Toshiya Muramatsu, MDKawasaki social Insurance Hospital, Kawasaki, Japan

The Japanese ASPARAGUSASPARAGUS Trial

ASPirAtion of LibeRated Debris in Acute MI

with GUardWire Plus TM System

•

•GIK•Nicorandil•Adenosine (pre-cond)•Na+/H+ pump inhib.•IIb/IIIa inhibitors

•

•IIb/IIIa inhibitors•Nicorandil•Adenosine (vaso-dil)•Adhesion antagonists (a-CD18)•Complement inhibitors•P-selectin inhibitors

Reperfusion of the IRA to the MyocardiumTherapeutic Targets and Agents

•Aqueous O2

•Hypothermia•Combination pharmacotherapy

•PTCA/Stents•Adjunct Anti-thrombotics

•Facilitated PCIMod from OMod from O’’Neill and GershNeill and Gersh

Myocardial Salvage

MicrocirculationEpicardial Flow

•Filters•Thromboembectomy

Investigator SiteToshiya Toshiya MuramatsuMuramatsu, MD Kawasaki social Insurance Hospital, MD Kawasaki social Insurance Hospital

Satoru Satoru SuwaSuwa, MD , MD JyuntendoJyuntendo Univ. Univ. IzuIzu--NagaokaNagaoka HospitalHospital

NaoyaNaoya Fujita, MD Eastern Japan Medical CenterFujita, MD Eastern Japan Medical Center

Shiho Koyama, MD Shiho Koyama, MD Saiseikai NoeSaiseikai Noe HospitalHospital

Masahiko Saito, MDMasahiko Saito, MD AgeoAgeo Central General HospitalCentral General Hospital

HaruoHaruo KamiyaKamiya, MD First Nagoya Red Cross Hospital, MD First Nagoya Red Cross Hospital

Akitsugu OidaAkitsugu Oida, MD , MD DokkyoDokkyo University CardiologyUniversity Cardiology

Takeshi Tsuchiya, MD Kanazawa Cardiovascular HospitaTakeshi Tsuchiya, MD Kanazawa Cardiovascular Hospitall

YuhkiYuhki HoritaHorita, MD Ishikawa , MD Ishikawa PrefecturalPrefectural Central HospitaCentral Hospital l

Shigeo Kawano, MD Shigeo Kawano, MD SakurabashiSakurabashi Watanabe HospitalWatanabe Hospital

Top 10 Enrollers

Total 341 cases randomized at 22 centers

Trial OrganizationPrincipal Investigator: Toshiya Muramatsu, MD

Kawasaki Social Insurance Hospital

Co-Principal Investigators: Kinzo Ueda, MDKoseikai Takeda Hospital

Masato Nakamura, MDToho University, Ohashi Hospital

QCA Core Lab: Ken Kozuma, MDCardio Core Japan

QCU Core Lab: Yoshiaki Ito, MDKawasaki Social Insurance Hospital

Data Management Core Lab: Hideki Hashimoto, MDCardio Core Japan

STEMISTEMI

Informed ConsentInformed Consent

CAGCAG

RandomizationRandomization

PCI (PCI (stentingstenting) ) with with PercuSurgePercuSurge

LVGLVG

PCI (PCI (stentingstenting) ) without protectionwithout protection

LVGLVG

180180--day FU (day FU (angioangio, clinical), clinical)

Trial Design Eligible for this study>18 yrs<12hrs from onsetculprit LAD, LCx, RCA

Exclusion criteriaLMT diseaseref diameter < 2.5 mmCardio pulmonary arrest

180180--day FU (day FU (angioangio, clinical), clinical)

14~3014~30--day FU (day FU (angioangio, clinical), clinical) 14~3014~30--day FU (day FU (angioangio, clinical), clinical)

Primary EndpointsFinal myocardial perfusion after primary PCI

TIMI flowCTFCBlush score

Myocardial damageCK, CK-MB, Troponin TST resolutionLVEF, LVEDV

Secondary Endpoints

Rate of complications related to protection deviceMACE at 6 months

Patient Enrollmentn=341

30-day F/Un=289

6 month F/Un= 328

Cardiac DeathProtected: 3Unprotected: 5Non-Cardiac DeathProtected: 2Unprotected: 3

Cardiac DeathProtected: 4Unprotected: 1Non-Cardiac DeathProtected: 2Unprotected: 3UnknownProtected: 8Unprotected: 8

Clinical Only

Protected Unprotected29 (16.8%) 24 (14.3%)

Clinical Only

Protected Unprotected29 (16.8%) 24 (14.3%)

Angiographic and Clinical

Protected Unprotected125 (72.3%) 124 (73.8%)

Angiographic and Clinical

Protected Unprotected125 (72.3%) 124 (73.8%)

