Curr Cardiol Rep (2014) 16:485
DOI 10.1007/s11886-014-0485-4
GLOBAL CARDIOVASCULAR HEALTH (SC SMITH, SECTION EDITOR)
“East Asian Paradox”: Challenge for the Current Antiplatelet
Strategy of “One-Guideline-Fits-All Races” in Acute Coronary
Syndrome
Young-Hoon Jeong
Published online: 27 March 2014
# Springer Science+Business Media New York 2014
Abstract Clinical experiences have suggested that East
Asians show the higher risk of warfarin-related intracranial
hemorrhage compared with Westerners. Therefore, different
target of the International Normalized Ratio (INR) in East
Asians (1.6–2.6) has been proposed and adapted in clinical
practice. In terms with antiplatelet therapy, recent evidence
has supported the concept of “therapeutic level of platelet
reactivity” to balance clinical efficacy and safety in patients
undergoing percutaneous coronary intervention (PCI) or those
with acute coronary syndrome (ACS). In line with the warfa-
rin experiences, multiple clinical and pharmacodynamic data
from East Asians have shown their different therapeutic level
of platelet reactivity following PCI or ACS (“East Asian
Paradox”). Furthermore, like most cardiovascular drugs,
P2Y12 receptor blockers have marked interethnic differences
in the pharmacokinetics and pharmacodynamics. The currently
performed clinical trials evaluating the clinical efficacy and
safety of potent P2Y12 inhibitors mostly don’t include enough
number of East Asians to draw reliable conclusions. Therefore,
dedicated research and guideline(s) for East Asians are required
before we can apply Western recommendations for potent
P2Y12 inhibitors in East Asian population. It is a time to
consider the paradigm shift from “one-guideline-fits-all races”
to “race-tailored antiplatelet therapy” in treating ACS patients.
Keywords Race . Warfarin . P2Y12 inhibitor . Acute coronary
syndrome . Thrombogenicity . East Asian Paradox .
Antiplatelet strategy
This article is part of the Topical Collection on Global Cardiovascular
Health
Y.<H. Jeong (*)
Division of Cardiology, Department of Internal Medicine,
Gyeongsang National University Hospital and Gyeongsang National
University School of Medicine, 79 Gangnam-ro, Jinju,
Gyeongsangnam-do 660-702, Korea
e-mail: goodoctor@naver.com
Introduction
In a wide spectrum of patients with high-risk coronary artery
disease (CAD), dual antiplatelet therapy (DAPT) with aspirin
and P2Y12 receptor inhibitor has been the mainstay treatment
strategy to prevent ischemic events following percutaneous
coronary intervention (PCI) [1]. Unlike aspirin, multiple lines
of evidence have demonstrated that clopidogrel therapy is
associated with wide interindividual variability in pharmaco-
dynamic response [2•]. Patients who are poor responders or
who have high on-clopidogrel platelet reactivity (HPR) to
adenosine diphosphate (ADP) are at increased risk of post-
PCI ischemic event occurrence. The linkage of HPR to ische-
mic events may be different according to the disease activity,
which appears distinct in patients with acute coronary syn-
drome (ACS) but not in patients with stable CAD [3, 4]. In
addition, the recent data suggest that low on-treatment platelet
reactivity (LPR) to ADP is associated with a higher risk of
bleeding [2•]. Therefore, a therapeutic window concept has
been proposed for P2Y12 inhibitor therapy. Several issues
have been suggested and debated in the decision of therapeu-
tic level of platelet reactivity in PCI-treated patients. This
article will review the available evidence addressing the
unique relation of platelet reactivity to thrombotic and bleed-
ing events in the East Asians. The concept of “East Asian
Paradox” needs to be tested in future investigations of person-
alized antiplatelet therapy in the era of potent P2Y12 inhibitor.
