Disclosure statement of financial interest

Academic Medical Center Amsterdam

Interventional CardiologyJACC Intv. 2009 Oct; 2 (10): 934-JACC Intv. 2009 Oct; 2 (10): 934-4343

Within the past 12 months, our institution has had a financial interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

Grant/Research Support:

Unrestricted educational grant St. Jude Medical

Disclosure statement of financial interest



Randomized Comparison of Primary PCI Randomized Comparison of Primary PCI with Combined Proximal Embolic Protection with Combined Proximal Embolic Protection and Thrombus Aspiration versus Primary and Thrombus Aspiration versus Primary PCI Alone in STEMIPCI Alone in STEMI

The PREPARE TrialThe PREPARE TrialPRPRoximal oximal EEmbolic mbolic PProtection in rotection in AAcute MI and cute MI and RResolution of ST-esolution of ST-EElevationlevation

Joost D.E. HaeckJoost D.E. Haeck

Karel T. Koch, Luc Bilodeau*, Jan G.P. Tijssen, René J. van der Schaaf, José P.S. Karel T. Koch, Luc Bilodeau*, Jan G.P. Tijssen, René J. van der Schaaf, José P.S. Henriques, Wim. J. Rohling, Allard van der Wal, Jan Baan Jr., Marije M. Vis, Jan J. Henriques, Wim. J. Rohling, Allard van der Wal, Jan Baan Jr., Marije M. Vis, Jan J. Piek, Mitchell W. KrucoffPiek, Mitchell W. Krucoff††, Robbert J. de Winter., Robbert J. de Winter.

Academic Medical Center - University of Amsterdam, The NetherlandsAcademic Medical Center - University of Amsterdam, The Netherlands

*Montréal Heart Institute, QC, *Montréal Heart Institute, QC, CanadaCanada††Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USADuke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA



Inadequate myocardial reperfusion relates to prognosis, Inadequate myocardial reperfusion relates to prognosis, even in the presence of adequate epicardial flow.even in the presence of adequate epicardial flow.

Embolization of atherothrombotic material plays a crucial Embolization of atherothrombotic material plays a crucial role in microvascular obstruction and impaired role in microvascular obstruction and impaired myocardial perfusion.myocardial perfusion.

The ProxisThe Proxis™™ device is a combined system of device is a combined system of proximal proximal embolic protection embolic protection andand thrombus aspiration thrombus aspiration. The device . The device has been shown feasible and safe in primary PCIhas been shown feasible and safe in primary PCI**..

The The PREPAREPREPARE Trial was designed to evaluate primary PCI Trial was designed to evaluate primary PCI with the Proxis system compared to primary PCI alone.with the Proxis system compared to primary PCI alone.

*Koch KT et al. Rev Cardiovasc Med. 2007;8(3): 160-6*Koch KT et al. Rev Cardiovasc Med. 2007;8(3): 160-6

BackgroundBackground



Proxis embolic protection systemProxis embolic protection system

Full length flexible catheterFull length flexible catheter6F and 7F GC compatible6F and 7F GC compatible

Sealing balloon at the tipSealing balloon at the tip

COCO22 based inflation device based inflation device

Deployed proximal to target Deployed proximal to target lesion before crossinglesion before crossing

Inflation of balloon suspends Inflation of balloon suspends antegrade flow during lesion antegrade flow during lesion interventionintervention

Stagnated blood and emboli, Stagnated blood and emboli, liberated during intervention liberated during intervention are retrieved by gentle are retrieved by gentle aspirationaspiration ProxisProxis™™ embolic protection system (St. Jude Medical, St. Paul, MN, USA) embolic protection system (St. Jude Medical, St. Paul, MN, USA)



• PRPRoximal oximal EEmbolic mbolic PProtection in rotection in AAcute MI and cute MI and RResolution of ST-esolution of ST-EElevationlevation

• Investigator-initiated randomized trialInvestigator-initiated randomized trial

• Comparison of primary PCI with Proxis system Comparison of primary PCI with Proxis system versus primary PCI aloneversus primary PCI alone

• Open trial with blinded evaluation of end pointsOpen trial with blinded evaluation of end points

• Participation of 2 centersParticipation of 2 centers

• 140 patients in each study arm140 patients in each study arm

PREPARE TrialPREPARE Trial



Inclusion criteriaInclusion criteria

• Consecutive STEMI patients Consecutive STEMI patients ≤ 6 h≤ 6 h

• ST-segment elevation ST-segment elevation ≥ 2 mm in ≥ 2 leads≥ 2 mm in ≥ 2 leads

• TIMI flow grade 0 to 1 at first angiogramTIMI flow grade 0 to 1 at first angiogram

