LONG-TERM EVENTS IN SIROLIMUS-ELUTING STENTS: a specific focus on diseased saphenous vein grafts...
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LONG-TERM EVENTS IN SIROLIMUS-ELUTING STENTS:LONG-TERM EVENTS IN SIROLIMUS-ELUTING STENTS:
a specific focus on diseased saphenous vein grafts a specific focus on diseased saphenous vein grafts from the randomized DELAYED-RRISC trialfrom the randomized DELAYED-RRISC trial
Pierfrancesco Agostoni, MDPierfrancesco Agostoni, MD
On behalf of the On behalf of the DELAYED-RRISC DELAYED-RRISC ((DDeath and eath and EEvents at vents at LLong-term ong-term follow up follow up AAnalnalYYsis: sis: EExtended xtended DDuration of the uration of the RReduction of eduction of
RRestenosis estenosis IIn n SSaphenous vein grafts with aphenous vein grafts with CCypher stentypher stent)) Investigators Investigators
Antwerp Cardiovascular Institute MiddelheimAntwerp Cardiovascular Institute MiddelheimAntwerp, BelgiumAntwerp, Belgium
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RRISC TrialReduction of Restenosis In
Saphenous vein grafts with Cypher stent
• Prospective, randomized, double-blind, non industry sponsored, single center, trial comparing SES vs. BMS in SVG lesions
• 75 patients with 96 lesions localized in 80 diseased SVG were included
• Enrollment: September 2003-November 2004
• Primary endpoint : 6-month in-stent late loss
• Secondary endpoints (all at 6 months follow up): – Binary angiographic restenosis (in-stent/in-segment)– Clinical events (death, MI, TLR, TVR)
Vermeersch, Agostoni et al. JACC 2006
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• Major Inclusion Criteria• De novo lesion (stenosis >50%) in a diseased SVG• Diameter ranging between 2.5 and 4.0 mm• Diagnosis of angina pectoris
Osial stenoses & thrombotic/calcific stenoses were allowedNo maximum lesion length prespecified
• Major Exclusion Criteria• Impaired renal function • Prior stent within 5 mm of target lesion• Totally occluded vein grafts• Documented LV Ejection Fraction <25%• Distal anastomotic stenosis • Prior brachytherapy in the index vessel• Recent MI (<7 days)
RRISC TrialReduction of Restenosis In
Saphenous vein grafts with Cypher stent
Vermeersch, Agostoni et al. JACC 2006
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75 patients (with 96 lesions) meeting the inclusion criteria
37 patients (49 lesions) randomized to BMS
38 patients (47 lesions) randomized to SES
37 patients (49 lesions) available for 6-month angiographic follow up
35 patients (44 lesions) available for 6-month angiographic follow up
1 patient died2 patients refused angio follow up
randomization
No patient was lost to follow up. All patients, but 1 (dead) available for 6-month clinical follow up.
204 patients screened(September 2003-November 2004)
Patients excluded (reason):2 patients (age >85 years)18 patients (acute MI)7 patients (MI within the last 7 days)3 patients (creatinine >3 mg/dL)40 patients (vein graft with RVD >4.0 mm)12 patients (distal anastomotic disease)38 patients (restenotic lesions)8 patients (enrolled in other trials)1 patient (no informed consent)
Vermeersch, Agostoni et al. JACC 2006
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BMS(n=37)
SES(n=38)
P-value
Age (years) 72 ± 8 73 ± 7 0.36Men 33 (89%) 31 (82%) 0.36Family history 29 (78%) 25 (66%) 0.23Hypertension 21 (57%) 22 (58%) 0.84Hypercholesterolemia 31 (84%) 33 (87%) 0.74Current smoker 4 (11%) 2 (5%) 0.46Diabetes Mellitus 5 (14%) 6 (16%) 0.78Body mass index (Kg/m2) 26.4 ± 3.9 26.4 ± 3.1 0.97History of heart failure 7 (19%) 6 (16%) 0.72Prior myocardial infarction 15 (41%) 17 (45%) 0.71Prior coronary angioplasty 15 (41%) 12 (32%) 0.42Unstable angina pectoris 19 (51%) 23 (60%) 0.41Ejection Fraction (%) 72 ± 12 68 ± 18 0.37Age of the grafts (years) 12.6 ± 5.9 12.4 ± 4.6 0.92
Baseline characteristics
Vermeersch, Agostoni et al. JACC 2006
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BMS(lesions=49)
SES(lesions=47)
P-value
Degenerated saphenous vein grafts 17 (41.5%) 19 (48.7%) 0.51Recipient native vessel territory 0.11
Left anterior descending/diagonal 6 (12.2%) 9 (19.2%)
Circumflex/obtuse marginal 26 (53.1%) 15 (31.9%)
Right coronary artery 17 (34.7%) 23 (48.9%)
Angiographic evidence/suspect of thrombus 12 (24.5%) 17 (36.2%) 0.21Moderately/heavily calcified lesions 9 (18.4%) 8 (17%) 0.86Number of stents per patient 1.46 ± 0.7 1.58 ± 0.7 0.45Number of stents per lesion 1.11 ± 0.3 1.28 ± 0.5 0.14Total stent length per patient (mm) 33.4 ± 18.2 36.9 ± 17.6 0.39Total stent length per lesion (mm) 25.2 ± 11.9 29.9 ± 15.6 0.11Stent diameter (mm) 3.36 ± 0.26 3.41 ± 0.19 0.72Successful direct stenting 44 (89.8%) 44 (93.6%) 0.50Post-dilatation 7 (14.3%) 14 (29.8%) 0.09Maximal balloon diameter (mm) 3.44 ± 0.38 3.56 ± 0.37 0.09Maximal inflation pressure (atm) 18.8 ± 2.2 18.7 ± 2.8 0.85Vermeersch, Agostoni et al. JACC 2006
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0.20
0.40
0.60
0.80
1.00
0.17 0.17 0.79 0.38 0.24 0.19
p=0.001
p=0.9 p=0.6
0.70 0.41
p=0.01
Prox edge Dist edgeIn-stent In-segment
Late Loss Analysis
Vermeersch, Agostoni et al. JACC 2006
BMSSES
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In-segment
10
20
30
40
11.4%30.6% 13.6%32.7%
p=0.024 p=0.031
In-stent
Δ=19.1%RRR=0.58
Δ=19.2%RRR=0.63
BMSSES
Binary Restenosis
Vermeersch, Agostoni et al. JACC 2006
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6-month MACE
BMSn=3737
SESn=3838 P value
In-hospitalDeath 0 0Repeat revascularization 0 0Periprocedural MI 1 (2.7%) 2 (5.3%) 0.99
Between discharge and 6 monthsDeath 0 1 (2.6%) 0.99Myocardial infarction 0 1 (2.6%) 0.99TLRTLR (per-patient) 8 (21.6%) 2 (5.3%) 0.0470.047TVRTVR (per-patient) 10 (27%) 2 (5.3%) 0.0120.012
Cumulative 6-month MACE 11 (29.7%) 6 (15.8%) 0.15
- Due to safety issues recently raised with DES(ESC/WCC 2006), we decided to further follow upour patients, in order to analyze long-term events.
