1 Contemporary PCI with the CYPHER ® Stent: The Standard of Care and Comparison David E. Kandzari, MD, FACC, FSCAI Chief Medical Officer Cordis Corporation

2Disclosure Employee:Cordis, Johnson & Johnson

3 Dedicated Trials with CYPHER ® Stent in Specific Patient/Lesion Types Single, De Novo Long Lesions Small Vessels DM MVD ISR CTO Bifurcations AMI Left Main Direct Stenting Stairway to Evidence-Based Medicine RAVEL, SIRIUS, REALITY, ENDEAVOR III DIRECT TYPHOON STRATEGY SESAMI MISSION PROSIT Park LL Park LL 2 SVELTE, SIRIUS 2.25 SES-SMART Pache, et al. ISAR-SMART 3 PORTO I DECODE SCORPIUS DIABETES, CARDIA* ISAR-DIABETES ACROSS* PRISON II TROPICAL SISR RIBS II ISAR-DESIRE ARTS-2 COMBAT* SIRIUS-BIF Nordic PCI Differing Complexity * Trials have not been presented/published Randomized Controlled Trial (RCT) vs. BMS, Brachytherapy, or POBA NON-RCT RCTs VS. DES SIRTAX, BASKET, and TAXi (All-Comers), Zhang, et al. E-SIRIUS, C-SIRIUS SCANDSTENT, CORPAL, Cervinka, et al. (high-risk) SVG RRISC 16 RCTs: SES vs. BMS N=5, RCTs SES vs. PES n = 7,917

4RAVEL*SIRIUS*C-SIRIUSE-SIRIUS Study Type Prospective, Multi-Center, Blinded, Randomized # of Patients 238 (120 CYPHER ®, 118 BMS) 1,058 (533 CYPHER ®, 525 BMS) 100 (50 CYPHER ®, 50 BMS) 352 (175 CYPHER ®, 177 BMS) Lesion Type Single de novo lesion in native coronary artery RVD  2.5 to  3.5 mm  2.5 to  3.0 mm Lesion Length Lesion had to be covered with a single 18 mm stent 15 to 30 mm in length coverable with 2 stents 15 to 32 mm in length coverable with 2 stents AspirinIndefinitely Clopidogrel or Ticlopidine 2 months 3 months 2 months Compliance to 4-year follow-up CYPHER ® – 94.2% BMS – 94.1% CYPHER ® – 96.8% BMS – 97.0% CYPHER ® – 98.0% BMS – 98.0% CYPHER ® – 97.1% BMS – 98.3% Patient-level Pooled Analysis of 4 RCTs *The 2 trials provided to support US indication: Improving coronary lumen diameter in patients with symptomatic ischemic disease due to discrete de novo lesions of ≤ 30 mm with a diameter of ≥ 2.5mm or ≤ 3.5mm.

5 Freedom From TLR Through 4 Years Freedom From TLR Time After Initial Procedure (days) Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials LR p<0.001  = 15.7% ®

6 Cumulative Incidence of Myocardial Infarction*: 0 – 1,440 Days (4 Years) # Entered 0 D 180 D 360 D (1 yr) 720 D (2 yr) 1080 D (3 yr) 1440 D (4 yr) Sirolimus Bx VELOCITY® % LR p=  (95% CI 0.2%[-2.2%, 2.6%]) Cumulative Incidence of MI Time After Initial Procedure (days) 6.4% Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials * Non –Q wave CK levels greater then 2 times normal with elevated CKMB ®

7 Cumulative Incidence of Death: 0 – 1,440 Days (4 Years) # Entered 0 D 180 D 360 D (1 yr) 720 D (2 yr) 1080 D (3 yr) 1440 D (4 yr) Sirolimus Bx VELOCITY® LR p=  (95% CI 1.4%[-1.0%, 3.7%]) Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials Cumulative Incidence of Death Time After Initial Procedure (days) 6.7% 5.4% ®

8 Cumulative Incidence of Stent Thrombosis to Latest Follow-up (4-5 Years, 4 Trials) SES1.2%BMS0.6% p-Value Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials Data between 4 and 5 years are from the RAVEL and SIRIUS Trials ProtocolBMSSESSES1.7%BMS1.9% p-Value 0.703SES4.1%BMS5.1% Definite or Probable ARC Any ARC SES1.4%BMS1.0% p-Value Definite ARC

