Transcript intranet.cardiol.br

Adjunctive Cilostazol Versus Double Dose
Clopidogrel After PCI with Drug Eluting Stent
: The HOST-ASSURE Randomized Trial
Hyo-Soo Kim, MD/PhD
Kyung-Woo Park, Si-Hyuck Kang, Kwang-Soo Cha,
Byoung-Eun Park, Jay-Young Rhew, Hui-Kyung Jeon, In-Ho Chae
On Behalf of The HOST-ASSURE Trial Investigators
Seoul National University Hospital, Seoul, Korea
Background
• Inhibition of platelet reactivity in the first month post-PCI is
critical in preventing thrombotic events.
• One-week duration of doubling the dose of clopidogrel was
shown to improve outcome at one month compared with
conventional dose in ACS patients undergoing PCI.
• Yet in Asia, the adjunctive use of cilostazol to dual
antiplatelet therapy (triple antiplatelet therapy, TAT) is
used more commonly than doubling the dose of
clopidogrel (double-dose dual antiplatelet therapy, DDAT)
in high-risk patients.
• However, there has been no large scale head-to-head
comparison of TAT with DDAT to date with regard to clinical
outcome.
Objectives
2x2 Factorial Design
Triple Antiplatelet
Therapy
(TAT)
PtCr-EES
(PromusTM
ElementTM)
vs.
Double-Dose
Clopidogrel Dual
Antiplatelet Therapy
(DDAT)
vs.
CoCr-ZES
(Endeavor®Resolute)
Objectives
2x2 Factorial Design
Triple Antiplatelet
Therapy
(TAT)
vs.
Double-Dose
Clopidogrel Dual
Antiplatelet Therapy
(DDAT)
[Hypothesis]
TAT is non-inferior to DDAT
regarding net clinical outcome at 1 month
Study Design
Prospective, single-blinded, randomized multi-center trial
3,750 All Comers Receiving PCI
40 Centers in Korea
2x2 Factorial Design
Aspirin 300 mg + Clopidogrel 300-600 mg Loading
PtCr-EES arm
(N=2,500)
Stent Arm
2:1 Randomization
CoCr-ZES arm
(N=1,250)
TAT arm
Anti-Platelet Arm
1:1 Randomization
DDAT arm
(N=1,875)
(N=1,875)
Percutaneous Coronary Intervention
200 mg Cilostazol Loading
No Cilostazol Loading
Aspirin 100 mg QD
Clopidogrel 75 mg QD
Cilostazol 100mg BID
Aspirin 100 mg QD
Clopidogrel 150 mg QD
Net Clinical Outcome at 1 Month Post-PCI (Intention-To-Treat Analysis)
Enrollment Criteria
General Inclusion Criteria
Exclusion Criteria
• Age ≥18 years
• Ability to verbally confirm understandings
of risks, benefits and treatment
alternatives with written informed consent
prior to any study-related procedure
• Significant lesion (>50% by visual
estimate) in any of the coronary arteries,
venous or arterial bypass grafts
• Evidence of myocardial ischemia
or diameter stenosis > 70%
• Known hypersensitivity/contraindication
to heparin, aspirin, clopidogrel, cilostazol,
everolimus, zotarolimus, or contrast
media
• Systemic (intravenous) Everolimus or
Zotarolimus use ≤ 12 months
• Female of childbearing potential
• History of bleeding diathesis, known
coagulopathy (including HIT), abnormal
CBC (Hb < 10 g/dL or PLT < 100k /μL) or
refusal of blood transfusions
• LVEF <25% or cardiogenic shock
• GI or GU bleeding ≤ 3 months
or major surgery ≤ 2 months
• Life expectancy <1 year
• Actively participating in another drug or
device investigational study
