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 crit-

ical in preventing thrombotic events.

• One-week duration of doubling the dose of clopidogrel was

shown to improve outcome at one month compared with con-

ventional dose in ACS patients undergoing PCI.

• Yet in Asia, the adjunctive use of cilostazol to dual an-

tiplatelet 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 com-

parison of TAT with DDAT to date with regard to clinical out-

come.

Objectives

Double-Dose Clopi-dogrel Dual An-

tiplatelet Therapy(DDAT)

Triple Antiplatelet Therapy

(TAT)vs.

2x2 Factorial Design

PtCr-EES (PromusTM Ele-

mentTM)

CoCr-ZES(Endeavor®-Reso-

lute)vs.

Objectives

Double-Dose Clopi-dogrel Dual An-

tiplatelet Therapy(DDAT)

Triple Antiplatelet Therapy

(TAT)vs.

2x2 Factorial Design

[Hypothesis]

TAT is non-inferior to DDATregarding net clinical outcome at 1 month

vs.Triple Antiplatelet

Therapy(TAT)

Double-Dose Clopi-dogrel Dual An-

tiplatelet Therapy(DDAT)

Study Design

TAT arm(N=1,875)

DDAT arm(N=1,875)

200 mg Cilostazol Loading No Cilostazol Loading

Aspirin 100 mg QDClopidogrel 75 mg QDCilostazol 100mg BID

Aspirin 100 mg QDClopidogrel 150 mg QD

3,750 All Comers Receiving PCI

PtCr-EES arm(N=2,500)

CoCr-ZES arm(N=1,250)

Percutaneous Coronary Intervention

Aspirin 300 mg + Clopidogrel 300-600 mg Loading

Net Clinical Outcome at 1 Month Post-PCI (Intention-To-Treat Analysis)

Stent Arm2:1 Randomization

Anti-Platelet Arm1:1 Randomization

40 Centers in Korea

2x2

Fa

ctor

ial D

esig

n

Prospective, single-blinded, randomized multi-center trial

Enrollment Criteria

General Inclusion Criteria

Angiographic 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 ischemiaor diameter stenosis > 70%

• 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

• 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

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 Assay1) At 12-24 hours after loading of clopidogrel

2) At 1-month F/U under maintenance dose

Statistical Assumption

• 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

Non-inferiority Design for Primary Endpoint

(net clinical outcome at 1 month)

Hyo-Soo Kim

Investigators at the Cardiovascular Clinical Research Centerat Seoul National University Hospital

Dream CIS Inc. (contract research organization)

Seung-Woo Park, Young-Jin Choi, Kwangil Kim

Yong-Seok Kim, Sang Min Park, Nae Hee Lee

Trial Coordination

Trial Coordination

Data Safety Monitor-ing Board

Data Management

Clinical Event Adju-dication Committee

Principal Investiga-tor

Hyo-Soo Kim, In-Ho Chae, Kwang Soo Cha,Byoung Eun Park, Jay Young Rhew, Hui-Kyung Jeon

Executive Commit-tee

Participating Centers40 Hospitals in Republic of Korea

Site PI

Seoul National University Hospital Kim, Hyo-Soo

Seoul National University Bundang Hospital Chae, In-Ho

Pusan National University Hospital Cha, Kwang Soo

Dankook University Hospital Park, Byoung Eun

Presbyterian Medical Center Rhew, Jay Young

Uijeongbu St. Mary’s Hospital Jeon, Hui-Kyung

Ulsan University Hospital Shin, Eun Seok

Samsung Changwon Hospital Oh, Ju Hyeon

Chonnam National University Hospital Jeong, Myung-Ho

Chungbuk National University Hospital Hwang, Kyung-Kuk

Wonju Christian Hospital Yoon, Jung-Han

Inje University Ilsan Paik Hospital Lee, Sung Yun

Boramae Medical Center Kim, Sanghyun

Dong-A Medical Center Park, Tae-Ho

Gangnam Severance Hospital Kwon, Hyuck-Moon

St. Vincent’s Hospital Moon, Keon Woong

Daegu Catholic University Medical Center Ryu, Jae-Kean

Keimyung University Dongsan Medical Center Hur, Seung-Ho

Daegu Fatima Hospital Lee, Bong-Ryul

Gyeongsang National University Hospital Park, Yong-Whi

Site PI

Konyang University Hospital Bae, Jang-Ho

Hallym University Kangdong Sacred Heart Hospital Han, Kyoo-Rok

Ewha Womans University Mokdong Hospital Park, Si-Hoon

Korea University Guro Hospital Rha, Seung-Woon

Hallym University Sacred heart Hospital Park, Woo-Jung

Wongwang University Hospital Oh, Seok-Kyu

Korea University Anam Hospital Lim, Do-Sun

Kwangju Christian Hospital Lee, Seung-Wook

Hallym University Chuncheon Sacred Heart Hospital Yoon, Duck-Hyoung

Kyung Hee University Hospital at Gangdong Kim, Chong-Jin

Seoul Medical Center Kim, Seok-Yeon

Gachon University Gil Hospital Ahn, Taehoon

Samsung Medical Center Gwon, Hyeon-Cheol

Hallym University Kangnam Sacred Heart Hospital Lee, Namho

National Health Insurance Medical Center Jeon, Dong-Woon

Soonchunhyang University Hospital Hyun, Min-Soo

Daejun Eulji University Hospital Lee, Sang

Hanyang University Guri Hospital Lee, Jaewoong

Kangwon National University Hospital Ryu, Dong Ryeol

Kosin University Gospel Hospital Cha, Tae-Joon

3,755 PatientsEnrolled and Randomized

Allocated to TAT(N=1,879)

Allocated to DDAT(N=1,876)

Received TAT as Randomized(N=1,830)

Received DDAT as Randomized(N=1,730)

Adhered to TAT for 1 Month(N=1,721)

Adhered to DDAT for 1 Month(N=1,623)

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

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

1,879 Patients AnalyzedAccording to ITT

1,876 Patients AnalyzedAccording to ITT

49 Did not receive allocated treatment 4 Did not receive coronary stenting 4 Did not meet inclusion criteria 14 Patient decision 27 Other reasons

146 Did not receive allocated treatment 7 Did not receive coronary stenting 11 Did not meet inclusion criteria 97 Patient decision 31 Other reasons

Trial Flow

Baseline Characteristics

Characteristic TAT(N=1,879)

DDAT(N=1,876)

Age 62.8±10.7 63.7±10.9

Men 1,311 (69.8) 1,257 (67.0)

Body mass index 24.7±3.2 24.6±3.1

Hypertension 1,256 (66.8) 1,286 (68.6)

Diabetes 598 (31.8) 588 (31.3)

insulin-requiring diabetes 66 (3.5) 71 (3.8)

Dyslipidemia 1,206 (64.2) 1,176 (62.7)

Current smoker 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)

Baseline Characteristics

Characteristic TAT(N=1,879)

DDAT(N=1,876)

Clinical diagnosis

Slient ischemia 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)

Baseline laboratory findings

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

Baseline Characteristics

Characteristic TAT(N=1,879)

DDAT(N=1,876)

Medications at discharge

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)

Calcium channel blocker 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)

*CYP3A4-metabolized statin: simvastatin, lovastatin, atorvastatin, etc**Non-CYP3A4-metabolized statin: rosuvastatin, pravastatin, pitavastatin, fluvastatin

Angiographic & Procedural Characteristics

Characteristic TAT(N=1,879)

DDAT(N=1,876)

P Value

Angiographic disease extent 0.631 1-vessel disease 856 (45.6) 877 (46.7) 2-vessel disease 618 (32.9) 590 (31.4) 3-vessel disease 405 (21.6) 409 (21.8)Number of lesions treated per patient 1.5±0.8 1.5±0.8 0.639Stent arm – intention-to-treat 0.972 Promus-Element arm 1,253 (66.7) 1,250 (66.6) Endeavor-Resolute arm 626 (33.3) 626 (33.4)Type of drug-eluting stents – per protocol 0.552

No stents used 14 (0.7) 9 (0.5) Promus-Element 1,198 (63.8) 1,202 (64.1)

Endeavor-Resolute 587 (31.2) 573 (30.5) Others 80 (4.3) 92 (4.9)

Number of stents per patient 1.6±0.9 1.6±0.9 0.513Use of IVUS or OCT 737 (39.2) 763 (40.7) 0.365Treatment of left main disease 57 (3.0) 55 (2.9) 0.852Treatment of bifurcation lesions 308 (16.4) 303 (16.2) 0.842Use of glycoprotein IIb/IIIa inhibitors 46 (2.4) 50 (2.7) 0.673

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

Cu

mu

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rim

ary

En

dp

oin

t (%

)

0 7 14 21 28 350

1

2

3

4

TAT: 1.2%

DDAT: 1.4%

Primary Endpoint

No. at Risk

Composite of Cardiac death, nonfatal MI, stroke, def-inite/probable ST, and PLATO major bleeding

Days after Randomization

Non-inferiority P<0.001Superiority P=0.566

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

No. at Risk

Cu

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En

dp

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)

0 7 14 21 28 35

Days after Randomization

0.0

0.5

1.0

1.5

P=0.343

P=0.566Overall P=0.565

Composite of Cardiac death, nonfatal MI, stroke, def-inite/probable ST, and PLATO major bleeding

TAT

DDAT

TAT(N=1,879)

23 (1.22%)

DDAT(N=1,876)

27 (1.44%)

Absolute Risk Difference: -0.22%(standard error: 0.37%)

Upper 1-sided 97.5% CI: 0.52%

Primary EndpointComposite of Cardiac death, nonfatal MI, stroke, def-inite/probable ST, and PLATO major bleeding

-0.5 0.5 1.00.0

Predefined margin: 0.75%

Non-inferiority P=0.005

Risk Difference with 1-sided 97.5% CI(TAT-DDAT)

Landmark Analysis

0 7 14 21 28 35

Days after Randomization

Cu

mu

lati

ve I

nci

den

ce (

%) Overall P=0.178

0.0

0.5

1.0

1.5

P=0.563

P=0.179

Nonfatal MI

DDAT

TAT

0 7 14 21 28 35

Days after Randomization

Cu

mu

lati

ve I

nci

den

ce (

%) Overall P=0.999

0.0

0.5

1.0

1.5

P=0.999P=0.999

PLATO Major Bleed-ing

DDAT

TAT

0 7 14 21 28 35

Days after Randomization

Overall P=0.797

0.0

0.5

1.0

1.5

P=0.998

P=0.801

Cardiac Death

DDAT

TAT

Cu

mu

lati

ve I

nci

den

ce (

%)

0 7 14 21 28 35

Days after Randomization

Overall P=0.365

0.0

0.5

1.0

1.5

P=0.256

P=0.391

Definite/Probable ST

DDAT

TAT

Cu

mu

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den

ce (

%)

0 7 14 21 28 35

Days after Randomization

0.0

0.5

1.0

1.5

P=0.343

P=0.566Overall P=0.565

Primary Endpoint

DDAT

TATCu

mu

lati

ve I

nci

den

ce (

%)

0 7 14 21 28 35

Days after Randomization

Overall P=0.654

0.0

0.5

1.0

1.5

P=0.157P=0.659

Stroke

DDAT

TAT

Cu

mu

lati

ve I

nci

den

ce (

%)

Clinical Outcomes

End point

Event Rates at D/C Event Rates at 1 MonthHazard Ratio

(95% CI)PTAT

(N=1,879)DDAT

(N=1,876)TAT

(N=1,879)DDAT

(N=1,876)

Primary end point 16 (0.9) 17 (0.9) 23 (1.2) 27 (1.4) 0.85 (0.49-1.48) 0.566

Secondary end points

Cardiac death 6 (0.3) 5 (0.3) 8 (0.4) 7 (0.4) 1.14 (0.41-3.15) 0.798

Nonfatal MI 6 (0.3) 8 (0.4) 7 (0.4) 13 (0.7) 0.54 (0.21-1.35) 0.185

Periprocedural MI 6 (0.3) 8 (0.4) 6 (0.3) 8 (0.4) 0.75 (0.26-2.16) 0.591

Spontaneous MI 0 (0.0) 0 (0.0) 1 (0.1) 5 (0.3) 0.20 (0.02-1.71) 0.141

Stroke 2 (0.1) 3 (0.2) 2 (0.1) 3 (0.2) 0.67 (0.11-3.99) 0.656

Ischemic stroke 2 (0.1) 3 (0.2) 2 (0.1) 3 (0.2) 0.67 (0.11-3.99) 0.656

ST, definite or probable 2 (0.1) 2 (0.1) 4 (0.2) 7 (0.4) 0.57 (0.17-1.95) 0.371

ST, definite 1 (0.1) 0 (0.0) 2 (0.1) 4 (0.2) 0.50 (0.09-2.73) 0.423

ST, probable 1 (0.1) 2 (0.1) 2 (0.1) 3 (0.2) 0.67 (0.11-3.99) 0.656

PLATO major bleeding 3 (0.2) 4 (0.2) 8 (0.4) 8 (0.4) 1.00 (0.38-2.66) 0.999

Other events

All-cause death 6 (0.3) 8 (0.4) 9 (0.5) 11 (0.6) 0.82 (0.34-1.97) 0.654

PLATO minor bleeding 9 (0.5) 1 (0.1) 12 (0.6) 6 (0.3) 2.00 (0.75-5.34) 0.165

TLR 3 (0.2) 1 (0.1) 4 (0.2) 5 (0.3) 0.80 (0.22-2.98) 0.739

TVR 3 (0.2) 1 (0.1) 7 (0.4) 5 (0.3) 1.40 (0.44-4.41) 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

p=0.798

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

Nonfatal MI

p=0.185

Periprocedural MI

p=0.591

Spontaneous MI

p=0.141

0.43%0.37%

0.37%

0.69%

0.32%

0.43%

0.05%

0.27%

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

Secondary Endpoints at 1 Month

Definite/Probable ST

p=0.371

Definite ST

p=0.423

Probable ST

p=0.656

ARC Stent Thrombosis

0.21%

0.37%

0.11%

0.21%

0.11%0.16%

Secondary Endpoints at 1 Month

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

Stroke

p=0.656

PLATOMajor Bleeding

p=0.999

0.11%0.16%

0.43% 0.43%

Other Events at 1 Month

All-Cause Death

p=0.654

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

TATN=1,879

DDATN=1,876

PLATO Minor Bleeding

p=0.165

Target Lesion Revascularization

p=0.739

Target Vessel Revascularization

p=0.567

0.48%0.59%

0.64%

0.32%

0.21%0.27%

0.37%

0.27%

Per-Protocol Analysis

End point TAT(N=1,773)

DDAT(N=1,637)

Hazard Ratio (95% CI) P

Primary end point 21 (1.2) 27 (1.6) 0.73 (0.42-1.30) 0.287

Secondary end points

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

Stroke 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

PLATO major bleeding 8 (0.5) 8 (0.5) 0.95 (0.36-2.52) 0.912

*Primary endpoint: a composite of cardiac death, nonfatal MI, stent thrombosis, stroke and PLATO major bleeding at 1 month

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

Cu

mu

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den

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ary

En

dp

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t (%

)

0 7 14 21 28 350

1

2

3

4

TAT: 1.2%

DDAT: 1.6%

No. at Risk Days after Randomization

Primary Endpoint – Per ProtocolComposite of Cardiac death, nonfatal MI, stroke, def-inite/probable ST, and PLATO major bleeding

HR: 0.73 (0.42-1.30)P=0.287

Subgroup Analysis

SubgroupsPt

No.Δ Absolute Risk at 1 Month

(95% CI)P Int P

Age ≥ 65 years 1,797 0.722 0.933< 65 years 1,958 0.717

Sex Men 2,568 0.295 0.319Women 1,187 0.675

Acute coronary syndrome Yes 2,460 0.907 0.513No 1,295 0.393

Diabetes mellitus Yes 1,186 0.834 0.506No 2,569 0.390

Presence of renal dysfunc-tion

Yes 92 0.663 0.756

No 3,663 0.645Concomittant use of statin Yes 3,196 0.768 0.649

No 559 0.410Concomittant use of CCBs Yes 764 0.890 0.902

No 2,991 0.558Allocated stent arm Promus-Element 2,503 0.725 0.829

Endeavor-Resolute 1,252 0.615Multivessel stenting Yes 2,022 0.466 0.696

No 1,733 0.966Total 3,755 0.566

Favors TAT Favors DDAT

-4.0 -3.0 -2.0 -1.0 0.0 1.0 1.5

On-Clopidogrel Platelet Reactivity

At Baseline(12-24 hours after the loading dose)

0

100

200

300

400

500

TAT DDAT

173±97 213±93

P<0.001P

2Y12

Rea

ctio

n U

nit

s

On-Clopidogrel Platelet Reactivity

At 1 Month(after maintenance dose)

0

100

200

300

400

500

TAT DDAT

P2Y

12 R

eact

ion

Un

its

169±80 192±80

P<0.001

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

• The adjunctive use of cilostazol in addition to con-

ventional 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 treat-

ment regimens regarding the individual components

of the primary outcome.

Conclusions

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