9 Thrombosis Incidence Analysis: ARC Definite or Probable ARC Definite or Probable Stent Thrombosis (Days) SES (N=878 Patients) BMS (N=870 Patients) Acute Thrombosis (0-1) 0.0% (0/878) 0.0% (0/870) Sub-Acute Thrombosis (2-30) 0.4% (4/877) 0.3% (3/870) Late Thrombosis (31-360) 0.1% (1/874) 1.0% (8/865) Very Late Thrombosis ( ) 0.9% (8/848) 0.5% (4/843) Any Thrombosis (0-1440) 1.5% (13/848) 1.8% (15/843) Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials

10 Clinical Impact Following TLR and ARC (Definite/Probable) ST CYPHER ® Stent n = 878 BMS n = Deaths 13 MI 13 D/MI ST Deaths (n) MI (n) D/MI (n) 5 Deaths 13 MI 15 D/MI 5 Deaths 9 MI 13 D/MI 194 TLRs 15 ST Deaths (n) MI (n) D/MI (n) 3 C 2 NC 8 C 2 NC 5 C 2 NC Cardiac Death = C Non-Cardiac Death = NC 4-year Follow-up of 4 Key RCTs 3 Deaths 1 MI 4 D/MI 56 TLRs 1 C 2 NC

11 Meta-Analysis: Any MI up to 1 Year in SES vs. BMS RCTs 1 / / / / / / / 50 2 / 50 1 / 54 2 / 29 2 / / / / / / / 80 6 / 80 2 / / / / / 87 8 / 88 4 / / / / 95 5 / 95 9 / / Study name Model MH risk difference p-Value SESBMS Relative Weight (Fixed) Relative Weight Random MH risk difference and 95% CI RAVEL SIRIUS E-SIRIUS C-SIRIUS DECODE SES-SMART BASKET SCANDSTENT DIABETES PRISON II Pache STRATEGY TYPHOON SESAMI SCORPIUS MISSION Fixed Random Favors SES Favors BMS Q-Value Degree of freedom (Q) I2I2I2I2 p-Value Heterogeneity

12 Q-Value Degree of freedom (Q) I2I2I2I2 p-Value Heterogeneity Meta-Analysis: All Cause Mortality up to 1 Year in SES vs. BMS RCTs Study name Model MH risk difference p-Value SESBMS Relative Weight (Fixed) Relative Weight Random RAVEL SIRIUS E-SIRIUS C-SIRIUS DECODE SES-SMART BASKET SCANDSTENT DIABETES PRISON II Pache STRATEGY TYPHOON SESAMI SCORPIUS MISSION 2 / / / / / / / 50 0 / 54 2 / 29 0 / / / / / / / 80 0 / / / / 87 8 / 88 8 / / / / 95 4 / 95 2 / / Fixed Random MH risk difference and 95% CI Favors SES Favors BMS

13 Meta-Analysis: Thrombosis up to 1 Year in SES vs. BMS RCTs Study name Model MH risk difference p-Value SESBMS Relative Weight (Fixed) Relative Weight Random MH risk difference and 95% CI 0 / / / / / / / 50 0 / 54 0 / 29 1 / / / / / / / 80 2 / 80 2 / / / / / 87 2 / / / / / / / RAVEL SIRIUS E-SIRIUS C-SIRIUS DECODE SES-SMART BASKET SCANDSTENT DIABETES PRISON II Pache STRATEGY TYPHOON SESAMI MISSION Fixed Random Favors SES Favors BMS Q-Value Degree of freedom (Q) I2I2I2I2 p-Value Heterogeneity