• Symptomatic heart failure
Angiographic Inclusion Criteria
• Target lesion in coronary artery, venous
or arterial bypass graft with diameter of ≥
2.5 mm and ≤ 4.25 mm
• Target lesion amenable for PCI
Study Endpoints
• Primary Endpoint: net clinical outcome at 1 month
(a composite of cardiac death, nonfatal MI, definite or probable ST,
stroke and PLATO major bleeding)
• Secondary Endpoints
–
–
–
–
–
–
–
Cardiac death, all-cause death
Nonfatal MI: periprocedural/spontaneous MI
ARC-defined ST: definite or probable ST, definite ST, probable ST
Stroke
PLATO major/minor bleeding
Target vessel revascularization (TVR)
Target lesion revascularization (TLR)
• Platelet Function Test: VerifyNow P2Y12 Assay
1) At 12-24 hours after loading of clopidogrel
2) At 1-month F/U under maintenance dose
Statistical Assumption
Non-inferiority Design for Primary Endpoint
(net clinical outcome at 1 month)
• Assumption
– 2% in TAT group
– 3% in DDAT group
• Non-inferiority Margin: 0.75% for Primary Endpoint
– Type I error (1-sided α): 2.5%
– Attrition rate: 2.5%
– Primary Analysis: Intention-to-treat analysis
– Statistical power >90% (β<0.10)
 N=3,750
Trial Coordination
Principal
Investigator
Hyo-Soo Kim
Executive
Committee
Hyo-Soo Kim, In-Ho Chae, Kwang Soo Cha,
Byoung Eun Park, Jay Young Rhew, Hui-Kyung Jeon
Data Management
Dream CIS Inc. (contract research organization)
Trial Coordination
Investigators at the Cardiovascular Clinical Research Center
at Seoul National University Hospital
Data Safety
Monitoring Board
Seung-Woo Park, Young-Jin Choi, Kwangil Kim
Clinical Event
Adjudication
Committee
Yong-Seok Kim, Sang Min Park, Nae Hee Lee
Participating Centers
40 Hospitals in Republic of Korea
Site
PI
Site
PI
Seoul National University Hospital
Kim, Hyo-Soo
Konyang University Hospital
Bae, Jang-Ho
Seoul National University Bundang Hospital
Chae, In-Ho
Hallym University Kangdong Sacred Heart Hospital
Han, Kyoo-Rok
Pusan National University Hospital
Cha, Kwang Soo
Ewha Womans University Mokdong Hospital
Park, Si-Hoon
Dankook University Hospital
Park, Byoung Eun
Korea University Guro Hospital
Rha, Seung-Woon
Presbyterian Medical Center
Rhew, Jay Young
Hallym University Sacred heart Hospital
Park, Woo-Jung
Uijeongbu St. Mary’s Hospital
Jeon, Hui-Kyung
Wongwang University Hospital
Oh, Seok-Kyu
Ulsan University Hospital
Shin, Eun Seok
Korea University Anam Hospital
Lim, Do-Sun
Samsung Changwon Hospital
Oh, Ju Hyeon
Kwangju Christian Hospital
Lee, Seung-Wook
Chonnam National University Hospital
Jeong, Myung-Ho
Hallym University Chuncheon Sacred Heart Hospital
Yoon, Duck-Hyoung
Chungbuk National University Hospital
Hwang, Kyung-Kuk
Kyung Hee University Hospital at Gangdong
Kim, Chong-Jin
Wonju Christian Hospital
Yoon, Jung-Han
Seoul Medical Center
Kim, Seok-Yeon
Inje University Ilsan Paik Hospital
Lee, Sung Yun
Gachon University Gil Hospital
Ahn, Taehoon
Boramae Medical Center
Kim, Sanghyun
Samsung Medical Center
Gwon, Hyeon-Cheol
Dong-A Medical Center
Park, Tae-Ho