Ample Evidence of “East Asian Paradox”
The clinical experience with warfarin has raised the concern that
Asians might experience a substantially higher risk of intracra-
nial hemorrhage compared with Western individuals, even hav-
ing the similar range of the International Normalized Ratio
(INR) [5, 6]. Guidelines regarding target INR are mainly derived
485, Page 2 of 8
from clinical trials performed in Western populations, but have
been adopted for the management of anticoagulation therapy in
all ethnic groups. However, some investigators have suggested
that an individualized target INR depending on the races may be
different, and an INR value of 1.6–2.6 would be more adequate
in Asians [7, 8]. Although there is no conclusive evidence to
explain more bleeding tendency during warfarin therapy in
Asians, differences in the drug metabolism, genetic variants
and hypercoagulability factors may be potential explanations.
Likewise, the optimal regimen and dosage of P2Y12 plate-
let receptor inhibitor might be different across the races.
Multiple pharmacodynamic and clinical evidences have eval-
uated the important variables on clopidogrel response, which
mostly demonstrated that the cytochrome P450 (CYP) 2C19
loss-of-function (LoF) allele is the main determinant in terms
with the level of platelet reactivity and the prevalence of HPR
during clopidogrel treatment [9•]. There are multiple
CYP2C19 alleles associated with LoF (*2-*8), and interethnic
differences in LoF carriage exist (Table 1). Approximately
30 % of Caucasians are CYP2C19 LoF allele carriers with
the vast majority carrying the *2 allele. However, about 60 %
of East Asians carry CYP2C19 LoF allele; ~50 % carry the *2
allele, and the rest carry the *3 allele. Furthermore, the influ-
ence of the CYP2C19*3 allele on the antiplatelet response to
clopidogrel seems greater compared with the CYP2C19*2
allele [10]. It has been suggested that the high prevalence of
the CYP2C19 LoF allele carriage in East Asians may explain
the higher prevalence of HPR during clopidogrel treatment.
Although Korean patients treated with elective PCI were loaded
with high-dose clopidogrel of 600 mg, the prevalence of HPR
(using Western HPR criteria) measured by various platelet
function tests appeared greater compared with Westerners
(40.1–63.5 % vs 20 to 35 %) [2•, 11]. Furthermore, clinical
studies performed in East Asians have reported the higher
cutoffs of HPR (using receiver-operating characteristic [ROC]
curve analysis) than those of the Western population (252.5–
289 vs 208–240 P2Y12 reaction units [PRU] by the VerifyNow
P2Y12 assay) [2•, 3, 12–17] (Table 2).
Table 1 Frequency of CYP2C19*2 and *3 minor alleles and genetically
predicted phenotype across the races
*2 allele *3 allele % intermediate % poor
frequency frequency metabolizer metabolizer
European 0.14 0.0 24 2 Koreans receiving DAPT with aspirin and clopidogrel [25].
Asian 0.27 0.09 46 10
African 0.14 0.0 24 2 (Bleeding Academic Research Consortium) bleeding events
African American 0.18 0.008 30 3.5
Estimates based on HapMap and PharGKB data (http://www.pharmgkb.
org) and [9•, 10].
Intermediate and poor metabolizers indicate the carriers of 1 and 2
CYP2C19 loss-of-function allele(s), respectively.
Curr Cardiol Rep (2014) 16:485
Despite the higher level of platelet reactivity in East Asians
vs Westerners during clopidogrel treatment, numerous clinical
data have shown that East Asians may have similar or even
lower rates of post-PCI ischemic event occurrence compared
with Westerners [18]. In the CHARISMA (Clopidogrel for
High Atherothrombotic Risk and Ischemic Stabilization,
Management, and Avoidance) study including approximately
15,000 patients with atherothrombosis (a median follow-up
period of 28 months) [19•], Asian population has a lower rate
of the composite of cardiovascular death, myocardial infarc-
tion, and stroke (Asians vs Blacks vs Whites vs Hispanics:
6.2 % vs 8.6 % vs 7.1 % vs 6.8 %, respectively), and a higher
propensity for moderate GUSTO (Global Utilization of
Streptokinase and Tissue-plasminogen activator for
Occluded coronary arteries) bleeding (Asians vs Blacks vs
Whites vs Hispanics: 2.5 % vs 3.5 % vs 1.7 % vs 1.2 %,
respectively), during antiplatelet therapy compared with other
races. Clinical data from Korean and Japan also have shown a
much lower incidence of stent thrombosis after implantation
of the first-generation drug-eluting stent (DES) (~0.2 %/year)
compared with the data from Western registries (~0.6 %/year)
[20–22]. The recent analysis of the NCDR (National
Cardiovascular Data Registry CathPCI Registry) database
(n=423,965 Americans) also supported the favorable clinical
outcomes in Asians [23•]. Despite the similar trends in adop-
tion of DES, Asian patients undergoing PCI showed the
similar long-term clinical outcomes compared with Whites
(hazard ratio [HR]: 0.99; 95 % confidence interval [CI]:
0.92–1.08) in the era of clopidogrel treatment.
