1. Journal Club Julie Shah, MD Milton S Hershey Medical Center Penn State University

2. Disclosure ♥I do not have any financial interests with the manufacturer of the products discussed in this presentation

3. Objective ♥Analyze the most current journals regarding diabetes research

4. Differential Clinical Responses to Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents in Patients With and Without Diabetes Mellitus Gregg. W. Stone, Elvin Kedhi, Dean J. Kereiakes, Helen Parise, Martin Fahy, Patrick W. Serruys and Pieter C. Smits

5. Background ♥Drug eluting stents have significantly lower rates of target- lesion revascularization (TLR) and target- vessel revascularisation (TVR) compared to BMS in patients with and without Diabetes. ♥Prior studies have shown comparable rates of restenosis for Paclitaxel eluting stents in pts with/ without diabetes ♥Efficacy of rapamycin analog eluting stent ( everolimus, sirolimus etc) in pts with diabetes vs without remains unclear

6. Hypothesis ♥To evaluate any differences in safety outcomes between different DES according to the presence of diabetes. ♥To confirm better outcomes with use of Everolimus-eluting stent (EES) compared to Paclitaxel-eluting stent (PES) in pts without diabetes

7. This study has two parts ♥Comparison of outcomes in patients  without diabetes mellitus  With diabetes mellitus

8. Material & Methods ♥Data from four trials ♥Each study was prospective, randomized, single-blinded ♥Follow-up is planned for 5 years in each trial and is currently complete through 2years in all 4 studies

9. Meta-analysis with four major studies

10. Source of Funding ♥The SPIRIT II, III, and IV trials were funded by Abbott Vascular. ♥The COMPARE trial was funded by research grants from Abbott Vascular and Boston Scientific. ♥The analysis presented here was funded in part by a research grant from Abbott Vascular

11. Statistical Analysis ♥SAS version 9.1.3 ♥Intention to treat ♥Multivariate analyses with logistic regression ♥Chi square, Fisher exact test and t- test ♥Kaplan-meier display ♥P value less than 0.05 was considered statistically significant

12. Results Total N=6780 Without Diabetes n=4911 (72.4%) EES (n= 3056) PES (n= 1855) Diabetes n=1869 (27.6%) EES (n= 1188) PES (n=681)

13. Results

17. Pts without Diabetes

18. Pts with Diabetes

22. Summary The major findings from this analysis are: ♥In pts without diabetes, EES has better outcomes ♥In pts with diabetes, there are no differences in outcomes ♥In diabetics not requiring insulin, ischemic TLR in reduced with EES ♥In diabetics requiring insulin, ischemic TLR is less with PES

23. Discussion ♥Difference in outcome based on diabetes status may be related to difference in mechanism of action of these two drugs ♥Paclitaxel disrupts microtubular function and interferes with multiple pathways of restenosis- smooth muscle proliferation, migration, matrix production, cell to cell signaling

24. Mechanism of Everolimus ♥Rapamycin analogs interfere with cellular mitosis. They bind to FK binding protein and modulate the activity of mTOR ( mammalian target of rapamycin) which results in cell cycle arrest. ♥These processes tightly regulated by glycosylation- dependent enzymes, and thus diabetes may be playing a role in the their function

25. Limitations ♥the sample size remains inadequate to exclude small differences between the 2 stent types in t he diabetic cohort ♥a very large randomized trial (5000 patients) restricted to patients with diabetes mellitus would berequired to determine whether meaningful differences in safety outcomes between EES and PES he diabetic cohort ♥Longer-term follow-up is necessary to deter-mine whether meaningful differences between the stent types in diabetic patients will emerge over time

26. The End