1. MACE Trial Rationale, Study Design, and Current Status
David J. Cohen, MD, MSc
Director of Cardiovascular Research Saint-Luke’s Mid America Heart Institute
Missouri Endowed Professor of Medicine
University of Missouri-Kansas City School of Medicine
DJC-CRT 2015

2. Disclosures Grant Support/Drugs Grant Support/Devices
Daiichi-Sankyo - Eli Lilly
Astra-Zeneca - Merck
Grant Support/Devices
Edwards Lifesciences - Abbott Vascular
Medtronic - Boston Scientific
CSI, Inc. - Covidien
Consulting/Advisory Boards
Medtronic - Astra-Zeneca
Eli Lilly
DJC: 2/15

3. Challenges in Treating Calcified Coronary Lesions
Prone to dissection with POBA and other standard PTCA techniques
Inability to dilate
Incomplete stent expansion increased stent thrombosis and restenosis
Inhibition of drug delivery/absorption

4. Impact of Severe Calcification on DES Outcomes
Cardialysis Study
Pooled data from 7 DES trials (6296 pts)
Presence of severe coronary calcification determined by angiographic core lab
Severe calcification present in 20% of pts associated with worse outcomes across full spectrum of endpoints
P<0.01 for all comparisons
Bourantas C, et al. EuroPCR 2014

5. Rationale for the MACE Study
Previously, no device was specifically FDA approved for treatment of coronary calcification
Recently, the Diamondback 360 catheter was approved for the indication of “facilitating stent delivery in patients with CAD… due to severely calcified coronary lesions”
Nonetheless, there remain numerous gaps in knowledge about the treatment of CAD in this challenging patient population

6. MACE Study
Multicenter Prospective Study to Evaluate Outcomes of Moderate to Severely Calcified Coronary Lesions

7. MACE Study: Organization
Study Sponsor: Cardiovascular Systems, Inc.
Principal Investigator Samin K. Sharma, MD Mount Sinai Medical Center, New York
Angiographic Core Laboratory Jeffrey J. Popma, MD Beth Israel Deaconess Medical Center, Boston
Economic Core Laboratory Saint Luke’s Mid America Heart Institute, Kansas City MO

8. MACE Study: Objectives
To determine the impact of both moderate and severe coronary calcification on the outcomes of PCI using contemporary devices and pharmacotherapy
To evaluate the impact of coronary calcification on the short- and long-term costs of PCI
To serve as a virtual “control group” to better understand the benefits of orbital atherectomy in patients with severe coronary calcification

9. MACE Study: Design
Enroll up to 500 subjects
2002 subjects with:
Moderate calcification
1001 subjects with:
None/mild calcification
Severe calcification
All patients biomarker negative at entry ensures accurate assessment of periprocedural MI
Real-world design Treatment using any FDA approved device(s) per operator discretion
3 year follow-up for all patients for both clinical and economic outcomes

10. Assessment of Calcification
 Ca++ Severity
Angiographic Appearance*
IVUS/OCT
None/Mild
Absence of readily apparent radiopacities at the site of stenosis
≤ 180° of calcium at one (1) cross section
Moderate
Presence of radiopacities only during cardiac cycle before contrast injection
181° to 269° of calcium at 1 cross section
Severe
Presence of radiopacities noted without cardiac motion
Involves both sides of the arterial wall in at least one location
Total length of calcium at least 15mm and extend partially into the target lesion, or
≥ 270° of calcium at 1 cross section.
* Assessed by core laboratory

11. Study Endpoints Primary Endpoint
30-day MACE: composite of cardiac death, MI (CKMB >3x ULN), or TVR
Secondary Endpoints
MACE at 1 year
TLR
Procedural and device success
Cardiovascular Related Costs: In-hospital (billing data), 1-year, 3-years

12. Study Update (as of 1/19/15) 34 activated sites 293 subjects enrolled
First 50 Patients
34 activated sites
293 subjects enrolled
Calcification
None/Mild 93 pts
Moderate 100 pts
Severe 98 pts
Characteristic
Mean Value
Male
64%
Age (yrs)
67 yrs
Diabetes
40%
Prior CABG 6%
Target Vessel
LAD/LM
LCx/Ramus
32%
RCA
28%

13. Summary (1)
MACE is the first study that will prospectively assess short and long-term PCI outcomes according to the extent of coronary calcification as assessed by a centralized core laboratory
Patients from MACE will also serve as a “virtual control group” for the ORBIT II trial in order to better understand the benefits of orbital atherectomy in contemporary practice for patients undergoing PCI for treatment of calcified coronary lesions

14. Summary (2)
Detailed health economic data will be collected to better understand the cost-effectiveness of alternative strategies for managing calcified coronary lesions
Preliminary results for 30 day outcomes are expected in late 2015