Hallym University Kangnam Sacred Heart Hospital
Lee, Namho
Gangnam Severance Hospital
Kwon, Hyuck-Moon
National Health Insurance Medical Center
Jeon, Dong-Woon
St. Vincent’s Hospital
Moon, Keon Woong
Soonchunhyang University Hospital
Hyun, Min-Soo
Daegu Catholic University Medical Center
Ryu, Jae-Kean
Daejun Eulji University Hospital
Lee, Sang
Keimyung University Dongsan Medical Center
Hur, Seung-Ho
Hanyang University Guri Hospital
Lee, Jaewoong
Daegu Fatima Hospital
Lee, Bong-Ryul
Kangwon National University Hospital
Ryu, Dong Ryeol
Gyeongsang National University Hospital
Park, Yong-Whi
Kosin University Gospel Hospital
Cha, Tae-Joon
Trial Flow
3,755 Patients
Enrolled and Randomized
Allocated to TAT
(N=1,879)
49 Did not receive allocated treatment
4 Did not receive coronary stenting
4 Did not meet inclusion criteria
14 Patient decision
27 Other reasons
Received TAT as Randomized
(N=1,830)
109 Did not adhere to allocated treatment
4 Lost to follow-up
9 Cardiovascular events
14 Had bleeding
34 Had side effects
11 Voluntarily withdrawn or poorly compliant
18 At physicians’ discretion
19 Other reasons
Allocated to DDAT
(N=1,876)
146 Did not receive allocated treatment
7 Did not receive coronary stenting
11 Did not meet inclusion criteria
97 Patient decision
31 Other reasons
Received DDAT as Randomized
(N=1,730)
107 Did not adhere to allocated treatment
4 Lost to follow-up
17 Cardiovascular events
13 Had bleeding
8 Had side effects
9 Voluntarily withdrawn or poorly compliant
23 At physicians’ discretion
33 Other reasons
Adhered to TAT for 1 Month
(N=1,721)
Adhered to DDAT for 1 Month
(N=1,623)
1,879 Patients Analyzed
According to ITT
1,876 Patients Analyzed
According to ITT
Baseline Characteristics
TAT
DDAT
(N=1,879)
(N=1,876)
Age
62.8±10.7
63.7±10.9
Men
1,311 (69.8)
1,257 (67.0)
24.7±3.2
24.6±3.1
1,256 (66.8)
1,286 (68.6)
598 (31.8)
588 (31.3)
66 (3.5)
71 (3.8)
1,206 (64.2)
1,176 (62.7)
616 (32.8)
577 (30.8)
Chronic renal failure
42 (2.2)
50 (2.7)
Peripheral artery disease
44 (2.3)
24 (1.3)
Cerebrovascular disease
120 (6.4)
128 (6.8)
Previous PCI
188 (10.0)
181 (9.6)
Previous bypass surgery
11 (0.6)
15 (0.8)
Pervious MI
69 (3.7)
96 (5.1)
Previous CHF
23 (1.2)
31 (1.7)
Characteristic
Body mass index
Hypertension
Diabetes
insulin-requiring diabetes
Dyslipidemia
Current smoker
Baseline Characteristics
TAT
DDAT
(N=1,879)
(N=1,876)
96 (5.1)
86 (4.6)
Stable angina
564 (30.0)
549 (29.3)
Unstable angina
690 (36.7)
688 (36.7)
NSTEMI
328 (17.5)
332 (17.7)
STEMI
201 (10.7)
221 (11.8)
Left ventricular ejection fraction (%)
60.3±10.3
59.9±10.3
Hemoglobin (g/dL)
13.7±1.8
13.7±1.7
Platelet count (x103/mm)
227±63
227±61
Serum creatinine (mg/dL)
1.0±0.8
1.0±0.8
Total cholesterol (mg/dL)
178±44
177±44
Triglyceride (mg/dL)
143±93
136±95
HDL-cholesterol (mg/dL)
44±12
44±11
LDL-cholesterol (mg/dL)
110±42
109±38
Characteristic
Clinical diagnosis
Slient ischemia
Baseline laboratory findings
Baseline Characteristics
TAT
DDAT
(N=1,879)
(N=1,876)
Aspirin
1,867 (99.4)
1,862 (99.3)
Clopidogrel
