GENNARO SARDELLA MD, FACC ,FESC
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rino.sardella@uniroma 1.it GENNARO SARDELLA MD, FACC ,FESC O.U. of Interventional Cardiology Dept. of Cardiovascular and Pulmonary Sciences Policlinico Umberto I “Sapienza “ University of ROME [email protected] On behalf of SMILE TRIAL investigators Impact of one Stage compared with Multistaged percutaneous complete coronary revascularIzation on cLinical outcome in multivessel NSTEMI patiEnts. (NCT01478984) Featured Clinical Research II
description
TRIAL. SMILE. Featured Clinical Research II. Impact of one S tage compared with M ultistaged percutaneous complete coronary revascular I zation on c L inical outcome in multivessel NSTEMI pati E nts. ( NCT01478984). On behalf of SMILE TRIAL investigators. - PowerPoint PPT Presentation
Transcript of GENNARO SARDELLA MD, FACC ,FESC
GENNARO SARDELLA MD, FACC ,FESC
O.U. of Interventional Cardiology Dept. of Cardiovascular and Pulmonary Sciences
Policlinico Umberto I “Sapienza “ University of ROME
On behalf of SMILE TRIAL investigators
Impact of one Stage compared with Multistaged percutaneous complete coronary revascularIzation on
cLinical outcome in multivessel NSTEMI patiEnts. (NCT01478984)
Featured Clinical Research II
Disclosure Statement of Financial Interest
• Grant/Research Support• Consulting Fees/Honoraria
• Major Stock Shareholder/Equity• Royalty Income• Ownership/Founder• Intellectual Property Rights• Other Financial Benefit
• None• Boston Scientific, Astra
Zeneca,Alvimedica,Biosensors,Terumo • None• None• None• None• None
Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
Multi-vessel Disease in the setting of ACS
30-40% in the setting of STEMIMuller DW, et al Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Am Heart J 1991;121:1042-9
Toma M,, et al. Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial. European Heart Journal 2010;31:1701-7
44-60% in the setting of NSTEMIEffects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia. Circulation1994;89:1545–1556.Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators.Lancet 1999;354:708–715.
Multi-vessel Disease in the setting of ACS
Culptit lesion uncertain and misleading
No suggestions
Guidelines and Multi-Vessels NSTEMI Patients
No References
•The strategy of multivessel stenting for
suitable significant stenoses rather than
stenting the culprit lesion only has not
been evaluated appropriately in a
randomized fashion
OBJECTIVE: The aim of our study is to compare one stage (S-PCI) vs multi-
staged (MS-PCI) complete coronary revascularization during the index
hospitalization in NSTEMI patients with > 1 vessel > 70% angiographically.
OBJECTIVE: The aim of our study is to compare one stage (S-PCI) vs multi-
staged (MS-PCI) complete coronary revascularization during the index
hospitalization in NSTEMI patients with > 1 vessel > 70% angiographically.
Impact of one Stage compared with Multistaged percutaneous complete coronary revascularIzation on cLinical outcome in
multivessel NSTEMI patiEnts.
HYPOTHESIS: HYPOTHESIS: Complete coronary revascularization, in multivessel Complete coronary revascularization, in multivessel NSTEMI patients, is superior to NSTEMI patients, is superior to ad hoc ad hoc culprit lesion PCIculprit lesion PCI
Statistical Analysis
• On the basis of a two-sided test size of 5% and a power of 80%, it was calculated that a minimum of 247 patients would need to be recruited in each group to detect a difference in the incidence of MACCE at one year of 9%. .
• Expected MACCE at 1 year * **
Multi-staged = 9% One Staged = 18%
• Applying the Pocock group sequential design for a trial with two planned analyses (the first after half the number of patients were recruited) would assume P<0.029 as a stopping rule at each analysis for a treatment difference.