Contrary to the risk of post-PCI ischemic event in East
Asians, the risk of serious bleeding in this race seemed greater
compared with Westerners. Japanese patients treated with
elective DES implantation (n=184) were treated with aspirin
and a thienopyridine (200 mg/day ticlopidine or 75 mg/day
clopidogrel), and 6.5 % of major bleeding was observed
during the 16-month mean duration of DAPT [24]. Major
bleeding occurred more frequently in high-responders (lower
quartile group assessed by platelet aggregation threshold in-
dex) than other groups (15 % vs 4.2 %, P=0.02). High-
responsiveness was the independent predictor of major bleed-
ing (odds ratio: 4.26; 95 % CI: 1.09–16.67; P=0.03). The
ACCEL-BLEED (A Correlation between on-ClopidogrEL
platelet reactivity and Bleeding following percutaneous coro-
nary intervention) study evaluated the relation between plate-
let reactivity and the rate of mild bleeding in PCI-treated
During 1-month follow-up following PCI, 29.3 % of BARC
were observed; 22.3 % of BARC bleeding type 1 and 7.0 % of
BARC bleeding type 2. Lower quartile group of platelet
reactivity at 1-month follow-up (vasodilator-stimulated phos-
phoprotein phosphorylation [VASP-P] index <34.7 %) was
significantly associated with the increased risk of BARC
Curr Cardiol Rep (2014) 16:485 Page 3 of 8, 485

Table 2 ROC curve analysis: HPR Cutoffs of the VerifyNow P2Y12 assay in PCI-treated East Asian Patients (total n=3844)

Study Cohort Follow-up Primary endpoint Cutoff

ACCEL-LOADING-ACS NSTE-ACS (n=218); 1-mo. CV death, nonfatal PRU≥289

study (RCT) [12] emergent PCI MI, and TVR
Zhang et al. (Registry) [13] NSTE-ACS (n=228); 1-mo. CV death, nonfatal MI, stent PRU>272
emergent PCI thrombosis and TVR
Ko et al. (Registry) [14] All comer (n=222); 1-mo. Death, nonfatal MI, stroke, PRU≥275
PCI and TVR
CILON-T study (RCT) [15] All comer (n=960); 6-mo. Cardiac death, nonfatal MI, PRU≥252.5
DES implantation ischemic stroke, and TLR
Ahn et al. (Registry) [3] All comer (n=1226); 12-mo. CV death, nonfatal MI, Non-AMI: no cutoff
stenting and stent thrombosis AMI: PRU≥272
CROSS-VERIFY cohort All comer (n=809); 12-mo. Cardiac death and nonfatal MI PRU≥275
(Registry) [16] elective PCI
Jin et al. (Registry) [17] STEMI (n=181); 12-mo. CV death, nonfatal MI, and PRU≥282
primary PCI ischemic stroke

AMI acute myocardial infarction, ACCEL-LOADING-ACS ACCELerated inhibition of platelet aggregation, inflammation and myonecrosis by
adjunctive cilostazol LOADING in patients with Acute Coronary Syndrome, CILON-T influence of CILostazol-based triple antiplatelet therapy ON
ischemic complication after drug-eluting stenT implantation, CROSS-VERIFY measuring clopidogrel resistance to assure safety after percutaneous
coronary intervention using VerifyNow, CV cardiovascular, HPR high on-treatment platelet reactivity, DES drug-eluting stent, NSTE-ACS Non-ST-
elevation acute coronary syndrome, PCI percutaneous coronary intervention, PRU P2Y12 reaction units, RCT randomized controlled trial, ROC
receiver-operating characteristic, STEMI ST-segment-elevation myocardial infarction, TLR target lesion revascularization, TVR target vessel
revascularization.