1,866 (99.3)
1,863 (99.3)
β-blocker
1,277 (68.0)
1,277 (68.1)
357 (19.0)
407 (21.7)
ACE inhibitor or ARB
1,215 (64.7)
1,248 (66.5)
CYP3A4-metabolized statin*
1,032 (54.9)
1,060 (56.5)
Non-CYP3A4-metabolized statin**
545 (29.0)
559 (29.8)
Proton pump inhibitor
153 (8.1)
148 (7.9)
Characteristic
Medications at discharge
Calcium channel blocker
*CYP3A4-metabolized statin: simvastatin, lovastatin, atorvastatin, etc
**Non-CYP3A4-metabolized statin: rosuvastatin, pravastatin, pitavastatin, fluvastatin
Angiographic & Procedural Characteristics
Characteristic
Angiographic disease extent
1-vessel disease
2-vessel disease
3-vessel disease
Number of lesions treated per patient
Stent arm – intention-to-treat
Promus-Element arm
Endeavor-Resolute arm
Type of drug-eluting stents – per protocol
No stents used
Promus-Element
Endeavor-Resolute
Others
Number of stents per patient
Use of IVUS or OCT
Treatment of left main disease
Treatment of bifurcation lesions
Use of glycoprotein IIb/IIIa inhibitors
TAT
DDAT
(N=1,879)
(N=1,876)
P Value
0.631
856 (45.6)
618 (32.9)
405 (21.6)
1.5±0.8
877 (46.7)
590 (31.4)
409 (21.8)
1.5±0.8
1,253 (66.7)
626 (33.3)
1,250 (66.6)
626 (33.4)
0.639
0.972
0.552
14 (0.7)
1,198 (63.8)
587 (31.2)
80 (4.3)
1.6±0.9
737 (39.2)
57 (3.0)
308 (16.4)
46 (2.4)
9 (0.5)
1,202 (64.1)
573 (30.5)
92 (4.9)
1.6±0.9
763 (40.7)
55 (2.9)
303 (16.2)
50 (2.7)
0.513
0.365
0.852
0.842
0.673
Primary Endpoint
Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
Cumulative Incidence of
Primary Endpoint (%)
4
Non-inferiority P<0.001
Superiority P=0.566
3
2
DDAT: 1.4%
1
TAT: 1.2%
0
0
7
14
21
28
35
Days after Randomization
No. at Risk
TAT
1,879
1,855
1,845
1,832
1,763
1,538
DDAT
1,876
1,848
1,836
1,820
1,764
1,525
Landmark Analysis
Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
Cumulative Incidence of
Primary Endpoint (%)
1.5
Overall P=0.565
P=0.566
1.0
P=0.343
DDAT
0.5
TAT
0.0
0
7
14
21
28
35
Days after Randomization
No. at Risk
TAT
1,879
1,855
1,845
1,832
1,763
1,538
DDAT
1,876
1,848
1,836
1,820
1,764
1,525
Primary Endpoint
Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
Non-inferiority
P=0.005
TAT
DDAT
(N=1,879)
(N=1,876)
23 (1.22%)
27 (1.44%)
Predefined margin
: 0.75%
Absolute Risk Difference: -0.22%
(standard error: 0.37%)
Upper 1-sided 97.5% CI: 0.52%
-0.5
0.0
0.5
1.0
Risk Difference with 1-sided 97.5% CI
(TAT-DDAT)
Landmark Analysis
Primary Endpoint
1.0
P=0.343
DDAT
0.5
TAT
1.5
Overall P=0.797
1.0
DDAT
TAT
0.5
P=0.801
P=0.998
Cumulative Incidence (%)
Overall P=0.565
P=0.566
Cumulative Incidence (%)
0.0
0
7
14
21
28
35
1.0
DDAT
TAT
P=0.179
0.5
P=0.563
7
14
21
28
35
0
7
14
21
28
35
Days after Randomization
Days after Randomization
Days after Randomization
Stroke
Definite/Probable ST
PLATO Major Bleeding
1.5
1.0
DDAT
TAT
0.5
P=0.157
P=0.659
0.0
Cumulative Incidence (%)
1.5
Overall P=0.654
1.5
Overall P=0.365
1.0
DDAT
TAT
0.5
P=0.256
P=0.391
0.0
0
Overall P=0.178
0.0
0
7
14
21
28
Days after Randomization
35
Cumulative Incidence (%)
Cumulative Incidence (%)