Patient Flow

Protected Unprotected p value

Age, yearsAge, years 63.5 63.5 ±± 12.312.3 64.7 64.7 ±±11.111.1 NSNSMale, %Male, % 78.678.6 72.972.9 NSNSHypertension, %Hypertension, % 42.242.2 44.144.1 NSNSHyperlipidemiaHyperlipidemia, %, % 32.932.9 32.932.9 NSNSDiabetes, %Diabetes, % 31.831.8 32.332.3 NS NS Smoking, %Smoking, % 51.451.4 49.449.4 NSNSFamily history, %Family history, % 4.64.6 4.14.1 NSNSHistory of MI, %History of MI, % 1.71.7 2.92.9 NSNSKillipKillip class II class II –– IV, %IV, % 2.32.3 0.00.0 NSNSChest pain to Hosp., hrsChest pain to Hosp., hrs 4.2 4.2 ±± 2.82.8 4.4 4.4 ±± 3.43.4 NSNSCK at ER, IU/dlCK at ER, IU/dl 589589 569569 NSNSCKCK--MB at ERMB at ER 4646 4545 NSNS

Patient Demographics

((n=165)n=165) ((n=164)n=164)

Protected Unprotected pvalue

Vessel disease, %1 59 58 NS2 32 27 NS3 9 15 NS

Target vessel, %RCA 40 42 NSLAD 50 48 NSLCx 10 10 NS

Pre TIMI flow0 44 44 NS1 17 14 NS2 21 19 NS3 5 11 NS

Lesion Demographics((n=165)n=165) ((n=164)n=164)

Protection Unprotected pvalue

Procedural success, % 98.9 97.1 NS

Vascular Complications, % 7.0 7.5 NS

Fluorescent time (min) 26.1±11.0 22.9±11.10.02

Operation time (min) 29.7±18.3 29.5±18.2NS

(n=165) ((n=164)n=164)

Procedural Results (1)

Procedural Results (2)Protection Unprotected p

value

After stentingSlow flow 7 (4.1%) 15 (8.8%) 0.07

No flow 1 (0.6%) 3 (1.7%) NS

Distal embolization 4 (2.3%) 10 (5.9%) NS

Post PCISlow flow 7 (4.1%) 13 (7.8%) 0.15

No flow 2 (1.2%) 6 (3.6%) 0.15

Slow flow or No flow 9 (5.3%) 19 (11.4%) 0.05

Distal embolization 4 (2.3%) 7 (4.1%) 0.35

Total incidence 13 (7.6%) 26 (15.5%) 0.027

(n=165) ((n=164) n=164)

GuardWireTM crossed the lesion, % 97Without any procedure, % 41With buddy wire, % 53After balloon dilatation, % 4

Unsuccessful for crossing the lesion, % 1.2Not performed distal protection, % 0.6

Distal embolization after GuardWireTM insertion, % 1.2

n=173

Device Performance Results

Protection Unprotected p Value

In-hospital MACEDeath 5 (3%) 7 (4.0%) NSre-MI 0 1 (0.6%) NSTLR/TVR 0 1 (0.6%) NS

6 month MACE (n=160) (n=152)Death 6 (3.8%) 4 (2.6%) NSre-MI 0 0 NSTLR/TVR 17 (10.6%) 15 (9.9%) NS

((n=173)n=173) ((n=168)n=168)

Clinical Outcomes

Peak CK / CK-MB

29382640

0

500

1000

1500

2000

2500

3000

3500

Protected Unprotected

228 222

0

50

100

150

200

250

300

Protected Unprotected

CKCK CK-MB

n=95 n=85n=95 n=85 n=102 n=97n=102 n=97

IU/ lIU/ l IU/ lIU/ l

11.213

4.6

8.75

6.77.5

0

24

68

1012

14

6hr 18hr 48hr

ProtectedUnprotected

Troponin-Tp=NSp=NS

n=47 n=36n=47 n=36 n=47 n=35n=47 n=35 n=38 n=34n=38 n=34

ng/ml

ST Resolution (90min)

37.534

28.534.3 33.6 32.1

0

10

20

30

40

50

Complete Partial None

ProtectedUnprotectedp=NS%

n=36 n=67n=36 n=67 n=42 n=52n=42 n=52 n=37 n=49n=37 n=49

ST Resolution (180min)