bleeding type 2 compared with other groups (1st vs 2nd vs 3rd
vs 4th quartile: 13.3 % vs 5.3 % vs 5.3 % vs 4.0 %; P=0.033).
This cutoff of LPR seemed higher than that observed in
Western population (VASP-P index <17 %) [26].
Like the experience with warfarin, multiple clinical evi-
dence has proposed that the therapeutic level of platelet reac-
tivity (i.e., the levels of HPR and LPR) during P2Y12 receptor
inhibitor in PCI-treated East Asians might be higher compared
with Westerners –“East Asian Paradox”. In addition, the rel-
ative influence of platelet reactivity to ischemic or bleeding
event may differ between East Asians vs Westerners.
Therefore, observed findings suggest that dedicated clinical
studies and guidelines are warranted to indicate optimal anti-
platelet regimen in the East Asian population.
Plausible Explanations for “East Asian Paradox”
Arterial Thrombosis is a Highly Complex Process
After Virchow first suggested over 150 years ago that a triad
of conditions predispose to thrombus formation, this concept
has now expanded into multiple components [27]. Arterial
thrombi have been traditionally considered to be composed
differently than venous thrombi (“white” vs “red” clot).
Arterial thrombosis is platelet-rich and superimposed on rup-
tured and inflamed atherosclerotic lesions. However, stabili-
zation of newly generated thrombus following initial platelet
activation and adhesion after plaque rupture requires adequate
activation of the coagulation system leading to thrombin and
fibrin generation. Experimental studies suggest that arterial
and venous thrombosis are finely regulated processes involv-
ing a highly complex interplay between platelets and other
blood cells, soluble plasma proteins, and the vessel wall (so
called “thrombogenicity” or “hypercoagulability”).
The convincing associations of arterial thrombosis to co-
agulation and inflammation have been repeatedly demonstrat-
ed in clinical trials. A log-linear relation between fibrinogen
level for the risk of any CAD, stroke, and other vascular and
nonvascular mortality was demonstrated in a meta-analysis of
154,211 individuals with no known CAD [28]. The age- and
sex- adjusted hazard ratio per 1 g/L increase in fibrinogen
level for CAD was 2.42 (95 % CI, 2.24–2.60); stroke, 2.06
(95 % CI, 1.83–2.33); other vascular mortality, 2.76 (95 % CI,
2.28–3.35); and nonvascular mortality, 2.03 (95 % CI, 1.90–
2.18). A meta-analysis of 66,155 cases and 91,307 controls
demonstrated that factor V Leiden (G1691A) and prothrom-
bin G20210A gene mutations were associated with an in-
creased risk of CAD and myocardial infarction by 1.17 and
1.31-folds, respectively [29]. The association between plasma
fibrinolysis activation markers and CAD also has been sug-
gested [30]. In addition, another meta-analysis including
160,309 individuals indicated that a 3-fold increase in high-
sensitivity C-reactive protein (CRP) increased the risk of CAD
by 1.23 after adjustment for age, sex, traditional risk factors,
and fibrinogen [31].
The relationships between hypercoagulability factors
(including inflammation, coagulation, and fibrinolysis
markers) and ischemic events also have been identified in
patients with ACS or undergoing PCI. The level of fibrinogen
485, Page 4 of 8
was significantly associated with the risk of peri-procedural
and long-term ischemic events following PCI [32, 33].
Assessment of endogenous thrombolytic status (based on the
lysis time measured by global thrombosis test) predicted the
future ischemic events in ACS patients [34]. Multiple clinical
studies also have shown that elevated CRP levels are signif-
icantly associated with an increased risk of ischemic event
occurrence including stent thrombosis in PCI-treated patients
[12, 34–36]. In this connection, anticoagulant therapy can
reduce the risk of ischemic events in selected CAD patients.