1.5
0.0
Cumulative Incidence (%)
Nonfatal MI
Cardiac Death
1.5
Overall P=0.999
1.0
DDAT
TAT
0.5
P=0.999
P=0.999
0.0
0
7
14
21
28
Days after Randomization
35
0
7
14
21
28
Days after Randomization
35
Clinical Outcomes
Event Rates at D/C
End point
Primary end point
Secondary end points
Cardiac death
Nonfatal MI
Periprocedural MI
Spontaneous MI
Stroke
Ischemic stroke
ST, definite or probable
ST, definite
ST, probable
PLATO major bleeding
Other events
All-cause death
PLATO minor bleeding
TLR
TVR
Event Rates at 1 Month
Hazard Ratio
(95% CI)
P
TAT
(N=1,879)
DDAT
(N=1,876)
TAT
(N=1,879)
DDAT
(N=1,876)
16 (0.9)
17 (0.9)
23 (1.2)
27 (1.4)
0.85 (0.49-1.48) 0.566
6 (0.3)
6 (0.3)
6 (0.3)
0 (0.0)
2 (0.1)
2 (0.1)
2 (0.1)
1 (0.1)
1 (0.1)
3 (0.2)
5 (0.3)
8 (0.4)
8 (0.4)
0 (0.0)
3 (0.2)
3 (0.2)
2 (0.1)
0 (0.0)
2 (0.1)
4 (0.2)
8 (0.4)
7 (0.4)
6 (0.3)
1 (0.1)
2 (0.1)
2 (0.1)
4 (0.2)
2 (0.1)
2 (0.1)
8 (0.4)
7 (0.4)
13 (0.7)
8 (0.4)
5 (0.3)
3 (0.2)
3 (0.2)
7 (0.4)
4 (0.2)
3 (0.2)
8 (0.4)
1.14 (0.41-3.15)
0.54 (0.21-1.35)
0.75 (0.26-2.16)
0.20 (0.02-1.71)
0.67 (0.11-3.99)
0.67 (0.11-3.99)
0.57 (0.17-1.95)
0.50 (0.09-2.73)
0.67 (0.11-3.99)
1.00 (0.38-2.66)
0.798
0.185
0.591
0.141
0.656
0.656
0.371
0.423
0.656
0.999
6 (0.3)
9 (0.5)
3 (0.2)
3 (0.2)
8 (0.4)
1 (0.1)
1 (0.1)
1 (0.1)
9 (0.5)
12 (0.6)
4 (0.2)
7 (0.4)
11 (0.6)
6 (0.3)
5 (0.3)
5 (0.3)
0.82 (0.34-1.97)
2.00 (0.75-5.34)
0.80 (0.22-2.98)
1.40 (0.44-4.41)
0.654
0.165
0.739
0.567
*Primary endpoint
: a composite of cardiac death, nonfatal MI, stent thrombosis, stroke and PLATO major bleeding at 1 month
Secondary Endpoints at 1 Month
Cardiac Death
Nonfatal MI
Periprocedural MI
Spontaneous MI
p=0.798
p=0.185
p=0.591
p=0.141
0.69%
0.43%
0.37%
0.32%
0.27%
0.43%
0.37%
0.05%
TAT
DDAT
TAT
DDAT
TAT
DDAT
TAT
DDAT
N=1,879
N=1,876
N=1,879
N=1,876
N=1,879
N=1,876
N=1,879
N=1,876
Secondary Endpoints at 1 Month
ARC Stent Thrombosis
Definite/Probable ST
Definite ST
Probable ST
p=0.371
p=0.423
p=0.656
0.37%
0.21%
0.21%
0.16%
0.11%
0.11%
TAT
DDAT
TAT
DDAT
TAT
DDAT
N=1,879
N=1,876
N=1,879
N=1,876
N=1,879
N=1,876
Secondary Endpoints at 1 Month
Stroke
PLATO
Major Bleeding
p=0.656
p=0.999
0.43%
0.43%
0.16%
0.11%
TAT
DDAT
TAT
DDAT
N=1,879
N=1,876
N=1,879
N=1,876
Other Events at 1 Month
All-Cause Death
PLATO
Minor Bleeding
Target Lesion
Revascularization
Target Vessel
Revascularization
p=0.654
p=0.165
p=0.739
p=0.567
0.64%
0.37%
0.32%
0.59%
0.27%
0.48%
0.27%
0.21%
TAT
DDAT
TAT
DDAT
TAT
DDAT
TAT
DDAT
N=1,879
N=1,876
N=1,879
N=1,876
N=1,879
N=1,876
N=1,879
N=1,876
Per-Protocol Analysis
TAT
DDAT
(N=1,773)
(N=1,637)
Hazard Ratio
(95% CI)
P
21 (1.2)
27 (1.6)
0.73 (0.42-1.30)
0.287
Cardiac death
7 (0.4)
7 (0.4)
0.92 (0.33-2.70)
0.918
Nonfatal MI
6 (0.3)
13 (0.8)
0.44 (0.17-1.15)
0.092
Periprocedural MI
6 (0.3)
8 (0.5)
0.71 (0.25-2.04)
0.522
Spontaneous MI
0 (0.0)
5 (0.3)
-
0.021
1 (0.1)
3 (0.2)
0.32 (0.03-3.03)
0.317
Ischemic stroke
1 (0.1)
3 (0.2)
0.32 (0.03-3.03)
0.317
ST, definite or probable
3 (0.2)
7 (0.4)
0.41 (0.11-1.57)
0.191
ST, definite
