Slide 1: The MASTER II Trial: MGuard Embolic Protection Stent vs Standard Stents in AMI
The MASTER II Trial Comparison of the MGuard Embolic Protection Stent with Standard Stents in Acute Myocardial Infarction Gregg W. Stone, MD Columbia University Medical Center NewYork - Presbyterian Hospital Cardiovascular Research Foundation
Slide 2: Background
Background • In the randomized MASTER I trial, among 433 pts with STEMI undergoing primary PCI, treatment with the MGuard stent compared to standard BMS/DES resulted in improved rates of TIMI - 3 flow and ST - segment resolution, a trend toward lower mortality at 30 - days and 1 year, but greater ra
Slide 3: The MGuard and MGuard Prime Embolic Protection Stent (EPS)
The MGuard and MGuard Prime Embolic Protection Stent (EPS) *InspireMD, Tel Aviv, Israel; ** Polyethyleneterephthalate MGuard MGuard Prime Metallic frame 316L stainless steel L605 cobalt chromium Strut width 100 µm 80 µm Crossing profile 1.1 – 1.3 mm 1.0 – 1.2 mm Shaft dimensions 0.65 – 0.86 mm 0.65
Slide 4: The MASTER I Trial
M GUARD for A cute ST E levation R eperfusion The MASTER I Trial STEMI with symptom onset within 12 hours at 433 pts at 50 sites in 9 countries Substudies: Cardiac MRI : 60 pts (30 pts in each arm) at 3 - 5 days Angio FU: 5 0 pts in MGuard arm at 13 months Follow - up: 30 days, 6 months, 1 year Prim
Slide 5: MASTER I Results
MASTER I Results *191 (88%) MGuard, 26 MGuard Prime; **39.8% DES; † <50% final residual stenosis using only the randomized stent; ‡ < 50% final residual stenosis and TIMI - 3 flow MGuard stent (n=217)* Control stent (n=216)** P value Device success † 95.9% 99.1% 0.03 TIMI - 3 flow achieved 91.7% 82.
Slide 6: The MASTER II Trial
M GUARD for A cute ST E levation R eperfusion II The MASTER II Trial STEMI with symptom onset within 12 hours - 1,114 pts at 70 sites in 11 countries - Follow - up: 30 days, 6 months, 1 year, 2 years, 3 years 1 ° efficacy endpoint : ST - segment resolution at 60 - 90 minutes (Sup) 1 ° safety endpoin
Slide 7: Principal Inclusion Criteria
MASTER II Principal Inclusion Criteria • Symptoms consistent with STEMI between 30 mins and 12 hrs of symptom onset • ≥ 2 mm of ST - segment elevation in ≥ 2 contiguous leads • TIMI 2 or 3 flow restored either spontaneously, by aspiration or pre - dilatation • PCI of a single de novo lesion with RVD
Slide 8: Principal Exclusion Criteria
MASTER II Principal E xclusion Criteria • LBBB, paced rhythm, etc. • Prior PCI w/i 30d or planned non - TV PCI w/i 7d or planned TV - PCI w/i 12 months • Cardiogenic shock or CPR • ≥50% left main stenosis present • Infarct lesion ostial or bifurcation with ≥ 2.0 mm sidebranch • T arget vessel or inf
Slide 9: Study Organization
MASTER II Study Organization Principal investigator: Gregg W. Stone Co - principal investigator: Jose PS Henriques Steering committee: Gregg W. Stone , Jose PS Henriques, Eli Bar, Donald Cutlip, Ori Ben - Yehuda Data monitoring: Medpace Medical Device, Minneapolis, MN, USA; MEDPASS , Paris, France a
Slide 10: Enrollment
MASTER II Enrollment 1. Enrollment was voluntarily suspended on April 30 th , 2014 after 310 patients had been randomized at 46 international sites because of a higher than expected rate of stent dislodgement with the MGuard Prime 2. No patient in MASTER II experienced an endpoint event due to a ste
Slide 11: Top Enrolling Sites
MASTER II Top 12 Enrolling Sites 1. Peep Laanmets , North Estonia Regional Hospital, Tallinn, Estonia 22 2. Andreas Baumbach, Bristol Heart Institute, Bristol, UK 21 3 . Marek Kondys , III Oddzial Kardiologii , Dabrowa Gornicza , Poland 20 4. Niels van Royen, VUMC Amsterdam, Amsterdam, Netherlands 1
Slide 12: Baseline Characteristics
MASTER II Baseline Characteristics MGuard Prime (n=155) Control stent (n=155) Age (years) 60 [52, 66] 62 [55, 70] Male 79.4% 73.5% Hypertension 40.6% 49.7% Hyperlipidemia 31.6% 28.4% Diabetes mellitus 13.5% 18.1% Cigarette smoking 52.3% 45.5% Prior MI 7.1% 6.5% Prior PCI 7.1% 5.2% Symptoms to device
Slide 13: Procedural Medications
MASTER II Procedural Medications MGuard Prime (n=155) Control stent (n=155) P value Anticoagulation, peri - procedural – Unfractionated heparin 70.1% 67.8% 0.65 – Glycoprotein IIb/IIIa inhibitor 45.5% 53.3% 0.17 – Bivalirudin 37.0% 31.6% 0.32 Anti - platelet agents, discharge – Aspirin 98.7% 96.7% 0
Slide 14: Procedures