*Shishehbor MH, et al. J Am Coll Cardiol 2007;49:849–854.**Kornowski R, Mehran R, Dangas G, et al. JACC 2011; 58 (7): 704-11
• DESIGN: Prospective, randomized, open label,double-arm, multi-center study
Primary Endpoint: Incidence of major adverse cardiac and cerebrovascular events (MACCE) defined as cardiac or non-cardiac death, re-infarction, re-hospitalization for acute coronary syndrome,repeat coronary revascularization and stroke 1 year.
Secondary endpoint : Incidence of
Bleedings at 30 days, 6 months and 1 year
• DESIGN: Prospective, randomized, open label,double-arm, multi-center study
Primary Endpoint: Incidence of major adverse cardiac and cerebrovascular events (MACCE) defined as cardiac or non-cardiac death, re-infarction, re-hospitalization for acute coronary syndrome,repeat coronary revascularization and stroke 1 year.
Secondary endpoint : Incidence of
Bleedings at 30 days, 6 months and 1 year
Study Design
500 NSTEMI pts 500 NSTEMI pts
SINGLE stage PCI revascularization
n= 253
SINGLE stage PCI revascularization
n= 253
Multi- stage PCI revascularization
n= 247
Multi- stage PCI revascularization
n= 247
Clinical Follow-Up (1 -6 -12Months)Clinical Follow-Up (1 -6 -12Months)
Angio> 1 vessel with > 70% DS
Angio> 1 vessel with > 70% DS
1:1 Randomization1:1 Randomization
Early Invasive Strategy (within 24 hrs) Early Invasive Strategy (within 24 hrs)
PoliclinicoUmberto I Rome
G.Sardella MDM.Mancone MDM.Pennacchi MDL.Lucisano MD
S.Giovanni Bosco Hospital Turin
R.Garbo MDF.Ugo MDG.Boccuzzi MD
P.I. : Gennaro Sardella MD
Steering Committe: M.Mancone,R.GarboL.Lucisano, M.Pennacchi
Safety Committee: U.Fabrizio,G.Boccuzzi
METHODS
age ≥ 18 years,
diagnosis of NSTEMI according to
current guidelines
MV disease at angio (> 1 vessel with
> 70% stenosis)
The unculprit vessel
should be a major (>2mm)
epicardial coronary artery or
branch (>2mm) and be suitable
for stent implantation.
signed informed consent.
Exclusion CriteriaInclusion Criteriacardiogenic shock or any condition requesting an Urgent Invasive Strategy (< 2hrs)left main coronary artery disease, CTO Syntax Score > 32previous coronary artery bypass grafting
surgery, candidate to by-pass surgery, severe valvular heart disease kidney impairment
FLOW-Chart
615 Multivessel pts(56,3%)
615 Multivessel pts(56,3%)
542 pts randomized542 pts randomized
73 pts excluded :5 pts left main coronary artery disease, 55 Syntax Score >32 and/or indication to CABG revascularization3 pts severe valvular heart disease 10 refused consent
73 pts excluded :5 pts left main coronary artery disease, 55 Syntax Score >32 and/or indication to CABG revascularization3 pts severe valvular heart disease 10 refused consent
27 unsuccessful complete coronary revascularization
15 pts were lost to the follow-up
27 unsuccessful complete coronary revascularization
15 pts were lost to the follow-up
SINGLE stage PCI revascularization n= 253
MACCE at 12 months analyzed
SINGLE stage PCI revascularization n= 253
MACCE at 12 months analyzed
Multi- stage PCI revascularization n= 247
MACCE at 12 months analyzed
Multi- stage PCI revascularization n= 247
MACCE at 12 months analyzed
Between September 2011 and August 2013 1091 pts with diagnosed NSTEMI
were scheduled.
Between September 2011 and August 2013 1091 pts with diagnosed NSTEMI
were scheduled.
