Untitled

Preventive Effects of
Rosiglitazone on Restenosis
after Coronary Stenting in
Patients with Type 2 Diabetes
Donghoon Choi, MD, PhD
Cardiology Division
Yonsei University College of Medicine,
Background
1. Cardiovascular disease is one of the important leading cause of deaths in Type 2 diabetic patients.
2. As a result of dramatic increase in implantation numbers, in-stent restenosis has been significant clinical and socio-economic problems.
3. The in-stent restenosis rate after coronary stenting has reached up to 45-50 % in type 2 DM patients comparing to 15-25% in non-diabetic patients.
4. The most effective treatment modality for in-stent Pathogenesis of Restenosis
Growth factors & cytokines
Receptor activation
Smooth muscle cell
Cell proliferation
Extracellular matrix
Migration
Synthesis & secretion
Approaches for Restenosis
Prevention
Inflammation
Migration
Proliferation
Reduce injury 1. Enhance biocompatibility
2. Anti-inflammatory
Antimigratory
Antiproliferative
Promote healing
& reendotheliali-
Atherogenic Effects of PPARγ Ligands
in the Vasculature
Monocytes
Endothelial Cells
↓ Atherosclerosis
Male OLETF rat, Balloon injury at 16 weeks
and pioglitazone for 3weeks
Intima area
Intima/media ratio
Pioglitazone
Pioglitazone
TZDs: effects on carotid arterial intimal and medial co Troglitazone 400 mg/day
IMT (mm)
∆
Japanese subjects with type 2 diabetes*P < 0.001 vs. control Minamikawa J, et al. J Clin Endocrinol Metab 1998; 83:1818–1820.
Study Purpose
• To investigate the preventive effect of PPAR- γ agonist, rosiglitazone on restenosis after coronary stenting in type II DM patients.
=> 6 month follow-up angiographic binary Subjects (I)
- Type II DM patients undergoing coronary stenting at YUMC (Nov. 2001 ~ Dec. 2002) - LVEF < 40% or evidence of CHF- GOT/GPT > 2 x upper limit of normal range- Cr > 2.0 mg/DL - Previous CABG- Primary PTCA Subjects (II)
Study design and Method
• Anthropometry, Serologic lab : initial and 6 month • Rosiglotazone : at least 8mg before angiography, • Control Blood Sugar : continue individual conventional therapy (sulfonylurea, biguanide, Baseline Characteristics
Rosiglitazone
No. (male/female)
45 (34/11)
38 (24/14)
Age (years)
59.9±9.3
60.9±9.3
DM duration (years)
7.2±3.8
7.5±4.9
BMI (kg/cm2)
24.8±3.35
24.9±2.96
Fasting glucose (mg/dL)
150.3±28.4
160.3±34.4
HbA1c (%)
7.72±1.13
7.79±1.30
Fasting insulin (µU/mL)
4.97±2.51
5.60±2.70
Total cholesterol (mg/dL)
191.1±48.9
190.5±37.6
HDL-cholesterol (mg/dL)
41.1±10.9
38.9±11.0
Triglyceride (mg/dL)
159.5±55.1
167.7±60.8
Free fatty acid (µmol/L)
580.3±101.7
669.2±127.4
hsCRP (mg/L)
2.01±1.33
2.92±1.98
Medications
Rosiglitazone
Treatments: No. (%)
HMG-CoA reductase
37 (88.1)
31 (81.6)
inhibitor
ACE inhibitors
30 (71.4)
28 (73.7)
Antiplatelet agents
38 (90.5)
34 (89.5)
Sulfonylureas
26 (61.9)
25 (65.8)
Biguanides
22 (52.3)
21 (55.3)
α-glucosidase inhibitor
15 (35.7)
10 (26.3)
Baseline Angiographic
Characteristics
Rosiglitazone
Stented coronary vessels
Left main
Reference diameter (mm)
3.15±0.49
3.16±0.49
Minimum lumen diameter
0.65±0.41
0.83±0.57
Diameter stenosis (%)
79.4±12.8
74.4±15.8
Lesion length (mm)
16.48±5.16
19.02±6.09
<0.05
Post-stenting Angiographic Data
Rosiglitazone
Stent diameter (mm)
3.24±0.42
3.29±0.41
Stent length (mm)
18.40±4.75
20.28±5.73
Post-stenting
3.10±0.43
3.13±0.48
Diameter stenosis (%)
2.49±4.26
2.25±4.44
Acute gain (mm)
2.45±0.57
2.30±0.53
Follow-up Biochemical
Characteristics
Rosiglitazone
Baseline FU
Baseline FU
Fasting glucose (mmol/l)
8.34±1.58 6.87±1.52
8.90±1.91 7.35±1.89
HbA1c (%)
7.72±1.13 7.23±0.93
7.79±1.30 7.17±0.98
Fasting insulin (pmol/l)
35.7±18.0 34.2±18.9
40.2±19.4 34.5±19.7
HDL-cholesterol (mmol/l)
1.06±0.28 1.14±0.27
1.01±0.28 1.12±0.21
Triglyceride (mmol/l)
1.80±0.62 1.43±0.69
1.89±0.69 1.34±0.44
Free fatty acid (µmol/L)
580.3±101.7 548±95.6
669.2±127.4 492.0±101.4
hsCRP (mg/L)
2.01±1.33 1.79±1.22
2.92±1.98 0.62±0.44
Follow-Up Angiographic Data
Rosiglitazone
1.91±1.05
2.49±0.88
Diameter Stenosis (%)
40.60±31.90
23.00±23.40
Lumen loss (mm)
1.20±0.97
0.65±0.73
Loss index
0.49±0.42
0.29±0.31
Restenosis rate (%)
Clinical Follow-Up Data
Target lesion
revascularization
MACE
The Effects of Rosiglitazone
on VSMC migration
at 48 weeks (mm)
Change in m
Baseline 0.815
Progression rate
(mm/48 weeks) = 0.031
– 0.012*
IMT = intima-media thicknessPatients with clinically stable coronary artery disease without diabetes RSG dose 4 mg/day for initial 8 weeks; 8 mg/day for remaining 40 weeks*P = 0.03 vs. PBO Sidhu JS, et al. Arterioscler Thromb Vasc Biol 2004; 24:930–934.
Conclusion
• In this study, rosiglitazone has dramatically reduced restenosis rate of CAOD pateintswith coronary stenting in Type 2 diabetes.
• In type 2 diabetes patients with CAOD, using PPAR-γ agonist, not only for glucose lowering and insulin sensitizing effect, but also for anti-inflammatory effect, has to be strongly considered.

Source: http://www.summitmd.com/pdf/pdf/050923_lec7.pdf