14 TLR in Randomized Clinical Trials of CYPHER Stent vs. BMS Control n= (%) Patients PRISON 2 SES- SMART 1 year p=0.001  79% 8 months p=0.002  67% 1 year p<  79% 9 months p<0.001  80% (TVR) DIABETESDECODESCORPIUS 1 year p=0.043  62% 8 months p=0.002  75% TYPHOONSESAMI 1 year p<  71% 1 year p<0.05  62% STRATEGY 8 months p=0.006  72% MISSION 1 year p=0.005  72% BMS Control CYPHER ® Stent 4 RCTs: Leon M., et al., TCT 2005; Oral Presentation. PRISON 2: Suttorp MJ., et al., Circulation 2006;114: SES-SMART: Ardissino., JAMA 2004; 292: DIABETES: Sabaté M., et al., Circulation 2005;112: DECODE: Chan C., et al., AHA 2005; Oral Presentation. SCORPIUS: Baumgart D., et al., TCT 2006; Oral Presentation. TYPHOON: Spaulding C., et al., N Engl J Med 2006;355: SESAMI: Menichilli, M., et al., PCR 2006; Oral Presentation. STRATEGY: Vaglimigli M., et al., J Am Med Assoc 2005;293: MISSION: Jukema JW., AHA 2006, Oral Presentation. Diabetes*CTO* Small Vessels* AMI* 4 RCT Pooled

15SESPES OR (95% CI) CORPAL22/17735/ ( ) ISAR-DESIRE13/9120/ ( ) ISAR- Diabetes 7/10217/ ( ) REALITY88/89895/ ( ) SIRTAX23/34844/ ( ) TAXi--- Overall151/1,616211/1,613- Fixed Effects 0.68 ( ) Random Effects 0.67 ( ) Test for Heterogeneity: p=0.33 Test for Inconsistency: I 2 = 13% (95% CI, 0%-57%) Test for Overall Effect: p=0.001 Adapted from Kastrati, A., et al., JAMA 2005; 294: Odds Ratio (95% CI) Favors SES Favors PES Kastrati, et al., Meta-analysis of CYPHER vs. Taxus RCTs Significantly Lower Angiographic Restenosis with CYPHER

16 Risk Ratio Risk Ratio (95% CI) (95% CI) % Weight % Weight TAXi TAXi 2.94 ( 0.31, 27.80) 2.94 ( 0.31, 27.80) ISAR-DESIRE ISAR-DESIRE 0.42 ( 0.19, 0.92) 0.42 ( 0.19, 0.92) ISAR-DIABETES ISAR-DIABETES 0.53 ( 0.23, 1.21) 0.53 ( 0.23, 1.21) SIRTAX SIRTAX 0.55 ( 0.36, 0.86) 0.55 ( 0.36, 0.86) CORPAL CORPAL 0.64 ( 0.36, 1.11) 0.64 ( 0.36, 1.11) REALITY REALITY 0.96 ( 0.64, 1.44) 0.96 ( 0.64, 1.44) BASKET BASKET 0.50 ( 0.22, 1.14) 0.50 ( 0.22, 1.14) ISAR-SMART 3 ISAR-SMART ( 0.23, 0.80) 0.43 ( 0.23, 0.80) Zhang et al Zhang et al 0.73 ( 0.36, 1.45) 0.73 ( 0.36, 1.45) Long DES II Long DES II 0.32 ( 0.12, 0.86) 0.32 ( 0.12, 0.86) PROSIT PROSIT 0.33 ( 0.09, 1.19) 0.33 ( 0.09, 1.19) Overall Overall 0.59 ( 0.47, 0.74) 0.59 ( 0.47, 0.74), I 2 =16.1% Risk Ratio Risk Ratio Favours SES Favours SES Favours PES Favours PES SIRPACT Meta-analysis of CYPHER vs. Taxus RCTs Significantly Lower TLR with CYPHER Windecker S., et al., TCT 2005; Poster Presentation.

