Final Clinical and Angiographic Results From a Nationwide Registry of FIREBIRD Sirolimus- Eluting Stent: Firebird In China (FIC) Registry (PI R. Gao)

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1 The Microport FIREBIRD Polymer-based Sirolimus- Eluting Stent Clinical Trial Program Update: The FIC and FIREMAN Registries Junbo Ge, MD, FACC, FESC, FSCAI On behalf of Runlin Gao (FIC PI) and Haichang Wang (FIREMAN PI)

2 Final Clinical and Angiographic Results From a Nationwide Registry of FIREBIRD Sirolimus- Eluting Stent: Firebird In China (FIC) Registry (PI R. Gao) A Prospective Multicenter Study to Evaluate Long Term Efficacy and Safety of the FIREBIRD Sirolimus Eluting Stent in Patients with CoMplex CoronAry LesioNs(FIREMAN) (PI H. Wang)

3 Disclosure Statement of Financial Interest I, (Junbo Ge) DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

4 Aim of the FIC Post-marketing surveillance registry to determine: Safety and efficacy of FIREBIRD SES in routine clinical practice in Chinese population Aim of the FIREMAN To evaluate the long term efficacy, safety and angiographic outcomes of FIREBIRD Sirolimus-eluting stent for the treatment of complex coronary lesions (off-label use)

5 Study Design(FIC) All patients receiving >= 1 Firebird SES are enrolled after informed consent was signed Patients implanted other stents and had previous MI within 1 week are excluded Clinical FU at 30-day, 6- and 12-month Target recruitment = 1500 patients Angiographic follow-up at 9 months for 50% enrolled patients

6 Pre-defined Objectives(FIC) Primary MACE (Cardiac death, nonfatal MI, and target lesion 12-month Secondary In-stent and in-segment binary Restenosis rates, late 9-month

7 Patient Enrollment (FIC) patients August 64 September October November 646 December 1138 January 1569 First patient in Jul. 13, 2005 Last patient in Jan. 31, 2006

8 Study Flow - Clinical (FIC) De-registered* (n=8) Enrolment, n=1569 Study population, n= days FU, n=1553 (99.5%) 12 months FU, n=1426 (91.4%) * non-studied stent (n=5), AMI patients (n=3)

9 Baseline Demographics (FIC) Patients 1561 Age (yrs) 62.3± ~88 Male 70.5% 1101/1561 Prior MI 31.4% 490/1561 Prior PCI 16.8% 262/1561 Prior CABG 2.0% 31/1561 Diabetes 24.2% 378/1561 -IRDM 13.2% 50/378 Hypertension 62.3% 973/1561 Hyperlipidemia 30.4% 474/1561 Positive Family History 6.9% 108/1561 Current Smoker 37.6% 587/1561 Unstable Angina 70.0% 1092/1561

10 Target Lesion Distribution (FIC) Target Vessel LM LAD LCx RCA Graft

11 ACC/AHA Lesion Classification (FIC) 44.8% n=1045 n=164 n= % 18.2% A B1 B2 C 30.0% n=698

12 Lesion Characteristics (FIC) Target Lesion (n=2330) Target lesions per patient, n 1.49 De Novo, n (%) 2240 (96.1) In-stent restenotic lesion, n (%) 69 (3.0) Total occlusion, n (%) 281 (12.1) Ostial lesion, n (%) 385 (16.5) Bifurcation, n (%) 316 (13.6) Moderate to severe angle, n (%) 160 (6.9) Reference Vessel Diameter by visual estimation, mm 2.97±0.43 Lesion length by visual estimation, mm 24.9±15.3 Diameter by visual estimation, % 86.3±10.5

13 Procedural Results (FIC) Target lesion, n=2330 Direct stenting, n (%) 701 (30.1) Length of stent, mm 29.2±15.4 Stents overlapping, n (%) 489 (21.0) Stents post-dilatation, n (%) 537 (23.1) Bifurcation treated by 2 stents, n (%) 58 (18.4) Residual stenosis by visual estimation, % 1.0±6.3 Dissection during procedure, n (%) 24 (1.0) Thrombosis during procedure, n (%) 14 (0.6) Procedural success per lesion, n (%) 2327 (99.9) Procedural success per patient, n (%) 1558 (99.8)

14 Cumulative 30-day Clinical Outcomes (FIC) n= N=1553 (99.5%), 100% monitoring n= n= n= n= n= cardiac death Non- Cardiac Death Q AMI NQ AMI TLR PCI TLR CABG MACE

15 Cumulative 12-month Clinical Outcomes (FIC) n= cardiac death N=1426 (91.4%), 100% monitoring n= Non- Cardiac Death n= n= n= n= Q AMI NQ AMI TLR PCI TLR CABG n= MACE

16 MACE-free Survival at 12-month (FIC)

17 Stent Thrombosis (FIC) 0.56%, n=8, SIRIUS definition %, n=14, ARC definition Thrombosis events Thrombosis events 1 Acute Sub-acute Late Definite/Confirmed Probable Possible