• Coronary anatomy suitable for ProxisCoronary anatomy suitable for Proxis

• ECG suitable for ST-segment resolution ECG suitable for ST-segment resolution

evaluationevaluation

Exclusion criteriaExclusion criteria

• Recurrence of MI in same areaRecurrence of MI in same area

• Prior CABG or lyticsPrior CABG or lytics

Patient selectionPatient selection



UFH 70 U/kgUFH 70 U/kgASA 300 mgASA 300 mgClopidogrel 600 mgClopidogrel 600 mg

Continuous Continuous ST HolterST Holter

Coronary angiogramCoronary angiogram

STEMI ≤ 6 hSTEMI ≤ 6 h

Primary PCIPrimary PCIalonealone

Clinical follow up at 30 daysClinical follow up at 30 days

Primary PCIPrimary PCIwith Proxiswith Proxis

PREPARE TrialPREPARE Trial

Study flow chartStudy flow chart

RR24 h24 h



Primary end pointPrimary end point • ST-segment elevation resolution (STR) over time*ST-segment elevation resolution (STR) over time*

Secondary end pointsSecondary end points• ST-segment curve areaST-segment curve area

• TIMI graded flow TIMI graded flow

• Myocardial blush gradeMyocardial blush grade

• Angiographic signs of distal embolizationAngiographic signs of distal embolization

• Composite of death, MI, TVR, and stroke at 30 daysComposite of death, MI, TVR, and stroke at 30 days

End pointsEnd points

*Duke Clinical Research Institute Core Lab*Duke Clinical Research Institute Core Lab



Patient characteristicsPatient characteristics

AgeAge 62 ± 1162 ± 11 59 ± 1159 ± 11

MaleMale 80% 80% 80%80%

Family history CADFamily history CAD 35%35% 38%38%

HypercholesterolemiaHypercholesterolemia 21%21% 13%13%

Current smokingCurrent smoking 50% 50% 65%65%

HypertensionHypertension 31%31% 23%23%

DiabetesDiabetes 12%12% 6%6%

Previous MIPrevious MI 6%6% 9%9%

Multivessel diseaseMultivessel disease 33%33% 31%31%

Symptoms to balloon (min) Symptoms to balloon (min) 170 170 153 153

ProxisProxisn = 141n = 141

ControlControln = 143n = 143

**

**

*p*p≤≤0.030.03





Infarct related arteryInfarct related artery

RCARCA 61%61% 60%60%

LADLAD 29%29% 29%29%

LCxLCx 10%10% 11%11%

Pre-PCI TIMI graded flowPre-PCI TIMI graded flow

00 90%90% 89%89%

11 9%9% 8%8%

22 1% 1% 4% 4%

Lesion characteristicsLesion characteristics





Procedural characteristicsProcedural characteristics

*P<0.05; IQR interquartile range*P<0.05; IQR interquartile range

Procedural successProcedural success 100%100% 99%99%

Proxis placedProxis placed 94%94% ──

Predilatation and stentingPredilatation and stenting 87%87% 76%76%

Direct stenting Direct stenting 11% 11% 19%19%

Balloon angioplastyBalloon angioplasty 3% 3% 6% 6%

GP IIb/IIIa receptor antagonistsGP IIb/IIIa receptor antagonists 43% 43% 35%35%

Additional thrombus aspirationAdditional thrombus aspiration 6% 6% 6%6%

Pathology confirmed thrombusPathology confirmed thrombus 75% 75% ─ ─

Puncture to balloon (min)Puncture to balloon (min)

MedianMedian 17 17 14*14*

IQRIQR 13-23 13-23 10-1810-18

**





ImmediateImmediate 66%66% (85/129)(85/129) 50%50% (67/135)(67/135) 0.0090.009

30 min30 min 74%74% (96/130)(96/130) 64%64% (87/135)(87/135) 0.110.11

60 min60 min 80%80% (101/126)(101/126) 72%72% (93/129)(93/129) 0.140.14

90 min90 min 81%81% (100/124)(100/124) 74%74% (97/131)(97/131) 0.230.23

120 min120 min 78%78% (98/126)(98/126) 76%76% (100/131)(100/131) 0.880.88

Complete (Complete (≥≥70%) STR 70%) STR

(Fisher’s Exact Test)(Fisher’s Exact Test)



P-valueP-value



Complete STR over timeComplete STR over time

Last Last contrastcontrast

4040

5050

6060

7070

8080

9090

3030 6060 9090 120120

Time after last contrast, minTime after last contrast, min

Pa

tie

nts

wit

h c

om

ple

te S

TR

, %

Pa

tie

nts

wit

h c

om

ple

te S

TR

, %

P=0.009P=0.009

ControlControl

ProxisProxis



ST- resolution %ST- resolution %

ImmediateImmediate 73 ± 2773 ± 27 63 ± 3263 ± 32 0.0090.009

30 min30 min 78 ± 2178 ± 21 74 ± 2474 ± 24 0.180.18

60 min60 min 82 ± 2082 ± 20 78 ± 2178 ± 21 0.270.27

90 min90 min 82 ± 1982 ± 19 80 ± 2180 ± 21 0.170.17

120 min120 min 82 ± 19 82 ± 19 81 ± 20 81 ± 20 0.48 0.48

ST- curve areaST- curve area**** (µV/min)(µV/min)

MedianMedian 51925192 6250 6250 0.0370.037

IQRIQR (3793-7626)(3793-7626) (4221-9186) (4221-9186)