In the ATLAS-ACS 2 TIMI 51 (Anti-Xa therapy to lower
cardiovascular events in addition to standard therapy in pa-
tients with acute coronary syndrome-thrombolysis in myocar-
dial infarction 51) trial, the addition of factor Xa inhibition
with low-dose rivaroxaban to DAPT reduced the risk of stent
thrombosis by 31 % in patients with a recent ACS [37•].
Ethnic Differences in Thrombogenicity
To date, there is no definite evidence to suggest that differences
in intrinsic platelet function exist between the races. However,
there are numerous data suggesting inter-ethnic differences in
thrombogenicity including coagulation, fibrinolysis, and in-
flammation markers. Several population-based clinical trials
have reported different incidences of venous thromboembolism
(VTE) across the races [38, 39•]. African Americans have about
a 30 %–60 % higher incidence of VTE than Caucasians, and an
approximately 2–3 fold increased incidence of VTE compared
with Asian Americans. In most studies, patients of Asian de-
scent appear to have a lower rate of VTE than other races. In
addition, prevalence of arterial thrombosis also has been shown
to increase in the Black race compared with non-Black race
[40]. After multivariate analysis including median income and
clopidogrel compliance, the Black race emerged as a strong
predictor of definite early and late stent thrombosis (HR, 2.07
and 2.60) following DES implantation during clopidogrel treat-
ment. This observation may not only be explained by platelet
function since prevalence of the CYP2C19 LoF alleles appears
similar between the Black and Caucasian races.
Multiple factors may be related with this disparity between
the races. The differences in genetic polymorphisms between
the races may be a piece of underlying mechanism [39•]. For
example, factor V Leiden (G1691A) and prothrombin
G20210A gene mutations are more common in Caucasians
compared with Asians. The differences in the levels of hemo-
static factors (eg, fibrinogen, D-dimer, factor VIII) and plasma
endothelial activation markers (eg, von Willebrand factors,
ICAM-1, E-selectin) may be another contributing factors to
the racial disparity. The MESA (Multi-ethnic Study of
Atherosclerosis) study evaluated these components in individ-
uals living in the USA [41]. African Americans generally had
the most thrombogenic and dysfunctional endothelial profile,
followed by Hispanics and Caucasians with similar levels, and
Curr Cardiol Rep (2014) 16:485
finally East Asians. A growing body of evidence has demon-
strated the close linkage between inflammation and athero-
thrombosis. In addition, multiple studies have suggested the
different levels of inflammatory markers between the races.
East Asians appear to have the lowest level of inflammation
compared with Westerners [42–44]. For example, the
Women’s Health Study demonstrated that African American
women have significantly higher median CRP levels (n=475:
2.96 mg/L) compared with Caucasians (n=24,455: 2.02 mg/
L), Hispanic (n=254: 2.06 mg/L), and Asian counterparts (n=
357: 1.12 mg/L) [44].
Because each component of hypercoagulability factors may
not reflect in vivo global thrombogenicity property, we need to
adopt reliable indicator(s) incorporating these factors together.
Of several interesting experimental tools, the global thrombosis
test can be a favorable candidate to assess thrombotic status and
endogenous thrombolytic activity, in which ‘occlusion time’
reflects shear-induced platelet-fibrin linked thrombi under path-
ophysiological conditions [45••]. Japanese healthy patients
showed longer occlusion time compared with UK Westerners
(545 vs 364 sec, P <0.0001), which may mean the lower level of
thrombogenicity in East Asians vs Westerners.