476 pts excluded :143 pts suitable for EIS (< 2hrs)30 pts previous coronary artery
bypass grafting surgery 303 pts with a single lesion
476 pts excluded :143 pts suitable for EIS (< 2hrs)30 pts previous coronary artery
bypass grafting surgery 303 pts with a single lesion
Characteristics SINGLE Staged (tot. = 253) MULTI Staged (tot. =247) p value
Mean Age - yr 69.48 ± 11.36 69.95 ± 11.79 0.64
Sex – no. (%) Male Female
200 (79.05)53 (20.94)
198 (80.16)49 (19.84)
0.82
Medical History – no. (%) Diabetes NID Diabetes ID Hypertension Hypercholesterolemia Smoking Status Family History Prior MI Prior PCI Prior CABG
87 (34.38)6 (2.37)190 (75.09)147 (58.10)118 (46.64)134 (52.96)71 (28.06)39 (15.41)21 (8.30)
91 (36.84)9 (3.64)171 (69.23)139 (56.28)101 (40.89)131 (53.04)58 (23.48)40 (16.19)20 (8.10)
0.570.440.160.710.201.000.260.901.00
Mean Serum Creatinine – mg/dL 1.02 ± 0.32 1.03 ± 0.43 0.76
Troponin - ng/ml 0.55±1.40 0.45±1.31 0.41
Mean GRACE Death in Hospital score 180.27 ± 30.63 179.85 ± 31.41 0.87
Mean CRUSADE score 23.60 ± 10.49 23.45 ± 11.94 0.87
Mean Systolic Blood Pressure - mmHg 127.60 ± 10.66 126.80 ± 16.51 0.80
Mean Heart rate - bpm 79.88 ± 12.17 77.98 ± 12.36 0.07
Mean Left ventricle Ejection Fraction - % 47.26 ± 9.44 46.81 ± 10.57 0.61
Killip class – no. (%) III IV
6 (2.43)2 (0.81)
1 (0.40) 7 (2.83)
0.120.17
Baseline Characteristics
Therapy SINGLE Staged (tot. = 253) MULTI Staged (tot. = 247) p valueThienopyridines pre-randomization Clopidogrel 75 mg Clopidogrel 300 mg Clopidogrel 600 mg Prasugrel 60 mg Prasugrel 5 mg Ticagrelor 90 mg Ticagrelor 180 mg
42 (16.66)49 (19.36)53 (20.94)2 (0.79)0 106(41.89)1 (0.39)
21 (8.50)55 (22.26)60 (24.29)4 (1.62)2 (0.81)102 (41.29)3 (1.21)
0.64
Gp IIb/IIIa Inhibitors – no. (%) None Abciximab Tirofiban Eptifibatide
219 (86.56)10 (3.95)12 (4.74)12 (4.74)
214 (86.64)9 (3.64)13 (5.26)11 (4.45)
0.47
Thienopyridines post-procedure Clopidogrel 75 mg Prasugrel 10 mg Prasugrel 5 mg Ticagrelor 90 mg
109 (43.08)2 (0.79)0140 (55.33)
105 (42.51)4 (1.62)2 (0.81)136 (55.06)
0.71
Anti-aggregation therapy at Hospitalization
Characteristics SINGLE Staged (tot. =253)
(A)
MULTI Staged (tot. =247)First procedure
(B)
p valueA vs. B
MULTI Staged (tot. =247)Second
procedure (C)
p valueA vs. C
Access site – no. (%)
Right femoral Left femoral Right radial Left radial
43 (16.99)1 (0.39)7 (2.76)202 (79.84)
29 (11.74)6 (2.43)15 (6.07)197 (89.75)
0.090.060.081.00
75 (30.36)2 (0.81)41 (16.60)129 (52.23)
0.00051.0<0.0001<0.0001
Artery access site
Characteristics SINGLE Staged (tot. =253) MULTI Staged (tot. =247) P value
Target vessel – n. (%) Left anterior descending Right coronary artery Left circumflex Left main