Continuous ST-recovery parametersContinuous ST-recovery parametersP-valueP-value**ProxisProxis

n = 141n = 141ControlControl

n = 143n = 143

Mean (SD); Mean (SD); **T-TestT-Test * * **Area under ST-deviation versus time trend curve is from last contrast to 3 hours after procedure Area under ST-deviation versus time trend curve is from last contrast to 3 hours after procedure



Procedural parametersProcedural parametersProxisProxisn = 141n = 141


*Cochran-Armitage Test*Cochran-Armitage Test††Fisher’s Exact TestFisher’s Exact Test

‡‡Mann Whitney U TestMann Whitney U Test

Post-PCI TIMI graded flowPost-PCI TIMI graded flow33 93%93% 87%87%

22 7%7% 11%11% 0.060.06**

0-10-1 0%0% 2%2%

Myocardial blush gradeMyocardial blush grade 33 81%81% 83%83%

22 16%16% 11%11% 0.930.93**

0-10-1 4%4% 6%6%

Distal embolization Distal embolization (yes/no)(yes/no) 10%10% 14%14% 0.360.36††

Infarct size by peak CK-MB Infarct size by peak CK-MB ((μμg/L)g/L)

MedianMedian 204204 246246 0.220.22‡‡

IQRIQR 136-378136-378 154-413154-413

P-valueP-value††



Debris confirmed by pathologyDebris confirmed by pathology 75%75% (84/112)(84/112)

Before stentingBefore stenting 87%87% (73/84)(73/84)

Both before and after stentingBoth before and after stenting 35%35% (29/84)(29/84)

Only after stentingOnly after stenting 13%13% (11/84)(11/84)

Only thrombusOnly thrombus 50%50% (42/84)(42/84)

Thrombus and plaque-componentsThrombus and plaque-components 49%49% (41/84)(41/84)

Only plaque-componentsOnly plaque-components 1%1% (1/84)(1/84)

Pathology resultsPathology resultsProxisProxisn = 112n = 112



DeathDeath 22 22

MIMI 22 33

TVRTVR 33 66

StrokeStroke 00 11

MACCEMACCE** 66 (4%)(4%) 1010 (7%)(7%)

no complications at Proxis landing zoneno complications at Proxis landing zone

Clinical events at 30 daysClinical events at 30 daysProxisProxisn = 141n = 141


For descriptive purposes only; no statistical comparisons doneFor descriptive purposes only; no statistical comparisons done*ARC MACCE definition Circ. 2007; 115: 2344–2351*ARC MACCE definition Circ. 2007; 115: 2344–2351



All patientsAll patients 66%66% (85/129)(85/129) 50%50% (67/135)(67/135) 0.0090.009

Infarct-related arteryInfarct-related arteryAnteriorAnterior 42%42% (16/38)(16/38) 18%18% (7/40)(7/40) 0.030.03Non-anteriorNon-anterior 76%76% (69/91)(69/91) 63%63% (60/95)(60/95) 0.080.08

Baseline thrombusBaseline thrombusYesYes 65%65% (64/98)(64/98) 50%50% (46/92)(46/92) 0.040.04NoNo 68%68% (21/31)(21/31) 49%49% (21/43)(21/43) 0.150.15

Symptom onset to balloonSymptom onset to balloon< 3 hours< 3 hours 68%68% (47/69)(47/69) 49%49% (43/87)(43/87) 0.020.02≥ ≥ 3 hours3 hours 63%63% (38/60)(38/60) 50%50% (24/48)(24/48) 0.180.18

GP IIb/IIIa antagonistsGP IIb/IIIa antagonistsYesYes 56%56% (29/52)(29/52) 28%28% (13/46)(13/46) 0.0080.008No No 72%72% (56/77)(56/77) 61%61% (54/89)(54/89) 0.140.14

P-valueP-valueProxisProxisn = 129n = 129


(Fisher’s Exact Test)(Fisher’s Exact Test)

Subgroup analysis complete STR at last contrast



The Proxis system is The Proxis system is feasiblefeasible and and safesafe in the setting of STEMI, in the setting of STEMI,

and effectively retrieves embolic debris in most patients.and effectively retrieves embolic debris in most patients.

Complete STR wasComplete STR was faster faster andand more frequent more frequent inin Proxis Proxis treated treated

patientspatients, with, with reduction of ECG injury current over time, reduction of ECG injury current over time,

compared to control patients.compared to control patients.

The results of the PREPARE trial suggest that primary PCI with The results of the PREPARE trial suggest that primary PCI with

combined proximal embolic protection and aspiration leads tocombined proximal embolic protection and aspiration leads to

better immediate microvascular flowbetter immediate microvascular flow in STEMI patients. in STEMI patients.

In conclusionIn conclusion



PREPARE TrialPREPARE TrialPRPRoximal oximal EEmbolic mbolic PProtection in rotection in AAcute MI and cute MI and RResolution of ST-esolution of ST-EElevationlevation

Thank you for your attentionThank you for your attention

[email protected]@amc.uva.nl

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Disclosure statement of financial interest