The clinical manifestation of these hypercoagulability factors
is also variable and finely modulated by gene-environment
interactions. Obesity may be considered an important risk factor
associated with a prothrombotic state. Obesity increases the risk
of arterial or venous thrombosis by 1.5–2.5 fold, and may cause
a hypercoagulable state through several mechanisms [46]: (1)
platelet activation through change of leptin, adiponectin, and
proinflammatory cytokine levels; (2) increased procoagulant
activity and reduced fibrinolytic activity by secretion of tissue
factor, PAI-1, and possibly thrombin-activatable fibrinolysis in-
hibitor (TAFI) by adipose tissue; and (3) increased hepatic
production of coagulation factors and PAI-1 by increased proin-
flammatory cytokines. Compared with East Asians, Western
populations, especially African-American, show a higher preva-
lence of severe obesity, which may increase the propensity for
thrombosis status in this race.
Taken together, East Asians appear to have the lower level
of thrombogenicity compared with Western population. If the
patients have different levels in integrated hypercoagulability,
the relationship between platelet function and clinical ische-
mic event can be different [47, 48]. The latter observation may
explain why the East Asian population has a lower risk of
ischemic event occurrence and a higher propensity for bleed-
ing during clopidogrel treatment after PCI.
Future Direction: Evidences of Potent P2Y12 Inhibitor
in East Asians
There is growing use of more potent P2Y12 receptor inhibitors
than clopidogrel in PCI-treated ACS patients. Like most
Curr Cardiol Rep (2014) 16:485
cardiovascular drugs including clopidogrel [49], marked in-
terethnic differences in the pharmacokinetics and pharmaco-
dynamics of potent P2Y12 receptor blockers also exist. For
example, exposure of the active metabolite during prasugrel
treatment was higher in East Asians including Chinese,
Japanese, and Korean populations (~30 %) compared with
Caucasians even after adjustment for body weight [50•]. In
line with the pharmacokinetic data, 10 mg/d prasugrel therapy
in Caucasians showed similar level of platelet inhibition com-
pared with 5 mg/d prasugrel therapy in East Asians. Likewise,
exposure of the active metabolite (ticagrelor and AR-
C124910XX) during ticagrelor maintenance therapy was also
higher in Chinese compared (~20 %) with Caucasians even
after adjustment for body weight [51, 52]. When considering
higher therapeutic level of platelet reactivity in East Asians,
the optimal dosage of these potent P2Y12 inhibitors (prasugrel
and ticagrelor) in East Asian ACS patients might be different
with Westerners. However, initial prospective clinical trials
(Trial to Assess Improvement in Therapeutic Outcomes by
Optimizing Platelet Inhibition With Prasugrel-TIMI 38
[TRITON-TIMI 38] and PLATelet Inhibition and Patient
Outcomes [PLATO]) evaluating the clinical efficacy and safe-
ty of potent P2Y12 inhibitors in ACS patients [53, 54] enrolled
a very limited number of Asians. Therefore, it is difficult to
draw reliable conclusions regarding whether these potent
P2Y12 receptor inhibitors will provide similar benefits in
East Asians compared with other races.
In this point, the TRILOGY-ACS (Targeted Platelet
Inhibition to Clarify the Optimal Strategy to Medically
Manage Acute Coronary Syndromes) study suggested the
interesting result for East Asians [55]. This study enrolled
752 East Asians under the age of 75 years (8.1 % of the total
cohort) and compared the clinical outcomes during 10 mg/d
prasugrel vs 75 mg/d clopidogrel therapy on top of aspirin.
Contrary to overall results in terms with the primary endpoint
of cardiovascular death, myocardial infarction or stroke (HR
in the prasugrel group: 0.91; 95 % CI: 0.79–1.05; P=0.21),
East Asians showed the opposite trend (HR in the prasugrel
group: 1.19; 95 % CI: 0.75–1.89). In addition, the “real world”
clinical data from Western population have shown that LPR
during prasugrel therapy (~30 % of total cohort) substantially
increased the risk of serious bleeding in ACS patients during
1-year follow-up (15.5 % of TIMI minor or major bleeding)
[56]. In the era of potent P2Y12 receptor inhibitors, the con-
cept of LPR and overcoming the risk of bleeding may be the
emerging target to balance the efficacy and safety of these
drugs.
