al JAMA 2009;301(15):1547-55

16. Further testing if
coronary calcium
score >400 considering
age and renal function
SPECT: myocardial perfusion
Stress echocardiography:
ischemic wall motion
abnormalities
Bax et al Diabetes Care 2007;30:2729-36
Stress echo?
ADA (2007)

17. Non-fatal MI, late myocardial
revascularization and cardiac death
Symptom-limited treadmill exercise
testing (Bruce protocol) + 2-D echo at
rest and immediately after exercise
193 T2DM with suspected or known CAD
referred for EE
O:
I:
Prognostic Value of Exercise Echo (EE)
P:
Oliveira JLM et al Cardiovascular Ultrasound 2009;7:24
Retrospective

18. Oliveira JLM et al Cardiovascular Ultrasound 2009;7:24
Survival Free of Cardiac Events
Kaplan-Meier curves
Normal
Abnormal
RR 3.63, 95%CI (1.09-6.02) p=0.03
Cardiac events
+ EE 20.6%
- EE 7%

19. Serial testing?
Low cardiac event rate
within 2 years after
normal stress
myocardial perfusion
or echo studies
Bax et al Diabetes Care 2007;30:2729-36
progressive
atherosclerosis
Warranty

20. Suspect CAD
Fuster V & Farkouh ME. Circulation 2010;121:2540-52

21. Suspect CAD
Asymptomatic
Selective
ischemia
assessment
Myocardial
perfusion imaging
Fuster V & Farkouh ME. Circulation 2010;121:2540-52

22. Suspect CAD
Mild to moderate
symptoms
CCS Class I, II
Normal or single
segment abnormal
OMT
Asymptomatic
Selective
ischemia
assessment
Myocardial
perfusion imaging
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
Fuster V & Farkouh ME. Circulation 2010;121:2540-52

23. Suspect CAD
Mild to moderate
symptoms
CCS Class I, II
Normal or single
segment abnormal
Multisegmental
abnormalities
OMT
Coronary
angiography
Asymptomatic
Selective
ischemia
assessment
Myocardial
perfusion imaging
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
Fuster V & Farkouh ME. Circulation 2010;121:2540-52

24. Suspect CAD
Mild to moderate
symptoms
CCS Class I, II
Significant symptoms
CCS Class III, IV
Normal or single
segment abnormal
Multisegmental
abnormalities
OMT
Coronary
angiography
Asymptomatic
Selective
ischemia
assessment
Myocardial
perfusion imaging
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
Fuster V & Farkouh ME. Circulation 2010;121:2540-52

25. When does CABG offer
benefits over PCI?
When can
revascularization be
offered to patients on
medical therapy?
Who should be screened
for CAD?

26. Primary - all-cause mortality
Secondary - composite of death, MI or
stroke
Prompt revascularization with intensive
medical therapy vs intensive medical
therapy alone
2368 T2DM with heart disease
BARI 2D
O:
I:
P:
RCT
BARI 2D Study Group. NEJM 2009;11:360(24):2503-15

27. Hypothesis
Prompt
revascularization
would reduce long-
term rates of death
and CV events, as
compared with
medical therapy
alone.
BARI 2D Study Group. NEJM 2009;11:360(24):2503-15

28. BARI 2D Study Group. NEJM 2009;11:360(24):2503-15
Medical therapy
Insulin-
sensitization
Medical therapy
Insulin-provision
therapy
Prompt
revascularization
Insulin-provision
therapy
Prompt
revascularization
Insulin-
sensitization
CABG
PCI
Stratified
randomization
facto"al
2 x 2

29. Prompt
revascularization
Undergo procedure within 4
weeks after randomization
Stratified randomization:
PCI or CABG
BARI 2D Study Group. NEJM 2009;360(24):2503-15

30. Medical therapy
for all patients
HbA1c <7%
LDL <100 mg/dL
BP <130/80 mm Hg
Counseling on smoking cessation,
weight loss and regular exercise
Feedback on risk factor control
Follow-up monthly for first 6 months
then q3 months thereafter
BARI 2D Study Group. NEJM 2009;360(24):2503-15

31. BARI 2D Study Group. NEJM 2009;360(24):2503-15

32. BARI 2D Study Group. NEJM 2009;360(24):2503-15

33. BARI 2D Study Group. NEJM 2009;360(24):2503-15
Non-fatal MI
Revascularization grp 7.4%
Medical therapy 14.6%

34. Myocardial Jeopardy Index (MJI)
percentage of myocardial segments supplied by
significantly diseased coronary arteries or their branches

35. Coronary
angiography
Fuster V & Farkouh ME. Circulation 2010;121:2540-52
Mild to moderate
symptoms
CCS Class I, II
Significant symptoms
CCS Class III, IV
MJI = Myocardial Jeopardy Index