18 QCA at Baseline, n=585 (FIC) Mean±SD Median [Q1, Q3] Pre-procedure Reference vessel diameter, mm 2.68± [2.40, 2.99] Lesion length, mm 23.5± [12.7, 28.3] Diameter stenosis, % 72.1± [61.0, 79.0] Minimal lumen diameter, mm 0.75± [0.55, 1.04] Post-procedure Diameter stenosis, % In-stent 17.2± [14.0, 20.0] In-segment 21.8± [16.0, 26.0] Minimal lumen diameter, mm In-stent 2.51± [2.22, 2.75] In-segment 2.30± [1.99, 2.58] Acute gain, mm In-stent 1.76± [1.42, 2.02] In-segment 1.44± [1.11, 1.75] Stent/lesion length ratio 1.40± [1.19, 1.49]

19 QCA at 9-month Angiographic Follow-up, n=585 (FIC) Diameter stenosis, % Mean±SD Median [Q1, Q3] In-stent 20.9± [15.0, 23.0] In-segment 25.2± [18.0, 29.0] Minimal lumen diameter, mm In-stent 2.38± [2.09, 2.65] In-segment 2.19± [1.89, 2.51] Late lumen loss, mm In-stent 0.14± [0.02, 0.16] In-segment 0.11± [-0.01, 0.14] Follow-up duration: 252±89 days

20 Binary Restenosis, n=585 (FIC) In-stent In-segment Binary Restenosis Rate, %

21 FIC Compared with China CYPHER Select Registry FIC, n=1561 CCSR, n=893* Reference vessel diameter, mm 2.68± ±0.42 Lesion length, mm 23.5± ±11.3 Diabetes mellitus, % Cumulative MACE at 1-year, % Cumulative cardiac death at 1-year, % Cumulative AMI at 1-year, % Cumulative TLR at 1-year, % In-stent late lumen loss,mm 0.14± ±0.39 In-segment binary restenosis rate, % * In CCSR (n=1189) study, 893 patients (75%) were treated by CYPHER Select stent exclusively

22 Baseline Firebird 2.5/23mm+3.0/23mm Case 3 Firebird 3.0/33mm 2

23 Angiographic follow-up Case 3

24 Conclusions (FIC) The registry enrolled patients with more complex lesions and multiple vessel disease which reflected daily clinical practice The procedural success rate is high (99.8%) At 12-month, cumulative cardiac death (0.84%), MI (1.12%), TLR (1.82%), MACE (3.58%), and thrombosis rate (0.56% with SIRIUS definition and 0.98% with ARC definition) are acceptable QCA revealed in-stent late loss 0.14±0.24mm, binary restenosis rates: in-stent 3.6%, in-segment 5.3% The safety and efficacy profiles of FIREBIRD SES are very similar to the results from China CYPHER Select Registry

25 EVENT Registry: DES increase Adverse Event Rates in off-label indications? Win HK et al. JAMA 2007;297:2001-9

26 A View from Emerging Markets: DES Penetration, Local Products, Operator Techniques and Tendencies in China

27 Off-label use by FDA of U.S. Definition of Complex Coronary Lesions by Protocol More complex and unapproved indications Very small vessels Very long lesions Chronic total occlusions Bifurcations Left main disease In-stent restenosis Multivessel disease Does Domestic DES increase adverse events in a more complex settings? Ostial Saphenous lesions vein grafts Severe Acute myocardial calcification infarction or angulation lesions

28 Study Algorithm(FIREMAN) Clinical follow-up Patient enrollment ( ) n = pts Enrolled 30 days 99.7% (1026/1029 pts) 6 months 98.7% (1016/1029 pts) 12months 97.2% (1000/1029 pts) Excluded pts due to hybrid stenting, n=49 (4.5%) Angiographic follow-up 8 months 51% (517/1013pts) Primary End Point : MACE at 12 months Secondary End Point:Binary Restenosis, Late loss at 8months, TVR, Stent thrombosis, Stroke at 12 months

29 Enrollment Information (FIREMAN) Sep Oct- 06 Nov Dec Jan- 07 Feb- 07 Mar- 07 Apr May- 07 Jun Jul- 07

30 Baseline Demographics (FIREMAN) Parameters n=1029 Age (years) 64.2±10.2 Male, n (%) 757 (73.57) Risk Factors CAD Family history, n (%) 107 (10.40) Pre-MI, n (%) 245 (26.20) Pre-PTCA, n (%) 166 (17.75) Hypercholesterimia, n (%) 192 (20.60) Hypertension, n (%) 669 (71.55) Smoking, n (%) 301 (32.26) Diabetes Mellitus, n (%) 235 (25.16) Insulin requiring, n (%) 171 (81.82) Non-insulin requiring, n (%) 38 (18.18) PCI Indications Silent ischemia, n (%) 10 (1.00) stable angina, n (%) 191 (19.00) unstable angina, n (%) 716 (71.24)

31 % Frequency of Complex Coronary Lesions Criteria* (FIREMAN) Mul t i - vessel CTO Smal l vessel Unprotected left mai n di sease Rest enosi s Total Target Lesions n= Long l esi on Os t i al Bi f ur cat i on Sever e angul at i on 2.74 * Criteria are not mutually exclusive.