225 (36.88) 152 (24.92)209 (34.26)24 (3.93)
223 (36.67) 157 (25.82)201 (33.05)13 (2.13)
0.61
Mean number of treated vessels
2.41 ± 0.37 2.46 ± 0.67 0.30
Lesion Type – n. (%) A B1 B2 C
87 (11.90)199 (27.22)185 (25.31)260 (35.57)
76 (10.55)180 (25.00)189 (26.25)275 (38.19)
0.37
Baseline angiographic analysis Mean DVR – mm Mean Lesion Length – mm Mean MLD – mm Diameter stenosis - % FFR/IVUS utilization %
2.91 ± 0.4222.75 ± 12.720.84 ± 0.5284.48 ± 14..4510,6
2.87 ± 0.3923.43 ± 16.400.81 ± 0.6286.06 ± 12.2518,6
0.260.600.550.180. 32
Mean Syntax Score 15.77 ± 3.96 15.26 ± 7.73 0.34Mean TIMI flow pre-procedure 2.70 ± 0.71 2.79 ± 0.69 0.15Stents per patient 3.07 ± 1.37 3.14 ± 1.44 0.58Stent type – no. (%) Bare Metal Biolimus Zotarolimus Everolimus POBA
135 (17.26)297 (37.97)38 (4.85)306 (39.13)6 (0.76)
139 (17.93)295 (38.06)40 (5.16)294 (37.93)7 (0.90)
0.65
Mean Minimum stent diameter - mm
2.95 ± 0.41
2.90 ± 0.63
0.28
Mean cumulative stent length – mm
23.04 ± 15.50
24.46 ± 20.60
0.38
Procedural characteristics
Characteristics SINGLE Staged (tot. =253)
MULTI Staged (tot. =247)First procedure
MULTI Staged (tot. =247)Second procedure
P valueSingle vs Multi 1st procedure
P valueSingle vs Multi 2nd
procedure
CK-MB Pre 9.58±13.34 10.66±11.82 0.33
Troponin Pre 0.55±1.40 0.45±1.31 0.41
Myoglobin pre 111.09±250.06 91.02±82.56 0.4337
Post ProcedureCK-MB Post 9.82±24.64 10.61±12.72 10.91±11.66 0.6545 0.5300
Troponin Post 0.54±0.96 0.95±1.28 0.60±0.83 ˂0.0001 0.4578
Myoglobin post 79.31±129.73 80.19±58.86 59.81±34.88 0.9227 0.0230
Myocardial Enzymes
p=ns
p<0.001
p=ns
In-Hospital Clinical Events
Characteristics SINGLE Staged (tot. =253) MULTI Staged (tot. =247) P valueMACCE – no. (%)Death – no. (%)Cardiac Death – no. (%)
Stroke – no.(%)Myocardial Infarction *
Q – no. (%)non-Q – no. (%)
UA needing HospitalizationTVR – no. (%)
1 (0.39)0 0 01 (0.39)01 (0.39)01 (0.39)
3 (1.21)2 (0.80)0 01 (0.40)01 (0.40)01 (0.40)
0.360.450.681.001.001.001.001.001.00
Definite Stent thrombosis 1 (0.39) 1 (0.40) 1.0Bleedings – no. (%) Minimal Minor Major
0 1 (0.39)0
6 (2.42)1 (0.40)0
0.011.01.0
* Excluded peri-procedural MI
1 month Clinical Events
Characteristics SINGLE Staged (tot. =253) MULTI Staged (tot. =247) P value
MACCE – no. (%)Death – no. (%)Cardiac Death – no. (%)
Stroke – no.(%)Myocardial Infarction Q – no. (%)non-Q – no. (%)
UA needing HospitalizationTVR – no. (%)
6 (2.37)5 (1.97)4 (1.58)01 (0.39)01 (0.39)2 (0.78)4 (1.58)
3 (1.21)2 (0.88)2 (0.88)01 (0.40)01 (0.40)1 (0.40)4 (1.61)
0.500.450.681.001.001.001.001.001.00
Definite Stent thrombosis 1 (0.39) 1 (0.39) 1.0
Bleedings – no. (%) *
1 (0.39)
7 (2.82)
0.01
*According to BARC Criteria * Mehran R, Circulation. 2011;123:2736-2747.