MASTER II Procedures MGuard Prime (n=155) Control stent (n=155) P value Aspiration performed 60.6% 62.6% 0.73 Balloon pre - dilatation performed 49.7% 34.8% 0.008 Direct stenting 13.5% 18.1% 0.28 ≥1 stent implanted 99.4% 99.4% 1.00 ≥2 stents implanted 9.7% 14.2% 0.22 Stent type – MGuard Prime 96.8%
Slide 15: Device Success
MASTER II Device Success Device success: < 50% final residual stenosis using only the randomized stent Lesion success: < 50% final residual stenosis using any percutaneous method Angiographic success: < 50% final residual stenosis and final TIMI 3 flow 92.3 96.7 100 91.4 98.7 98.1 98.1 88.3 80 85 90
Slide 16: Procedural Results
MASTER II Procedural Results MGuard Prime (n=152) Control stent (n=155) P value TIMI flow = 3 91.4% 89.0% 0.46 TIMI flow = 2 7.9% 9.1% 0.71 TIMI flow = 0/1 0.7% 1.9% 0.62 Corrected TIMI frame count 19.5 [14.0, 24.0] 18.0 [14.0, 24.0] 0.47 IPTE* 11.2% 11.6% 0.91 RVD, mm 3.07 [2.77, 3.37] 3.05 [2.72,
Slide 17: Primary Endpoint: Complete ST-segment resolution
MASTER II Primary Endpoint Complete ST - segment resolution MGuard Prime (n=144) Control (n=145) 59.3% 29.7% 11.0% 56.9% 32.6% 10.4% Difference [95%CI] = - 2.4% [ - 14.5,9.7] P=0.68
Slide 18: 30-day Clinical Events
MASTER II 30 - day Clinical Events MGuard Prime (n=155) Control stent (n=155) P value MACE 4 (2.6%) 7 (4.5%) 0.36 – Cardiac mortality 1 (0.6%) 3 (1.9%) 0.62 – Reinfarction 2 (1.3%) 2 (1.3%) 1.00 – TLR, ischemia - driven 4 (2.6%) 4 (2.6%) 1.00 Death, all - cause 1 (0.6%) 3 (1.9%) 0.62 TVR, ischemia -
Slide 19: 30-Day MRI Substudy
MASTER II 3 - 5 Day MRI Substudy MGuard Prime (n=28) Control stent (n=29) P value Total LV myocardial mass, gms 129.5 [107.0, 154.5] 122.0 [112.0, 136.0] 0.57 Infarct mass, grams 31.4 [14.9, 50.5] 35.8 [16.4, 57.1] 0.45 Infarct mass (% total LV mass) 23.6 [14.2, 30.1] 29.3 [14.3, 43.0] 0.16 Total MV
Slide 20: Limitations
MASTER II Limitations • Single - blind • Most control pts received DES → substantial difference between MGuard Prime and control arm in restenosis anticipated → trial terminated • Early termination → underpowered for all endpoints
Slide 21: I + II Pooled Analysis
MASTER I + II Pooled Analysis MASTER I MASTER II Number of patients 433 310 - MRI substudy 59 57 Number of sites 50 46 Control arm: DES 39.8% 80.5% MGuard arm: % Prime 12.0% 100% Prasugrel/ticagrelor at d/c 30.1% 63.7% Bivalirudin 11.8% 34.3% GP IIb/IIIa inhibitor 83.1% 49.3% Symptoms to device, min
Slide 22: I + II Procedural Results
MASTER I + II Procedural Results MGuard (n=372) Control stent (n=371) P value Any device failure 5.6% 1.3% 0.03 Device success 96.2% 98.7% 0.04 Lesion success 100% 98.9% 0.62 Angiographic success 91.6% 84.9% 0.005 TIMI flow = 3 91.6% 85.4% 0.008 TIMI flow = 2 7.0% 10.5% 0.09 TIMI flow = 0/1 1.4% 4.1
Slide 23: I + II Complete ST-segment Resolution
MASTER I + II Complete ST - segment resolution MGuard (n=348) Control (n=351) 50.7% 34.8% 14.5% 57.5% 28.4% 14.1% Difference [95%CI] = 6.8% [ - 0.9,14.4 ] P=0.07
Slide 24: I + II 30-day Clinical Events
MASTER I + II 30 - day Clinical Events MGuard (n=372) Control stent (n=371) P value MACE 8 (2.2%) 12 (3.2%) 0.36 – Cardiac mortality 1 (0.3%) 7 (1.9%) 0.04 – Reinfarction 5 (1.3%) 4 (1.1%) 1.00 – TLR, ischemia - driven 8 (2.2%) 5 (1.3%) 0.40 Death, all - cause 1 (0.3%) 7 (1.9%) 0.04 TVR, ischemia -
Slide 25: I + II 30-day Mortality
MASTER I + II 30 - day Mortality
Slide 26: I + II 30-Day MRI Substudy
MASTER I + II 3 - 5 Day MRI Substudy MGuard (n=58) Control stent (n=58) P value Total LV myocardial mass, gms 135.5 [112.0, 158.0] 130.0 [117.0, 156.0] 0.57 Infarct mass, grams 21.9 [12.5, 40.0] 29.0 [16.0, 48.7] 0.22 Infarct mass (% total LV mass) 20.5 [8.9, 28.1] 21.5 [12.0, 30.1] 0.26 Total MVO,
Slide 27: Conclusions
MASTER II Conclusions • The MASTER II trial was terminated prematurely due to the control arm shift in physician preference from BMS to DES, accelerating the plans to create a drug - eluting MGuard • The significant differences in complete ST - segment resolution and TIMI - 3 flow present in MASTER
Slide 28: MASTER I and MASTER II Conclusions
MASTER I and MASTER II Conclusions • The pooled data from 743 randomized pts in the MASTER I and MASTER II trials suggest that compared to control stents, the MGuard may be associated with improved reperfusion success and reduced 30 - day mortality • An adequately powered randomized trial is warrant