17 Source: A. Kastrati, FDA Panel Presentation, Washington, DC, December 2006 Kastrati, et al., Meta-analysis of CYPHER vs. Taxus RCTs Significantly Lower MACE with CYPHER N=5,074. Mean follow-up 25.1 months

18 A. Kastrati, FDA Panel Presentation, Washington, DC, December 2006 N=5,074. Mean follow-up 25.1 months Kastrati, et al., Meta-analysis of Cypher vs. Taxus RCTs Trend for Lower Death or MI with Cypher

19 Difference in TLR Rates vs. Average TLR for the CYPHER Stent vs. Taxus Stent * TVR rates TAXi SORT OUT II REALITY ISAR-DESIRE* ISAR-SMART 3 ISAR-DIABETES SIRTAX CORPAL BASKET* (TVR) PROSIT Long DES II. The difference between TLR rates for the CYPHER ® Stent and Taxus Stent in a given trial correlates with the average TLR for that trial. The higher the risk, the greater the difference in outcomes.  TLR (%) TLR (%)

20 OUS e-CYPHER US PMS e-CYPHER* D.E.S. COVER S.T.L.L.R. Japan- PMS J-CYPHER Study Type Open Enrollment Registry Angio eval: stent deployment on TVR Open Enrollment Registry Enrollment # of Patients 15,1572,0674,2351,5542,03214,087 # of Sites Location Countries 38 United States Japan41Japan Independent CEC YesYesYesYesYesYes Independent Data Mgmt YesYesYesYesYesYes Monitoring3%100%--100%3% Anti-platelet Medications ASA, Ticlopidine, Clopidogrel ASA, Ticlopidine Clinical Follow-up 1, 6, and 12 months Also yearly f/u to 5-years Worldwide Experience with CYPHER in Broad, Unselected Patient Populations * FDA mandated PMS

21 1-year F/U in 25,156 Patients - All Events CEC Adjudicated Stent Thrombosis Rates Across 6 Registries Early (0-30 Days) Late ( Days) n=15,157 n=2,067 n=4,235 n=1,554 n=8,349 n=2,032 n=8,349 n=2,032 (%) Patients NA Early + Late e-CYPHER (OUS) e-CYPHER (US PMS) J-CYPHERJ-PMSDEScoverSTLLR 1 yr F/U 88% 1 yr F/U 75% 1 yr F/U 89.6% 1 yr F/U 98% 1 yr F/U 93.6% 1 yr F/U 31% Interim Data Per Protocol ARC (Def/Prob)

Data represented as percent. Source: D. Baim, FDA Panel Presentation, December 8, 2006 accessed and Cordis InternalData Diabetes Lesion >28mm <2.5mm vessel diameter Multiple stents Multi- vessel ARRIVE 1/2 N=7,393 Primary ARC definite/probable ST 1-year primary ARC definite/probable stent thrombosis rates among high-risk subgroups from e-Cypher US and ARRIVE 1/2 Registries Diabetes Lesion >28mm <2.5mm vessel diameter Multiple stents Multi- vessel e-Cypher U.S. PMS N=2,067 Primary ARC definite/probable ST ‘Real world’ outcomes with Taxus or CYPHER Through 1 Year

23Diabetics All Comers Long-Term Myocardial Infarction Rates (> 1 Year) in CYPHER Stent Studies n= (%) Patients All- Comers Mod Risk BMS Control CYPHER ® Stent On-label (n=878) MVD Small Vessels ISR LM Taxus 2 years 3 years 1.8 y 4 y 5 y **** Valglimigli L, et al. JAMA 2005;293: REALITY: Morice MC, ESC 2006; Poster Presentation. SIRTAX: Windecker S, ESC 2006; Poster Presentation. de la Torre, et al., Rev Esp Cardiol 2006; 59: ISAR-SMART 3: Mehilla J., et al., AHA 2006; Oral Presentation. DIABETES, et al., ESC 2006; Oral Presentation. Kaiser Perm: TCT 2006; Oral Presentation. SES-SMART: ACC 2005; Oral Presentation. SVELTE: TCT 2006; Oral Presentation. TROPICAL: TCT 2006; Oral Presentation. RESEARCH: Daemen J., et al., Am J Cardiol 2006; 98: ARTS II: Serruys PW, et al., TCT 2006; Oral Presentation. 4 and 2 RCTs: Internal Data, Cordis Corporation. NCNCNC * RCTs NC = No Control ** 2,645 SES Patients Outside of 4 Key Trials with > 1 Year Follow-up Not Avail. In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on * The safety and effectiveness of the CYPHER® Stent in these sub-populations have not been established.