-In September 2006, a new approval was obtainedfrom the local Ethics Committee to extend the follow-up.
-A new informed consent was obtained fromall the patients.
-All patients were contacted between Septemberand December 2006 (no lost to follow up).
-Blinding was maintained for patients andreferring physicians/cardiologists.
Vermeersch, Agostoni et al. JACC 2006
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BMSn=3737
SESn=3838 P value
Death 0 10 (26.3%) 0.001
Myocardial infarction 1 (2.7%) 4 (10.5%) 0.35
TLR 3 (8.1%) 7 (18.4%) 0.30
TVR 4 (10.8%) 11 (28.9%) 0.05
MACE after 6-monthup to 32 months (median f.u.)
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BMSn=3737
SESn=3838 P value
Death 0 11 (28.9%) <0.001Myocardial infarction 2 (5.4%) 7 (18.4%) 0.15TLR 11 (29.7%) 9 (23.7%) 0.55TVR 14 (37.8%) 13 (34.2%) 0.74MACE 15 (40.5%) 22 (57.9%) 0.13
Other PCI (not TLR/TVR) 14 (37.8%) 12 (31.6%) 0.57Double anti-platelet therapy 19 (51.4%) 19 (50%) 0.91Single anti-platelet therapy 14 (37.8%) 15 (39.5%) 0.88No anti-platelet therapy 4 (10.8%) 4 (10.5%) 0.97Statin therapy 27 (73%) 29 (76.5%) 0.74
Cumulative MACE
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Stent Thrombosis(ARC criteria)
BMSn=3737
SESn=3838 P value
Definite 0 2 (5.2%)1 fatal at 13 months
1 non fatal at 30 months
0.49
Probable 0 0 -
Possible 0 3 (7.9%)1 sudden death at 7.5 months1 sudden death at 11.5 months1 sudden death at 35 months
0.30
Total 0 5 (13.1%) 0.054 Fisher Exact0.022 Log Rank
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Time Cause of death Anti-thrombotic therapy
5 months progressive heart failure TP7.5 months sudden out-of-hospital death TP, W
11.5 months sudden out-of-hospital death ASA, TP14.5 months progressive heart failure after MI due to
thrombosis of the index stent-
(suspended 1 week before MI for knee surgery)16 months metastatic urothelial carcinoma -
(stop 1 month before for severe anemia)19 months metastatic colon carcinoma -
(stop 2 months before for anorexia)22 months progressive MOF after peri-operative (limb ischemia) MI
(no stent thrombosis of the stent)-
(suspended 1 week before MI for AICD change)23.5 months post-operative (AVR and ReDo CABG
for progression of CAD) infectionASA, TP
30 months progressive Parkinson disease ASA, TP33 months progressive MOF after ReDo CABG
(documented in-stent restenosis)ASA, TP
35 months sudden out-of-hospital death ASA, TP
Causes of Death
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Conclusions• The use of BMS was associated with lower long-term mortality than the use of SES for SVG disease.
• Also the 6-month reduction in repeated revascularization procedures shown with the use of SES was lost at longer-term follow-up.
• However:• this is secondary post-hoc analysis,• the play of chance should be strongly considered,• “hidden” factors unrelated to stent type could have influenced the final results.
• Further studies are required before conclusions can be made about the safety or harm of using SES for SVG lesions.
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DELAYED-RRISC Investigators
Steering Committee: Pierfrancesco Agostoni, MD Paul Vermeersch, MD
Other Investigators: Stefan Verheye, MD, PhDGlenn Van Langenhove, MD, PhDFrank Van den Branden, MD
Paul Van den Heuvel, MDCarl Convens, MD
Data Monitoring: Christine Jacobs, RNNancy Aerts, RNAnne-Rose Gustin (Incubate, Cardiac Solutions)
CEC Committee: Giuseppe M. Sangiorgi, MDGiuseppe G.L. Biondi-Zoccai, MD
Statistical Analysis: Pierfrancesco Agostoni, MD