1. ISAR-LEFT MAIN: A Randomized Clinical Trial on Drug-Eluting Stents for Unprotected Left Main Lesions
J. Mehilli, MD Deutsches Herzzentrum Technische Universität Munich Germany

2. Sponsor Investigator initiated trial
with financial supported in part by
Deutsches Herzzentrum Munich and in part by
unrestricted grant from Cordis, J&J

3. Background
Recent evidence has shown that DES are at least as safe but much more effective in reducing the need for reintervention as BMS in different patient and lesion subsets.
Currently available DES might not necessarily be associated with equal performance. Potential differences in safety and efficacy between DES may be important when treating uLMCA lesions.
Despite the multitude of comparative DES studies for a variety of lesion characteristics no similar studies have been performed for patients with uLMCA disease.

4. Objective of ISAR-LEFT MAIN
…to assess the relative efficacy of the paclitaxel-eluting stent (Taxus) and sirolimus-eluting stent (Cypher) in patients with unprotected LMCA lesions.

5. Inclusion Criteria
Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥50 % stenosis located in unprotected LM lesions
Informed, written consent

6. Exclusion Criteria Age < 18 years Cardiogenic shock
ST-elevation acute myocardial infarction
In-stent restenosis
Prior coronary artery bypass surgery
Left main size >4.5 mm by visual estimation
Malignancies with life expectancy <1 year
Planned staged PCI within 30 days from index PCI
Planned elective surgical procedure necessitating discontinuation of clopidogrel during the first 6 months
Pregnancy

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

8. Secondary End Point
left main area analysis
Angiographic restenosis at 6-9-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

9. Sample size calculation
Hypothesis:
Taxus is not inferior to Cypher in terms of major adverse cardiac events
Assumptions:
Incidence of MACE 20% in the Cypher group
Margin of non-inferiority 8%
Power of 80%
-level of 0.05
Needed number of patients for each group: 302

10. ISAR-LEFT MAIN 607 patients with unprotected left main lesions
Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for Unprotected Coronary Left Main Lesions
607 patients with unprotected left main lesions
Clopidogrel 600 mg at least 2h before procedure
Aspirin 500mg i.v.
Paclitaxel-eluting stent
(Taxus)
n=302
Sirolimus-eluting stent
(Cypher)
n=305
Clopidogrel 2x75 mg/day until discharge 75 mg indefinitely
Aspirin 200 mg/day

11. Follow-Up Protocol 30 d 6-9 mo. 12 mo. 600 mg Clopidogrel PCI
ASS 500 mg + heparin with/out GPI (10%) or bivalirudin (15%)
30 d
6-9 mo.
12 mo.
serial CK
+ CKMB
measurements
clinical follow-up
(100%)
repeat angiography
(87%)
clinical follow-up
(100%)

12. Baseline clinical characteristics
Taxus
n=302
Cypher
n=305
Age, years
68.8±10.3
69.3±9.3
Women, % 25 20
Art. hypertension, % 70 69
Diabetes, % 30 28
Current smoker, % 10
Hypercholesterolemia, % 78 75

13. Baseline clinical characteristics (con’t)
Taxus
n=302
Cypher
n=305
Acute coronary syndrome, % 44 40
History of MI, % 25 28
Prior PCI, % 46 50
Parsonnet score
12.8±9.8
12.0±9.1
EuroSCORE
4.7±3.4
4.4±3.2
IABP, % 1

14. Angiographic characteristics
Taxus
n=302
Cypher
n=305
LV ejection fraction, %
53.4±12.8
54.4±12.5
Coronary artery dominance
right
left
balanced 78 14 8 80 11 9
Trifurcation morphology, % 25 24
Occluded dominant RCA, % 15
LMCA size, mm
3.83±0.56
3.78±0.55

15. Left main lesion location
Ostial %
Midshaft
Distal
Taxus
n=302
Cypher
n=305

16. Stenting technique Culotte stenting T-stenting Single stenting Taxus%
Culotte stenting
T-stenting
Single stenting
Taxus
n=302
Cypher
n=305

17. 30-Day Clinical Outcome
P=.48
P=.66
P=.56
P=.57 %
Taxus
Cypher

18. 1-Year Clinical Outcome
P=.39
P=.83
P=.47 %
Taxus
Cypher

19. 1-Year Clinical Outcome (con‘t)
P=.71
P=.83 %
Taxus
Cypher

20. Pnoninferiority Taxus vs. Cypher<.001
Primary Endpoint: 1-Year MACE
RR 0.85; 95% CI 0.56 to 1.28 4
- 2 2 -4 6 8
- 2.2% + 95% CI = 2.7%
Pre-specified margin 8%
Difference in MACE
Pnoninferiority Taxus vs. Cypher<.001 %
Taxus
Cypher
MACE at 1 year

21. Primary Endpoint in Different Subgroups
Taxus
Cypher
Relative Risk
(95% CI)
P Value
for Interaction
No. of Events/Total (%)
Diabetes
Cypher better
Taxus better 2 1
0.41
Yes
12/90 (13.3)
17/86 (19.8) No
29/212 (13.6)
31/219 (14.1)
0.47
Parsonnet score
>15
10/106 (9.4)
13/89 (14.6)
≤15
23/193 (11.9)
25/216 (11.6)
0.36
EUROScore ≥6
24/112 (21.4)
24/97 (24.7)
<6
17/190 (8.9)
24/208 (11.5)

22. Secondary Endpoint: Angiographic Restenosis%
Taxus
Cypher

23. 2-Year Target Lesion Revascularization
P=.47 %
Taxus
Cypher

24. 2-Year Stent Thrombosis%
Definite stent thrombosis
Probable stent thrombosis
Taxus
Cypher

25. Years after randomization
Mortality 50 40
RR 1.14 (95% CI, ), P=.64 30
Cumulative Incidence, % 20
Taxus 10
Cypher 1 2
Years after randomization
Patients at Risk
Taxus
302
294
276
215
186
Cypher
305
293
280
225
201

26. Years after randomizationB
Death, Myocardial Infarction or Reintervention 50 40
RR 0.99 (95% CI, ), P=.96 30
Cumulative Incidence, %
Cypher 20
Taxus 10 1 2
Patients at Risk
Years after randomization
Taxus
302
278
250
189
160
Cypher
305
271
252
198
176

27. Summary
Treatment of unprotected LMCA lesions in unselected patients with DES is feasible, safe and effective up to two years
Both Taxus and Cypher stents provide similar clinical and angiographic outcomes in this form of coronary artery disease