1. Clopidogrel Use and Death/MI After Stent Implantation in a Diabetic Population Somjot S. Brar, Simerjeet K. Brar, John Kim, Ray Zadegan, Michael Ree, In-lu A. Liu, Prakash Mansukhani, Vicken Aharonian, Ric Hyett, Albert Y-J. Shen Department of Cardiology Kaiser Permanente, Los Angeles & UCLA School of Medicine Kaiser Permanente Results from the SUNSET registry SCAI ‘07

2. Disclosures Research grant support from Boston Scientific –S. Brar, MD –A. Shen, MD Kaiser Permanente

3. Background  Death / MI reportedly increased with DES compared to BMS.  Two prior landmark analysis show increased death / MI in DES compared to BMS.  BASKET-LATE  Eisenstein et al.  Limited data in patients with diabetes.  Duration of clopidogrel after PCI remains unknown.

4. Study Questions  Is death / MI influenced by:  Clopidogrel duration?  Stent type (DES, BMS)?  Among patients taking clopidogrel for ≤ 6 months, is death / MI more frequent with DES compared to BMS? Kaiser Permanente

5. Methods Study date: January 2002 – December 2005 Study type: observational using the SUNSET registry Population: –consecutive diabetic patients undergoing first PCI –No prior PCI or CABG –Multiple stent types not permitted –Insured members of a prepaid integrated health plan Location: high volume tertiary care referral center (Los Angeles, CA) Main outcome measure: death or MI at 18 months (545 days) post PCI Kaiser Permanente

6. Methods Clopidogrel –pharmacy prescription records –Duration of clopidogrel calculated from index PCI –User: >6 months of clopidogrel use from index PCI date –Non-users: ≤6 months of use from the index PCI date “Landmark” analysis –Excluded patients with events within first 6 months –Similar to an observational analysis from BASKET- LATE. Kaiser Permanente

7. Study Flow 749 diabetics underwent first revascularization 671 event free from Death or MI at 6 months Exclusion: 41 Death/MI/Revascularization 37 Clopidogrel usage unknown F/U to 18 months post PCI Kaiser Permanente

8. DES (n=450) Four Study Groups: Stratified by Stent Type & Clopidogrel 671 Patients Clopidogrel / Stent type Clopidogrel (-) N=74 Clopidogrel (+) N=147 Clopidogrel (-) N=127 Clopidogrel (+) N=323 Death or MI (18 months) BMS (n=221) Kaiser Permanente

9. Baseline Characteristics Clopidogrel UserClopidogrel Non-user DESBMSDESBMS Age61.5 ± 10.264.3 ± 10.263.3 ± 12.164.0 ± 11.6 Female30.1%29.9%33.9%36.5% Insulin20.7%20.4%31.5%27.0% HgA1c7.4 ± 1.77.6 ± 1.87.3 ± 1.67.6 ± 1.9 LDL114 ± 37122 ± 39103 ± 36111 ± 41 Creatinine1.2 ± 1.11.1 ± 0.71.3 ± 1.31.3 ± 1.6 Hemoglobin13.5 ± 1.713.3 ± 1.713.3 ± 2.013.0 ± 1.7 Ejection fraction0.61 ± 0.150.63 ± 0.150.62 ± 0.150.59 ± 0.16 BMI30.7 ± 6.230.0 ± 5.930.1 ± 5.829.4 ± 5.9 Clopidogrel dur. >6 mo71.8%66.5% dur. >9mo55.3%48.9% dur >12mo22.9%21.3%

10. Baseline Characteristics Clopidogrel UserClopidogrel Non-user DESBMSDESBMS Stent No. of Stents 1.4 ± 0.6 1.3 ± 0.71.5 ± 0.7 Mean diameter (mm) 2.9 ± 0.33.2 ± 0.53.0 ± 0.33.0 ± 0.5 Total cumulative stent length (mm) 26.9 ± 13.420.1 ± 10.225.1 ± 14.021.8 ± 9.9 Stent Location LAD 50.5%42.2%44.9%41.9% Diagonal 4.0%2.7%1.6%0% Circumflex 16.4%20.4%19.7%18.9% Obtuse marginal 9.9%10.2%8.7%12.2% RCA 28.8%35.4%30.7%31.1% PDA / PLV 3.1%2.7%3.9%8.1% Ramus 0.9%0%2.4%1.4%

11. Death / MI by Stent type (0d – 18mo) Cumulative Incidence (%) 0 0 55 10 15 20 No. at Risk DES BMS 498469459 251237225 320 218 p=0.05

12. Death / MI by Stent Type (6mo – 18mo) 0 5 Cumulative Incidence (%) p=0.08 10 3.1% 6.2%

13. Death / MI in BMS group (6mo – 18mo) 0 10 20 Cumulative Incidence (%) 3.5% 12.2% p=0.01

14. Death / MI in DES group (6mo – 18mo) 0 10 20 Cumulative Incidence (%) 2.2% 5.5% p=0.07

15. Death / MI in Clopidogrel Non-Users (6mo – 18mo) 0 10 20 Cumulative Incidence (%) 5.5% 12.2% 30 p=0.11

16. Death / MI by Clopidogrel Duration (6mo – 18mo) 10 20 Cumulative Incidence (%) 2.0% 1.0% 7.3% (64% DES) (69% DES) (71% DES) p= 0.27 0 <9 months (n=314) 9-12 months (n=207) >12 months (n=150) p=0.0005

17. Discussion From index PCI date to 18 months, death / MI less with DES vs. BMS (p=0.05). Landmark Analysis –Clopidogrel use was associated with less death / MI in both DES (p=0.07) and BMS groups (p=0.01). –Among clopidogrel non-users, death / MI less with DES vs. BMS (p=0.11). –Death / MI less with 9-12 mo and >12 mo. of clopidogrel use compared to ≤ 9 mo (p < 0.001). Clopidogrel compliance by Rx records was 95% Kaiser Permanente

18. Conclusion Extended clopidogrel use ( >6 mo) from the index PCI was associated with less death / MI in both DES and BMS groups. Overall trend towards less death / MI in the DES group compared to the BMS group. Among clopidogrel non-users, no difference in death / MI by stent type. Kaiser Permanente