24Diabetics* All Comers (%) Patients All- Comers Mod Risk On-label (n=878) MVD* Small Vessels* ISR* LM 2 years 3 years 1.8 y 4 y 5 y 2,645 SES Patients Outside of 4 Key Trials with > 1 Year Follow-up BMS Control CYPHER ® Stent Taxus * RCTs NC = No Control n= Valglimigli L, et al. JAMA 2005;293: REALITY: Morice MC, ESC 2006; Poster Presentation. SIRTAX: Windecker S, ESC 2006; Poster Presentation. de la Torre, et al., Rev Esp Cardiol 2006; 59: ISAR-SMART 3: Mehilla J., et al., AHA 2006; Oral Presentation. DIABETES, et al., ESC 2006; Oral Presentation. Kaiser Perm: TCT 2006; Oral Presentation. SES-SMART: ACC 2005; Oral Presentation. SVELTE: TCT 2006; Oral Presentation. TROPICAL: TCT 2006; Oral Presentation. RESEARCH: Daemen J., et al., Am J Cardiol 2006; 98: ARTS II: Serruys PW, et al., TCT 2006; Oral Presentation. 4 and 2 RCTs: Internal Data, Cordis Corporation. **** Long-Term Mortality Rates (> 1 Year) in CYPHER ® Stent Studies NCNCNC ** In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on * The safety and effectiveness of the CYPHER® Stent in these sub-populations have not been established.

25 CYPHER Stent: Final Conclusions  The CYPHER stent has demonstrated clinically meaningful, sustained benefit in reducing the need for repeat revascularizations in a wide array of clinical settings and lesion complexities –Standard of care, standard for comparison  No difference in overall risk of stent thrombosis in 4 RCTs comparing CYPHER with BMS –No significant difference in death, and death or MI –Temporal distribution of stent thrombosis may vary between CYPHER Stent and BMS  Systematic overview of CYPHER vs. Taxus RCTs demonstrate significantly lower TLR and MACE in favor of the CYPHER Stent –Trend for lower death/MI (OR 95% CI: 0.86 [0.72, 1.02])

26 In high-risk patient subgroups, different risk: benefit ratio compared to 4 key CYPHER trials:  Benefit similar to lower risk groups: –Significant relative reductions in TLR/TVR of the CYPHER Stent: 62-80% vs. BMS62-80% vs. BMS 41-45% vs. PES41-45% vs. PES  Risk: –Rates of death, MI, or stent thrombosis numerically higher than on-label trials: No significant differences between the CYPHER Stent and BMSNo significant differences between the CYPHER Stent and BMS Elevated risk related to patient and lesion subgroupsElevated risk related to patient and lesion subgroups Some data suggest differential risk profile of SES vs. PESSome data suggest differential risk profile of SES vs. PES CYPHER Stent: Final Conclusions

27 Commitments to Interventional Community  Extend follow-up of 3 SIRIUS Trials to 8 years  Coordinate the extended follow-up of 10 RCTs (n=4,500 patients) to 5 years  Collaborate with regulatory agencies and professional societies to develop approval pathways for expanded indications  Enable Interventional Cardiologists to improve patient outcomes through new device design and clinical trials

28 Back-Up Slides

29 1-year RCTs DECODESCORPIUS P=NSP=NS 4-year post-hoc subgroup analyses DIABETESP=NS 2-year RCT Summary of Contemporary Diabetic Mortality Data n = *Lee T et al., Am J Cardiol, 2006; 98: DIABETES: Sabaté M., et al., ESC 2006; Oral Presentation. DECODE: Chan C., et al., AHA 2005; Oral Presentation. SCORPIUS: Baumgart D., et al., TCT 2006; Oral Presentation. 4 key RCTs CYPHER® Stent: Internal Data, Cordis Corporation. Letter from Don Baim, M.D. BMSSESPES % Patients P=NS 4 Key RCTs Taxus Stent P= Key RCTs CYPHER® Stent 5-year Follow-up of BMS Published Data *

30 Low Mortality in BMS arm of CYPHER Trials Four-Year Follow-up of Sirolimus-eluting Stents in Comparison with Bare Metal Stents: A Pooled Safety Analysis of the RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials in 1,748 Patients, Patrick Serruys, Erasmus Medical Center: Downloaded 01/05/2007: