Adjunctive Cilostazol Versus Double Dose Clopidogrel...
Transcript of Adjunctive Cilostazol Versus Double Dose Clopidogrel...
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
Case 66/M
NSTEMI, Killip class III
Left main coronary artery disease
Case
Do you think DAT is enough?
Aspirin 100 mg Clopidogrel 75 mg
Case 4 days after successful PCI with TaxusTM
: Subacute stent thrombosis
DAT was not enough to protect this patient.
Then, what is your choice?
Aspirin 100 mg Clopidogrel 75 mg
What is your choice?
+ +
Double-Dose Clopidogrel
Dual Antiplatelet Therapy
Triple Antiplatelet Therapy
(aspirin + clopidogrel + cilostazol)
TAT DDAT vs.
cilostazol
This is theme of HOST-ASSURE-RCT.
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
Double-Dose
Clopidogrel Dual
Antiplatelet Therapy
(DDAT)
Triple Antiplatelet
Therapy
(TAT) vs.
2x2 Factorial Design
PtCr-EES
(PromusTM
ElementTM)
CoCr-ZES
(Endeavor® -
Resolute) vs.
Platelet arm
Stent arm
Objectives
Double-Dose
Clopidogrel Dual
Antiplatelet Therapy
(DDAT)
Triple Antiplatelet
Therapy
(TAT) vs.
2x2 Factorial Design
[Hypothesis]
TAT is non-inferior to DDAT
regarding net clinical outcome at 1 month
vs. Triple Antiplatelet
Therapy
(TAT)
Double-Dose
Clopidogrel Dual
Antiplatelet Therapy
(DDAT)
Study Design
TAT arm (N=1,875)
DDAT arm (N=1,875)
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
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 Arm
2:1 Randomization
Anti-Platelet Arm
1:1 Randomization
40 Centers in Korea
2x2
Fa
cto
ria
l 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 ischemia
or 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
• GI or GU bleeding ≤ 3 months
or major surgery ≤ 2 months
• Life expectancy <1 year
• Actively participating in another drug or
device investigational study
• LVEF <25% or cardiogenic shock
• 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 Assay
1) 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
Web-based online randomization system
Dream CIS Inc. (contract research organization)
Seung-Woo Park, Young-Jin Choi, Kwangil Kim
Yong-Seok Kim, Sang Min Park, Nae Hee Lee
(blinded to treatment allocation)
Trial Coordination
Randomization
Data Safety
Monitoring Board
Data Management
Clinical Event
Adjudication
Committee
Principal
Investigator
Hyo-Soo Kim, In-Ho Chae, Kwang Soo Cha,
Byoung Eun Park, Jay Young Rhew, Hui-Kyung Jeon
Executive
Committee
Participating Centers 40 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 Patients
Enrolled 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 Analyzed
According to ITT
1,876 Patients Analyzed
According 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 0.639
Stent 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 0.513
Use of IVUS or OCT 737 (39.2) 763 (40.7) 0.365
Treatment of left main disease 57 (3.0) 55 (2.9) 0.852
Treatment of bifurcation lesions 308 (16.4) 303 (16.2) 0.842
Use 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
lati
ve I
ncid
en
ce o
f
Pri
mary
En
dp
oin
t (%
)
0 7 14 21 28 35
0
1
2
3
4
TAT: 1.2%
DDAT: 1.4%
Primary Endpoint
No. at Risk
Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
Days after Randomization
Non-inferiority P<0.001
Superiority 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
mu
lati
ve I
ncid
en
ce o
f
Pri
mary
En
dp
oin
t (%
)
0 7 14 21 28 35
Days after Randomization
0.0
0.5
1.0
1.5
P=0.343
P=0.566 Overall P=0.565
Composite of Cardiac death, nonfatal MI, stroke,
definite/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 Endpoint Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
-0.5 0.5 1.0 0.0
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
In
cid
en
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
In
cid
en
ce
(%
) Overall P=0.999
0.0
0.5
1.0
1.5
P=0.999 P=0.999
PLATO Major Bleeding
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
In
cid
en
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
lati
ve
In
cid
en
ce
(%
) 0 7 14 21 28 35
Days after Randomization
0.0
0.5
1.0
1.5
P=0.343
P=0.566
Overall P=0.565
Primary Endpoint
DDAT
TAT
Cu
mu
lati
ve
In
cid
en
ce
(%
)
0 7 14 21 28 35
Days after Randomization
Overall P=0.654
0.0
0.5
1.0
1.5
P=0.157 P=0.659
Stroke
DDAT
TAT
Cu
mu
lati
ve
In
cid
en
ce
(%
)
Clinical Outcomes
End point
Event Rates at D/C 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)
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
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=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%
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=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
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=1,876
Stroke
p=0.656
PLATO
Major Bleeding
p=0.999
0.11% 0.16%
0.43% 0.43%
Other Events at 1 Month
All-Cause Death
p=0.654
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=1,876
TAT N=1,879
DDAT N=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
lati
ve I
ncid
en
ce o
f
Pri
mary
En
dp
oin
t (%
)
0 7 14 21 28 35
0
1
2
3
4
TAT: 1.2%
DDAT: 1.6%
No. at Risk Days after Randomization
Primary Endpoint – Per Protocol Composite of Cardiac death, nonfatal MI, stroke,
definite/probable ST, and PLATO major bleeding
HR: 0.73 (0.42-1.30)
P=0.287
Subgroup Analysis
Subgroups Pt 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 0.319
Women 1,187 0.675
Acute coronary syndrome Yes 2,460 0.907 0.513
No 1,295 0.393
Diabetes mellitus Yes 1,186 0.834 0.506
No 2,569 0.390
renal dysfunction Yes 92 0.663 0.756
No 3,663 0.645
Concomittant use of statin Yes 3,196 0.768 0.649
No 559 0.410
Concomittant use of CCBs Yes 764 0.890 0.902
No 2,991 0.558
Allocated stent arm Promus-Element 2,503 0.725 0.829
Endeavor-Resolute 1,252 0.615
Multivessel stenting Yes 2,022 0.466 0.696
No 1,733 0.966
Total 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<0.001
P2Y
12 R
eacti
on
Un
its
At 1 Month (after maintenance dose)
0
100
200
300
400
500
TAT DDAT
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%
- Based on previous study (3.7% at 1 mo in CURRENT study)
- Actual event rate: 1.4% (ITT) & 1.6% (PP)
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 unless significant sx or sign
- The clinically-significant events are all counted
4. Non-adherence to allocated treatment may have affected outcomes
- Adherence rate: 91.6% (TAT group) and 86.5% (DDAT group)
- However, PP analysis yielded consistent results with ITT
• 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.
• Both potent antiplatelet regimens for 1 month were safe,
effective, and widely applliable to the daily practice to
improve clinical outcome after DES implantation.
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