1. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction in Massachusetts Laura Mauri, Treacy S. Silbaugh, Robert E. Wolf, Katya Zelevinsky, Ann Lovett, Manu Varma, and Sharon-Lise T. Normand Brigham and Women’s Hospital, Harvard Medical School, Harvard School of Public Health all in Boston, Massachusetts March 30, 2008 American College of Cardiology, Chicago

2. Disclosure Information Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction in Massachusetts The following relationships exist related to this presentation: L MauriHonoraria:Abbott, Boston Scientific, Cordis, Medtronic Modest Level T Silbaugh, R Wolf, K Zelevinsky, A Lovett, and SL Normand: Salary and research funding from Massachusetts Department of Public Health M VarmaNo disclosures

3. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction We wish to thank Paul Dreyer, Ph.D. of the Massachusetts Department of Public Health and the members of the Mass-DAC PCI Data Adjudication Committee Josh Krasnow, M.D. Anthony Marks, M.D. Theo E. Meyer, M.D., Ph.D. Kathy Minahan, R.N. Zoran Nedelijkovic, M.D. Barbara Oxley, R.N. Thomas C. Piemonte, M.D. Kenneth Rosenfield, M.D. Pinak B. Shah, M.D. Samuel J. Shubrooks Jr., M.D. James Waters, M.D. Bonnie Weiner, M.D. Kurt Barringhaus, M.D. Clifford J. Berger, M.D. David Cohen, M.D. Angela Corey, R.N. Jean Crossman, R.N. Daniel Fisher, M.D. Joe Garasic, M.D. Jean-Pierre Geagea, M.D. Gregory Giugliano, M.D. Kalon Ho, M.D. Alice Jacobs, M.D. James Kirshenbaum, M.D.

4. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Background Acute myocardial infarction represents a large proportion of stenting procedures, and is the clinical syndrome with the greatest documented benefit for PCI Yet patients with acute myocardial infarction (AMI) have not been included in the major randomized trials comparing drug eluting stents (DES) to bare metal stents (BMS) And specific studies of AMI have been limited in size and study duration to detect adverse clinical events.

5. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Objectives – To evaluate whether the use of DES is associated with increased rates of death or MI compared with BMS in patients with acute myocardial infarction – To evaluate whether the use of DES is associated with reduction in revascularization compared with BMS in patients with acute myocardial infarction

6. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Methods: All PCI for NSTEMI or STEMI in Massachusetts non-federal hospitals April 2003 – Sept. 30, 2004 Clinical and procedural factors collected prospectively using ACC NCDR instrument and reported to Mass-DAC (State Dept of Public Health database) Mortality from hospital record, MA Registry of Vital Records & Statistics, & Social Security website Myocardial infarction and revascularization from Mass-DAC PCI and CABG data merged with hospital discharge data Non-Massachusetts residents excluded

7. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Methods Patients assigned to DES or BMS groups based on treatment at index procedure Patients treated with both types were excluded Propensity score matching – Logistic regression to predict DES treatment by up to 63 patient, procedural, hospital variables – 1:1 caliper matching of DES to BMS patients Primary outcomes: Matched risk differences for mortality, myocardial infarction and revascularization rates at 2 years Paired t-test, 2-sided alpha 0.05

8. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction N=21,019 PCI Patients in Massachusetts April 1, 2003- September 30, 2004 Complete 2 year follow-up N=21,019 PCI Patients in Massachusetts April 1, 2003- September 30, 2004 Complete 2 year follow-up 575 non-residents excluded 183 administrative files not linkable N=8,454 MI Patients N=8,454 MI Patients (40%) N=4,016 DES Only Patients N=4,016 N=3,200 BMS Only Patients N=3,200 480 patients with both stent types excluded N=7,696 Patients 12,565 non-MI PCI patients 28% PES 72% SES

9. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Patient Characteristics before Match DES (n = 4016) BMS (n =3200) p value Age – yrs 63.6 ±13.4 64.3 ±13.9 0.04 Female (%) 33.033.00.91 Diabetes Mellitus (%) 25.622.60.004 Hyperlipidemia (%) 66.762.2<0.001 Hypertension (%) 69.065.1<0.001 Current Smoker (%) 29.031.30.03 Prior PCI (%) 14.012.80.13 Prior MI (%) 22.323.30.33 Prior CABG (%) 8.39.80.004

10. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Patient Characteristics before Match DES (n = 4016) BMS (n =3200) p value Congestive Heart Failure (%) 9.410.50.11 Chronic Lung Disease (%) 11.112.00.24 History of Neoplasm (%) 2.23.00.02 History of GI Bleeding (%) 2.43.20.05 Chronic Renal Insufficiency (%) 6.16.70.30 Dialysis (%) 1.61.30.21 Clopidogrel Pretreatment (%)* 34.932.30.02 GPIIb/IIIa Inhibitor Pretreatment (%) 35.138.20.007 4/03- 9/04) consensus recommendations were for 1m DAP for BMS and 3-6m for DES. *Although dual antiplatelet therapy (DAP) compliance data are not available, during the time period of entry to the study (4/03- 9/04) consensus recommendations were for 1m DAP for BMS and 3-6m for DES.

11. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Procedure Indications before Match DES (n = 4016) BMS (n =3200) p value MI type <0.001 STEMI STEMI38.956.8 NSTEMI NSTEMI61.143.2 Procedure status <0.001 Urgent (%) Urgent (%)47.535.4 Emergency/Salvage (%) Emergency/Salvage (%)37.554.2 Thrombectomy7.813.8<0.001

12. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Procedural Characteristics before Match DES (n = 4016) BMS (n =3200) p value Number of vessels treated 1.18 ± 0.43 1.10 ± 0.32 <0.001 Number of lesions treated 1.41 ± 0.70 1.31 ± 0.60 <0.001 Left anterior descending (%) Left anterior descending (%)43.737.0<0.001 Circumflex (%) Circumflex (%)32.926.0<0.001 Right coronary (%) Right coronary (%)39.845.8<0.001 Left main (%) Left main (%)1.51.20.32 Saphenous vein graft (%) Saphenous vein graft (%)3.76.1<0.001 Arterial graft (%) Arterial graft (%)0.10.20.72

13. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction N=4,016 patients with DES for MI N=4,016 patients with DES for MI N=3,200 patients with BMS for MI N=3,200 patients with BMS for MI 2,453 (61.1%) DES for NSTEMI 2,453 (61.1%) DES for NSTEMI 1,563 (38.9%) DES for STEMI 1,563 (38.9%) DES for STEMI 1,382 (43.2%) BMS for NSTEMI BMS for NSTEMI 1,382 (43.2%) BMS for NSTEMI BMS for NSTEMI 1,818 (56.8%) BMS for STEMI 1,818 (56.8%) BMS for STEMI Propensity score matched pairs 2629 MI 1,221 NSTEMI 1,302 STEMI 1,221 NSTEMI 1,302 STEMI 2629 MI matched pairs

14. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Patient Characteristics after Match DES (n = 2629) BMS (n =2629) % SD Age – yrs 64.764.20.0 Female (%) 33.733.40.8 Diabetes Mellitus (%) 22.422.9-1.3 Hyperlipidemia (%) 62.163.6-3.2 Hypertension (%) 66.166.7-1.3 Current Smoker (%) 31.030.80.3 Prior PCI (%) 12.612.8-0.9 Prior MI (%) 24.023.02.4 Prior CABG (%) 9.08.80.5 *%SD = Percent Standardized Difference Values <10% reflect well-matched characteristics

15. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Patient Characteristics after Match DES (n = 2629) BMS (n =2629) %SD Congestive Heart Failure (NYHA 3-4) 9.28.33.1 Chronic Lung Disease (%) 12.912.02.9 History of Neoplasm (%) 2.92.71.4 History of GI Bleeding (%) 3.23.20.2 Chronic Renal Insufficiency (%) 6.66.50.3 Dialysis (%) 1.41.5 Clopidogrel Preadminstered (%) 29.631.2-3.5 GPIIb/IIIa Inhibitor Preadminstered (%) 38.837.72.4 *%SD = Percent Standardized Difference Values <10% reflect well-matched characteristics

16. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Procedure Indications after Match DES (n = 2629) BMS (n =2629) MI type STEMI STEMI55.450.5 NSTEMI NSTEMI44.649.5 Procedure status Urgent (%) Urgent (%)37.640.2 Emergency/Salvage (%) Emergency/Salvage (%)51.847.8 Thrombectomy9.18.8

17. Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction Procedural Characteristics after Match DES (n = 2629) BMS (n =2629) %SD Multilesion treatment 2 lesions 2 lesions20.021.3-3.3 3 lesions 3 lesions3.74.7-4.9 4 lesions 4 lesions0.70.8-1.8 Target vessel Target vessel Left circumflex Left circumflex26.428.2-3.9 Right coronary Right coronary44.843.62.5 Left main Left main1.51.41.0 Saphenous vein graft Saphenous vein graft5.15.00.5 Arterial graft Arterial graft0.20.20.0 *%SD = Percent Standardized Difference Values <10% reflect well-matched characteristics

18. Drug-Eluting & Bare Metal Stenting in Massachusetts Risk Differences in Matched MI Patient Groups at 2 years Risk Difference (95% CI), DES v. BMS Death Recurrent MI NSTEMI MI STEMI n=2629 pairs n=1221 pairs n=1302 pairs Favors DES Favors BMS -2.7% [-4.5%, 0%] P=0.002 -1.9% [-4.6%, 0.9%] P=0.18 -3.1% [-5.4%, -0.8%] P=0.009 Favors DES Favors BMS -1.5% [-3.1%, 0.2%] P=0.08 -2.4% [-5.0%, 0.3%] P=0.07 -1.6% [-3.7%, 0.5%] P=0.127

19. Drug-Eluting & Bare Metal Stenting in Massachusetts Risk Differences in Matched MI Patient Groups at 2 years Risk Difference (95% CI), DES v. BMS RevascularizationTVR Favors DES Favors BMS -5.3% [-7.4%, -3.2%] P<0.001 -5.3% [-8.4%, -2.3%] P<0.001 -6.0% [-9.0%, -3.0%] P<0.001 Favors DES Favors BMS -3.6% [-5.2%, -2.0%] P<0.001 -2.9% [-5.4%, -0.5%] P=0.02 -3.5% [-5.8%, -1.3%] P=0.002 NSTEMI MI STEMI n=2629 pairs n=1221 pairs n=1302 pairs

20. Drug-Eluting & Bare Metal Stenting in Massachusetts 2-Year Outcome in Matched MI Patients 23732431251226142629BMS 24332484255026182629DES 730365180300No. at Risk 21922285243025922629BMS 22832368248326042629DES 730365180300 030180365730DES26292624242722432127 BMS26292618237220911957 030180365730DES26292624249223802291 BMS26292618244322502148 Death Recurrent MI RevascTVR BMS DES

21. Drug-Eluting and Bare Metal Stenting for MI in Massachusetts Sensitivity analyses Match adjusting for time on market yields consistent conclusions STEMI group exclusion of programs without surgery on site, or patients with >24h presentation, yields consistent conclusions No evidence of a 2 day clinical or statistical significant benefit which is supportive of no residual confounding 2 day mortality DES-BMS  = -0.5% [-1.0,+0.04] 2 year mortality DES-BMS  = -2.7% [-4.5%, 0%]

22. Complete 2 year data are available for 7216 unique DES or BMS procedures for MI in Massachusetts from April 2003- September 2004. Propensity matched analysis of 5258 patients with MI demonstrated: No increase in rates of death, or myocardial infarction associated with DES as compared to BMS use at 2 years overall and for the subsets of STEMI and NSTEMI – Although our aim was to detect a signal of harm, we observed lower 2y mortality in STEMI patients treated with DES A lower rate of repeat revascularization in patients treated with DES compared with BMS overall and for both subsets. Drug-Eluting and Bare Metal Stenting in Massachusetts Conclusions