Although there have been no conclusive large-scale clinical
trials including East Asians only, recent pharmacodynamic
and clinical studies have suggested more insight and confi-
dence for the “East Asian Paradox”. In stented Koreans,
10 mg/d prasugrel achieved the lowest level of PRU compared
with 5 mg/d prasugrel and 75 mg/d clopidogrel (80±46 vs163±
Page 5 of 8, 485
61 vs 214±69 PRUs, P<0.001) [57] (Fig. 1). In terms of
speculated therapeutic level of platelet reactivity (130–275
PRUs) from previous East Asian data [3, 12–17, 25], 75 mg/d
clopidogrel appeared weaker and most of the patients receiving
10 mg/d prasugrel (up to 90 %) met the criteria of LPR. The
results of recent randomized clinical trials also supported the
findings of pharmacodynamic study. The PRASFIT-ACS
(PRASugrel compared to Clopidogrel For Japanese PatIenTs
with ACS undergoing PCI) study including PCI-treated
Japanese patients with ACS (n=1363) showed a favorable trend
for low-dose prasugrel (20 mg loading, followed by daily
3.75 mg) compared with standard-dose clopidogrel (300 mg
loading, followed by daily 75 mg) in the primary composite
endpoint of cardiovascular death, myocardial infarction, or is-
chemic stroke (9.4 % vs 11.8 %; HR: 0.77; 95 % CI: 0.56–1.07;
P=0.12), with no difference in TIMI major bleeding (1.9 % vs
2.2 %; HR: 0.82; P=0.38) [58••]. Meanwhile, the PHILO (the
efficacy and safety of ticagrelor vs clopidogrel in Asian/
Japanese patients with non-ST or ST-elevation ACS for whom
PCI is planned) study including East Asian patients with ACS
undergoing PCI (n=801) evaluated the clinical efficacy and
safety of Western guideline-recommended ticagrelor dose
(180 mg loading, followed by 90 mg twice a day) vs clopidogrel
(300 mg loading, followed by daily 75 mg) [59••]; Numerically,
more primary composite endpoint events were observed with
ticagrelor compared with clopidogrel (10.3 %/year vs 8.5 %/
year; HR: 1.44; 95 % CI: 0.85–2.43), with more increased
Fig. 1 Relation between “Speculated Therapeutic Level of Platelet Re-
activity in East Asians” (green column) and Pharmacodynamic Data of
Different Antiplatelet Regimens. With permission from: Jin HY, Yang
TH. Randomized comparisons of the platelet inhibitory effect of
clopidogrel and two doses of prasugrel in patients receiving antiplatelet
therapy after coronary stent implantation. Daejeon, Korea: Korean Soci-
ety of Cardiology: 2012. [57]
485, Page 6 of 8
tendency for major bleeding (HR: 1.54; 95 % CI: 0.83–2.38).
These studies provide more credence to the “East Asian
Paradox”, and, therefore, large-scale clinical trials are mandato-
ry to identify the optimal antiplatelet regimen and therapeutic
level of platelet reactivity to make satisfying clinical efficacy
and safety in East Asians.
Conclusions
Thrombogenicity may be the whole of intrinsic hypercoagu-
lability factors and differ depending on the disease activity and
races. Because the optimal dosage of antithrombotic regimens
is targeting the therapeutic level to maximally balance clinical
efficacy and safety, we may not apply clinical guidelines
mostly derived from the Western population across all races.
In East Asians, excessive inhibition of platelet function by
potent P2Y12 receptor inhibitors may markedly increase the
risk of serious bleeding without protection against post-PCI
ischemic event occurrence. Therefore, dedicated research and
guideline(s) for East Asians are required before we can apply
Western recommendations for novel antithrombotic therapy in
the former population.
Acknowledgments This study was partly supported by grants from
Institute of the Health Sciences, Gyeongsang National University.
Compliance with Ethics Guidelines
Conflict of Interest Young-Hoon Jeong has received honoraria for
lectures from Sanofi-Aventis, Daiichi Sankyo/Lilly, AstraZeneca,
Haemonetics, and Otsuka; and research grants or support from Han-mi
Pharmaceuticals, Boehringer-Ingelheim, Otsuka, Accumetrics, and
Haemonetics.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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