1 (0.1)
4 (0.2)
0.24 (0.03-2.12)
0.198
ST, probable
2 (0.1)
3 (0.2)
0.63 (0.11-3.78)
0.614
8 (0.5)
8 (0.5)
0.95 (0.36-2.52)
0.912
End point
Primary end point
Secondary end points
Stroke
PLATO major bleeding
*Primary endpoint
: a composite of cardiac death, nonfatal MI, stent thrombosis, stroke and PLATO major bleeding at 1 month
Primary Endpoint – Per Protocol
Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
Cumulative Incidence of
Primary Endpoint (%)
4
HR: 0.73 (0.42-1.30)
P=0.287
3
2
DDAT: 1.6%
1
TAT: 1.2%
0
0
7
14
21
28
35
Days after Randomization
No. at Risk
TAT
1,733
1,714
1,708
1,697
1,637
1,427
DDAT
1,637
1,618
1,607
1,598
1,548
1,337
Subgroup Analysis
Subgroups
Age
Sex
Acute coronary syndrome
Diabetes mellitus
Presence of renal dysfunction
Concomittant use of statin
Concomittant use of CCBs
Allocated stent arm
Multivessel stenting
Total
Δ Absolute Risk at 1 Month
(95% CI)
Pt No.
≥ 65 years
< 65 years
Men
Women
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Promus-Element
Endeavor-Resolute
Yes
No
1,797
1,958
2,568
1,187
2,460
1,295
1,186
2,569
92
3,663
3,196
559
764
2,991
2,503
1,252
2,022
1,733
3,755
-4.0
-3.0
-2.0
-1.0
Favors TAT
0.0
1.0
P
Int P
0.722
0.717
0.295
0.675
0.907
0.393
0.834
0.390
0.663
0.645
0.768
0.410
0.890
0.558
0.725
0.615
0.466
0.966
0.566
0.933
1.5
Favors DDAT
0.319
0.513
0.506
0.756
0.649
0.902
0.829
0.696
On-Clopidogrel Platelet Reactivity
At Baseline
(12-24 hours after the loading dose)
P<0.001
P2Y12 Reaction Units
500
173±97
213±93
TAT
DDAT
400
300
200
100
0
On-Clopidogrel Platelet Reactivity
At 1 Month
(after maintenance dose)
P<0.001
P2Y12 Reaction Units
500
169±80
192±80
TAT
DDAT
400
300
200
100
0
Limitations
1. Event rates were lower than expected
- Expected rate of primary endpoint in DDAT group: 3.0%
- Actual event rate: 1.4%
 Possibility of being underpowered
2. Chance of under-reporting
- Dedicated periodic on-site monitoring was performed
- Event rates after PCI are known to be lower in Asian population
3. Low rates of peri-procedural MI
- Cardiac enzyme measurement was not mandated
4. Non-adherence to allocated treatment may have affected outcomes
- Non-adherence rate: 91.6% (TAT group) and 86.5% (DDAT group)
- However, PP analysis yielded consistent results
Conclusions
• The adjunctive use of cilostazol in addition to
conventional dual antiplatelet therapy was
noninferior to doubling the maintenance dose of
clopidogrel in this all-comer PCI population
receiving exclusively drug-eluting stents with regard
to net clinical outcome at 1 month.
• There were no differences between the two
treatment regimens regarding the individual
components of the primary outcome.
Adjunctive Cilostazol Versus Double Dose
Clopidogrel After PCI with Drug Eluting Stent
: The HOST-ASSURE Randomized Trial
Hyo-Soo Kim, MD/PhD
Kyung-Woo Park, Si-Hyuck Kang, Kwang-Soo Cha,
Byoung-Eun Park, Jay-Young Rhew, Hui-Kyung Jeon, In-Ho Chae
On Behalf of The HOST-ASSURE Trial Investigators
Seoul National University Hospital, Seoul, Korea