1. ISAR-LEFT MAIN 2 Randomized Trial Zotarolimus- vs
ISAR-LEFT MAIN 2 Randomized Trial Zotarolimus- vs. Everolimus-Eluting Stents for Treatment of Unprotected Left Main Coronary Artery Lesions
Julinda Mehilli, MD
Klinikum der Universitaet Munich
Deutsches Herzzentrum Munich
Germany

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Lecture fees
Abbott Vascular
Daichii Sankyo/Lilly
The Medicines
Terumo

3. PCI vs. CABG Surgery for uLMCA
Meta-analysis of Randomized Controlled Studies
Similar Risk of Death or Myocardial Infarction
Higher Risk of Revascularization
Capodanno et al., J Am Coll Cardiol 2011

4. First Generation DES for uLMCA Similar Clinical & Angiographic Performance
ISAR-LEFT MAIN
Mehilli et al., J Am Coll Cardiol 2009

5. Second Generation DES for uLMCA Improved Clinical Performance
PRECOMBAT 2 trial
Ischemia-driven TVR
MACE
Kim YH et al., J Am Coll Cardiol, Interv 2012

6. Second Generation DES for All-Comers
Resolute All Comers trial
Serruys et al., New Engl J Med 2010 5

7. ISAR-LEFT MAIN 2 DESIGN: Randomized, multi-center trial OBJECTIVE:
To evaluate the relative performance of two 2nd generations DES – zotarolimus- and everolimus-eluting stents – in patients with uLMCA lesions
STEERING COMMITTEE
Adnan Kastrati, MD (Chair)
Julinda Mehilli, MD (principal investigator)
Josef Dirschinger, MD
PARTICIPATING CENTERS
Deutsches Herzzentrum & Klinikum rechts der Isar, Munich, Germany
PI: J. Mehilli & K-L Laugwitz
Bad Segeberger Kliniken, Bad Segeberg, Germany
PI: G Richart
Department of Cardiology, University of Ferrara, Italy
PI: M Valgimigli 6

8. Inclusion Criteria
Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥50 % stenosis located in unprotected LMCA who are unable to undergo CABG because of cardiac surgeons’ refusal (poor surgical candidates) or their own unwillingness

9. Exclusion Criteria Age < 18 years Cardiogenic shock
ST-Elevation Acute Myocardial Infarction
In-stent Restenosis
Prior coronary artery bypass surgery
Malignancies with life expectancy <1 year
Planned staged PCI within 30 days from index PCI
Planned elective surgical procedure necessitating interruption of clopidogrel during the first six months after PCI
Pregnancy

10. Primary Endpoint
Incidence of major adverse cardiac events defined as the composite of
death
myocardial infarction
target lesion revascularization
at 1-year follow-up

11. Secondary Endpoints
left main area analysis
Angiographic restenosis at 8-month FU angiogram, defined as diameter stenosis ≥50% measured by QCA in the area from left main ostium to 5-mm proximal segments of LAD, LCx as well as of R. intermedius if the latter has a reference diameter >2 mm
ARC-defined stent thrombosis
at 1-year follow-up

12. Sample Size Calculation
Hypothesis:
Endeavor Resolute stent is not inferior to Xience stent in terms of major adverse cardiac events
Assumptions:
Incidence of MACE 25% in both stent groups
Margin of non-inferiority 9%
Power of 80%
-level of 0.05
Rate of lost to follow-up 5%
Planed number of patients for each group: 300

13. ISAR-LEFT MAIN 2 Trial 650 patients with uLMCA lesions
pre-treated with 600 mg clopidogrel
Zotarolimus-eluting stent
(Endeavor Resolute)
N= 324
Everolimus-eluting stent
(Xience)
N= 326
Angiographic follow-up at 8 months in 73% (N=237)
Angiographic follow-up at 8 months in 69% (N=226)
Clinical follow-up at 12 months in 100% (N=324)
Clinical follow-up at 12 months in 100% (N=326)

14. Baseline Characteristics
Resolute
n=324
Xience
n=326
Age, years
69.4±10.4
70.2±9.4
Women, % 27 23
Art. hypertension, % 68 70
Diabetes, % 28 29
Current smoker, % 15 13
Hypercholesterolemia, % 69 76

15. Baseline Characteristics
Resolute
n=324
Xience
n=326
Acute Coronary Syndrome, % 38 33
History of MI, % 32 29
Prior PCI, % 52 54
Creatinine serum level, mg/dl
1.09±0.71
1.09±0.70
Parsonnet Score
13.3±10.3
13.7±11.0
EuroSCORE
5.1±3.7
5.0±3.7
Malignancies, % 22 24

16. Angiographic Characteristics
Resolute
n=324
Xience
n=326
LV ejection fraction, %
52.1±11.9
53.8±11.4
Coronary artery dominance
right
left
balanced 84 10 6 9 7
RCA ≥50% stenosis, % 69 74
Dominant RCA occlusion, % 11
R. intermedius >2.0 mm, % 16

17. Left Main Area Lesion Location%
Distal
Midshaft
Ostium
Resolute
n=324
Xience
n=326

18. Stenting Technique % Single stenting Culotte stenting T-stenting
Crush stenting
Resolute
n=324
Xience
n=326

19. Incidence of Stent Thrombosis - secondary endpoint -%
Probable stent thrombosis
Definite stent thrombosis
Resolute
n=324
Xience
n=326

20. Major Adverse Cardiac Events - primary endpoint -
100
RR 1.26 (95% CI )
P= .25 80 60
Resolute
Cumulative incidence, %
Xience 40
17.5% 20
14.3% 1 2 3 4 5 6 7 8 9 10 11 12
Months after randomization

21. Death or Myocardial Infarction
100
RR 1.28 (95% CI )
P= .42 80 60
Resolute
Cumulative incidence, %
Xience 40 20
7.5%
5.9% 1 2 3 4 5 6 7 8 9 10 11 12
Months after randomization

22. Death or Myocardial Infarction or Stroke
100
RR 1.26 (95% CI )
P= .43 80 60
Resolute
Cumulative incidence, %
Xience 40 20
8.1%
6.5% 1 2 3 4 5 6 7 8 9 10 11 12
Months after randomization

23. Cumulative incidence, %
All-Cause Mortality
100
RR 1.01 (95% CI )
P= .98 80 60
Resolute
Cumulative incidence, %
Xience 40 20
5.6%
5.6% 1 2 3 4 5 6 7 8 9 10 11 12
Months after randomization

24. LMCA Area Restenosis Resolute P=.20 P=.35 Xience %
Angiographic restenosis
Clinical restenosis

25. Target Lesion Revascularization
Resolute
RR 1.26 (95% CI )
P= .35
Xience %
TLR
Repeat PCI
Bypass surgery

26. MACE in Different Subgroups
Resolute
Xience
Relative Risk
(95% CI)
P Value
for Interaction
No. of Events/Total (%)
Diabetes
0.96
Yes
24/92 (26.2)
20/93 (21.9) No
32/232 (14.0)
26/233 (11.3)
Parsonnet score
0.68
>15
28/120 (23.7)
24/115 (21.0)
≤15
28/204 (13.9)
22/211 (10.6)
EuroSCORE
0.52 ≥6
29/140 (20.7)
23/120 (19.5)
<6
27/184 (15.0)
23/206 (11.3)
0.5 1
1.5 2
2.5 3
Resolute better
Xience better

27. Summary
The use of 2nd gen. DES in unprotected LMCA lesions in relatively unselected patients is safe and effective.
Both Endeavor Resolute and Xience stents provide similar clinical and angiographic outcomes at one-year follow-up in this high risk patient population.