44.9

30.125

42.3

32.525.2

0

10

20

30

40

50

Complete Partial None

ProtectedUnprotectedp=NSp=NS%

n=41 n=71n=41 n=71 n=35 n=44n=35 n=44 n=29 n=35n=29 n=35

LVEF

5455.3

57.1

53.8

55.4

57.1

50

55

60

Post PCI 1M 6M

ProtectedUnprotected

p=NSp=NS

%

p=NS

n=144 n=141n=144 n=141 n=133 n=123n=133 n=123 n=108 n=117n=108 n=117

Angiographic Results

5

77

00 3.5

1720

78

0102030405060708090

100

Protected Unprotected

TIMI 0 TIMI 1 TIMI 2 TIMI 3

% Post-procedural TIMI flowp=0.73

Angiographic Results

2.1

88.8

2.13 05.18.2

90.7

0102030405060708090

100

Protected Unprotected

TIMI 0 TIMI 1 TIMI 2 TIMI 3

%TIMI flow at 6 month

p=0.41

Corrected TIMI Frame Count

24.529 27.3

24.327.8

24.2

0

5

10

15

20

25

30

35

40

Post PCI 1M 6M

Protected Unprotected

p=NSp=NS%%

p=NSp=NS

n=148 n=157n=148 n=157 n=123 n=125n=123 n=125 n=114 n=112n=114 n=112

p=NSp=NS

Post-procedural Blush Score

22.8

26.9 47.9

57

25.2

20.3

0% 20% 40% 60% 80% 100%

Protected

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.26

n=158

n=167

Blush Score at 30-day

9.6

13.4 43.7

60

42.9

30.4

0% 20% 40% 60% 80% 100%

Protected

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.035

n=125

n=126

Blush Score at 6 month

10.6

12.2 44.7

46.9

43.1

42.5

0% 20% 40% 60% 80% 100%

Protected

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.91

n=113

n=114

Post-procedural Blush Score

20.8

23.8 54.3 21.9

27 47.9

62.3

25.2

17

0% 20% 40% 60% 80% 100%

Protected

Aspiration w/oprotection

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.46

n=105

n=53

n=167

Blush Score at 30-days

13.3

7.5 58.8 33.8

13.5 43.7

62.2

42.9

24.4

0% 20% 40% 60% 80% 100%

Protected

Aspiration w/oprotection

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.08

n=80

n=45

n=126

Blush Score at 6 months

11.9

9.9 46.5 43.7

12.3 44.7

47.6

43

40.5

0% 20% 40% 60% 80% 100%

Protected

Aspiration w/oprotection

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.99

n=71

n=42

n=114

Post-procedural Blush Score Proximal RCA

32.4

42.9 38.1

62.2

19.1

5.4

0% 20% 40% 60% 80% 100%

Protected

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.06

n=37

n=42

Blush Score at 30-dayProximal RCA

16.7

14.3 50

73.3

35.7

10

0% 20% 40% 60% 80% 100%

Protected

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.06n=30

n=28

Blush Score at 6 monthProximal RCA

12

7.4 63

48

29.6

40

0% 20% 40% 60% 80% 100%

Protected

Unprotected

Blush 0&1 Blush 2 Blush 3

p=0.55n=25

n=27

Protected Unprotected p(N=173) (N=168) value

Post Ref. Vessel Diam. (mm) 3.07±0.62 3.02±0.54 0.39Diameter stenosis , %

pre (n= 172, 165) 88±19 89 ±17 0.50post (n= 173, 168) 19.3 ±11.7 20.2 ±13.1 0.511Mo (n= 144, 136) 18.0 ±14.2 18.8 ±13.8 0.646Mo (n= 122, 122) 36.3 ±22.3 36.2 ±22.2 0.98

MLD, mmpre 0.32 ±0.49 0.27±0.42 0.30post 2.48 ±0.59 2.40 ±0.53 0.221Mo 2.59 ±0.66 2.47 ±0.60 0.106Mo 1.79±0.76 1.72 ±0.70 0.44

Binary restenosis, % 21.3 23.8 0.65

Angiographic ResultsQCA at 6 month

Trial Total Enroll 341 cases

Sub-Analysis Data Flow

CFR: 50 casesUnroteted:25 casesProtected: 25 cases

Pzf: 35 casesUnroteted:16 casesProtected: 19 cases

Eligible Flow Wire analysis50 cases

-0.000 50.000 100.00 150.00mmHg

BP2

APV 21 cm/sADPV 27 cm/sASPV 12 cm/sDVSR 2.2ESRF (-) CFR 1.6

Pzf=48mmHg

Zero-flow pressure

CoronaryPressure(mmHg)

Coronaryflow

(cm/sec)Pzf

Correlation of Pzf and EF (All)

UnprotectedProtected

20.0 30.0 40.0 50.0 60.0 70.0Pzf

30.0

40.0

50.0

60.0

70.0

80.0LV

EFy= -0.36x + 72.99r = 0.09p = 0.098

%

mm Hg

Correlation of Pzf and EF (LAD)

UnprotectedProtected

40.0 50.0 60.0 70.0Pzf

30.0

40.0

50.0

60.0

70.0

80.0L

VE

Fr = -1.06x + 110.81r = 0.49p = 0.01

%

mm Hg

Conclusions (1)There was no detrimental effect in patients with AMI regarding the usage of the PercuSurge™ distal protection system.

The frequency of in-hospital and 6-month MACE was similar among the protected and control groups.

The incidence of slow flow, no reflow, and distal embolism was lower in the group treated with distal protection than that of unprotected group.

Conclusions (2)A higher incidence of Blush 3 post procedure and at 30days has been observed in the group treated with PercuSurgeTM, especially in the cases with proximal RCA lesions.

These findings may indicate that distal protection is beneficial in terms of prevention of severe flow disturbance and microvascularmyocardial perfusion.

However, further study is necessary to prove the clinical impact of the distal protection therapy on the AMI patients.