36. Coronary
angiography
Fuster V & Farkouh ME. Circulation 2010;121:2540-52
Normal or
non-obstructive
Mild to moderate
symptoms
CCS Class I, II
Significant symptoms
CCS Class III, IV
OMT
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
MJI = Myocardial Jeopardy Index

37. Coronary
angiography
Fuster V & Farkouh ME. Circulation 2010;121:2540-52
Normal or
non-obstructive
Mild to moderate
symptoms
CCS Class I, II
Significant symptoms
CCS Class III, IV
Non-
obstructive
OMT
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
MJI = Myocardial Jeopardy Index

38. Coronary
angiography
Fuster V & Farkouh ME. Circulation 2010;121:2540-52
Normal or
non-obstructive
Mild to moderate
symptoms
CCS Class I, II
Significant symptoms
CCS Class III, IV
Obstructive
AND low MJI
Deferred
revascularization
+ OMT
Non-
obstructive
OMT
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
MJI = Myocardial Jeopardy Index

39. Coronary
angiography
Fuster V & Farkouh ME. Circulation 2010;121:2540-52
Normal or
non-obstructive
Mild to moderate
symptoms
CCS Class I, II
Significant symptoms
CCS Class III, IV
Obstructive
AND low MJI
Obstructive
AND high MJI
Deferred
revascularization
+ OMT
Prompt
revascularization
+ OMT
Obstructive
Non-
obstructive
OMT
Optimal
medical therapy
BP <130/80
LDL <70
HbA1c <7%
MJI = Myocardial Jeopardy Index

40. When does CABG offer
benefits over PCI?
When can
revascularization be
offered to patients on
medical therapy?
Who should be screened
for CAD?

42. Tempting but
incorrect to conclude
from BARI 2D
... for type 2 DM with
severe angiographic
CAD, CABG is better
than PCI
Rutter MK & Nesto RW. Heart 2010;96:1436-40

43. Rutter MK & Nesto RW. Heart 2010;96:1436-40
Evidence-based appropriate therapy for CAD in diabetes
by symptom and/or disease severity

44. original BARI study
Diabetes subgroup
CABG with significantly better 5-year (80%
vs 67%) and 10-year (58% vs 46%, p=0.025)
survival when compared to balloon PCI
CABG vs PCI
1829 patients (most had unstable angina
and multivessel disease)
O:
I:
P:
BARI Investigators. NEJM 1996;335:217-25
RCT

45. Coronary Artery Revascularization
in Diabetes (CARDia)
Underpowered to compare individual outcomes
Composite (death, stroke or MI) similar
for CABG and PCI-treated (10.5% vs 13%,
p=0.39); More repeat procedures with PCI
CABG or PCI with abciximab and
stenting
510 diabetics with multivessel or complex
single-vessel CAD
O:
I:
P:
RCT
Kapur A et al. J Am Coll Cardiol 2010;55:432-40

46. SYNergy between PCI with TAXus
and cardiac surgery (SYNTAX)
More major cardiac and cerebrovascular
events with PCI (26% vs 14%, p=0.003)
PCI mortality higher for highly complex
lesions (13.5% vs 4.1%, p=0.003)
CABG vs PCI (paclitaxel-eluting stents)
Post hoc data for those with diabetes
1800 patients with complex left main or
three-vessel disease (452 with diabetes)
O:
I:
P:
RCT
one-year data
Banning AP et al. J Am Coll Cardiol 2010;55:1067-75

47. Future REvascularization Evaluation in Patients
with Diabetes: Optimal Management of
Multivessel Disease (FREEDOM)
Total and CVD mortality at 1-5 years
Quality of life and cost-effectiveness
CABG vs DES stent PCI in the setting
of optimal medical therapy
~2058 patients with diabetes and
multivessel disease
O:
I:
P:
Farkouh et al. Am Heart J 2008;155:215-23
RCT

48. JNJhealth “Coronary Stent Animation” 3 Sept 2008,
http://www.youtube.com/watch?v=9FPapBbbS4o&feature=channel. Accessed 25 Oct 2010
Coronary grafts bypass proximal segments of vessels
taking many atheromatous lesions out of play
Stents leave behind substantial coronary plaque

49. Summary
Type 2 diabetes
CABG best for
multivessel CAD and/or
LV systolic dysfunction
PCI with DES is
equivalent to CABG in
single-vessel disease
and normal LV systolic
function
Page BJ et al. Curr Diab Rep 2010;10:10-15

50. When does CABG offer
benefits over PCI?
When can
revascularization be
offered to patients on
medical therapy?
Who should be screened
for CAD?

51. #ank Y$
http://www.endocrine-witch.net