32 Percentage of Patients Implanted With Different Number of Stents Percentage of Patients Implanted With Different Number of Stents % % 6.6 Numbers of stents per patient Total stents implanted n=2261 Mean stents implanted n=

33 Baseline QCA Results (FIREMAN) 1678 lesions in 1013 pts analyzed Pre-procedure In-stent In-segment Lesion length, mm 23.7± Reference vessel diameter, mm 2.63± Diameter stenosis, % 76.2± Minimal lumen diameter, mm 0.64± Post-procedure Reference vessel diameter, mm 3.04± Diameter stenosis, % 17.5± ±4.7 Minimal lumen diameter, mm 2.33± ±0.39 Acute gain, mm 1.69± ±0.45

34 8-month QCA Results (FIREMAN) 874 Lesions in 517 pts(51%) analyzed In-stent In-segment Reference vessel diameter, mm 2.97± Diameter stenosis, % 23.3± ±13.1 Minimal lumen diameter, mm 2.11± ±0.54 Late lumen loss, mm 0.21± ±0.36 Binary restenosis rate, % (n) 4.3 (38) 5.7 (50)

35 Angiographic Binary Restenosis (FIREMAN) 874 Lesions in 517 pts(51%) analyzed % 4.3 Binary Restenosis Rate In-Stent Proximal Edge Distal Edge In-Segment N=38 N=7 N=13 N=50

36 Clinical Events Up to 1-Year* (FIREMAN) 30 days 6 months 12 months MACE (%) 11 (1.1) 16 (1.6) 52 (5.1) Cardiac death (%) 2 (0.2) 5 (0.5) 6 (0.6) Non-fatal MI (%) 9 (0.9) 10 (1.0) 11 (1.1) TLR (%) 1 (0.1) 3 (0.3) 35 (3.4) TVR (%) 2 (0.2) 5 (0.5) 42 (4.1) Stent Thrombosis (%) 6 (0.6) 9 (0.9) 13 (1.3) Non-cardiac death (%) 1 (0.1) 3 (0.3) 9 (0.9) * unadjusted data

37 Clinical Events Up to 1-Year* (FIREMAN) % d 6months 12months Cardiac Death Nonfatal MI TLR MACE * unadjusted data

38 MACE/TLR-free Survival at 12 months (FIREMAN) MACE-free Survival Rate 94.2% TLR-free Survival Rate 97.9% DAY DAY

39 Cardiac death/non-fatal MI-free Survival at 12 months (FIREMAN) Cardiac Death-free Survival 99.4% Non-fatal MI-free Survival % 400 DAY DAY

40 1-Year Safety of Off-label Indications Stent Thrombosis Stent Thrombosis ARC Definite Stent thrombosis-free Rate(%) ARC ARC Total Probable Possible Acute( 24h) (0.19%) Subacute(24h-30d) (0.39%) Late (30d-1y) (0.68%) Total 5(0.48%) 6(0.58%) 2(0.19%) 13 (1.26%) DAY 98.7%

41 Dual Antiplatelet Treatment medication with Clopidogrel and ASA (%) Clopidogrel Asprin ds 6months 12months follow-up times

42 Predictors of Cumulative Stent Thrombosis By Cox Regression Analysis Parameters HR(95%CI) P value Male 0.187(0.021~1.658) Age 1.028(0.826~1.281) Pre-MI 2.659(0.698~10.130) Pre-PCI 1.114(0.193~6.434) Hypercholesterima 0.572(0.110~2.980) hypertension 1.026(0.302~3.490) Diabetes 6.852(2.091~22.453) Multi-vessel (0.127~2.226) Diffuse long 1.826(0.453~7.360) Small vessel 4.844(1.198~19.594) CTO 4.154(1.138~15.166) Bifurcation 0.800(0.053~12.025) Ostial 0.893(0.058~13.665) Severe angulation 0.001(0.000~ ) LM 0.001(0.000~ ) Restenosis 1.719(0.139~21.278) 0.673

43 Conclusions (FIREMAN) One-year outcomes showed that FIREBIRD SES was effective and safe even in a selectively complex lesion settings. FIREBIRD SES was effective in reducing restenosis, similar to the results from pivotal DES trials. Off label FIREBIRD SES use was not associated with increased rates of stent thrombosis, similar to other global studies on stent safety. Diabetes, small vessel and CTO were the predictors of stent thrombosis at one year.

44 Summary The two registries of Microport Firbird stent showed FIREBIRD SES was effective and safe in real world PCI even in a selectively complex lesion settings. FIREBIRD SES was effective in reducing restenosis, similar to the results from pivotal DES trials. Off label FIREBIRD SES use was not associated with increased rates of stent thrombosis, similar to other global studies on stent safety. Diabetes, small vessel and CTO were the predictors of stent thrombosis at one year. Long-term (>1 yr) safety were expected for further investigations.