6 months Clinical Events
Characteristics SINGLE Staged (tot. =253) MULTI Staged (tot. =247)
P value
MACCE – no. (%)Death – no. (%)Cardiac Death – no. (%)
Stroke – no.(%)Myocardial Infarction Q – no. (%)non-Q – no. (%)
UA needing HospitalizationTVR – no. (%)
13 (5.13)8 (3.16)6 (2.37)04 (1.58)04 (1.58)5 (1.97)9 (3.55)
27 (10.93)19 (7.69)10 (4.04)07 (2.83)2 (0.80)5 (2.02)4 (1.61)13 (5.26)
0.020.020.311.000.370.240.741.000.51
Definite Stent thrombosis 1 (0.39) 1 (0.40) 1.00Bleedings – no. (%)
1 (0.39)
8 (3.22)
0.01
Characteristics SINGLE Staged (tot. =253) MULTI Staged (tot. =247)
P value
MACCE – no. (%)Death – no. (%)Cardiac Death – no. (%)
Stroke – no.(%)Myocardial Infarction Q – no. (%)non-Q – no. (%)
UA needing Hospitalization
TVR – no. (%)
33 (13.04)14 (5.53)9 (3.55)1 (0.39)7 (2.76)2 (0.78)5 (1.98)11 (4.34)22 (8.69)
57 (23.07)28 (11.33%)13 (5.26%)09 (3.64)3 (1.21)6 (2.42)13 (5.26)36 (14.57%)
0.00360.020.3810.610.680.760.670.05
Definite Stent thrombosis 1 (0.39) 1 (0.40) 1.00Bleedings – no. (%)
4 (1.56)
12(4.85)
0.03
12 months Clinical Events
12 months follow-up Survival Analysis
MACCE One-stage rev.
Multi-stage rev.
Time (days)
Cum
MAC
CE
p log rank =0.004
12 months follow-up Survival Analysis Non- Cardiac Death
One-stage rev.
Multi-stage rev.
Time (days)
Cum
Non
-Car
diac
Dea
th
p log rank =0.021
12 months follow-up Survival Analysis
Target Vessel Revascularization One-stage rev.
Multi-stage rev.
Time (days)
Cum
TVR
p log rank =0.045
12 months follow-up Survival Analysis
Cardiac Death One-stage rev.
Multi-stage rev.
Time (days)
Cum
Car
diac
Dea
th
p log rank =0.361
12 months follow-up Survival Analysis MACCE (cardiac death only)
One-stage rev.
Multi-stage rev.
p log rank =0.060
Time (days)
Card
iac
deat
h
Conclusions
•One staged complete coronary revascularization is associated:• to less minor bleeding • a rapid decrease of myocardial enzymes in particular troponin• to minor incidence of MACCE
• The superiority of one staged complete coronary revascularization in terms of MACCE is mainly due to the unexplained higher incidence of non cardiac death.
• One staged revascularization is associated to a lower TVR rate.
Positive Features of SMILE TRIAL
Positive Features of SMILE TRIAL
Limitations of SMILE TRIAL
Limitations of SMILE TRIAL
12 months follow-up: Survival Analysis non-Q MI
One-stage population
Multi-stage population
Time (days)
Cum
non
-Q M
I
p log rank =0.734
12 months follow-up Survival Analysis
Q MI One-stage population
Multi-stage population
Time (days)
Cum
Q M
I
p log rank =0.636
12 months follow-up Survival Analysis STROKE
One-stage population
Multi-stage population
Time (days)
Cum
STR
OKE
p log rank =0.550
