Antiplatelet resistence - significance and how to deal ?

Antiplatelet Drug-resistance
in Asian Population
Dr.k.nagendra
prasad
ANTIPLATELET RESISTENCE in
ASIAN POPULATION

Topic Outline
 Concept of antiplatelet resistence
 Aspirin resistence , types, mechanism
 Laboratory investigations
 Management
 Clopidogrel resistence , mechanism
 Genetic polymorphisms – importance of testing
 High platelet reactivity testing and its importance in
clinical practice
 Management
 Indian statistics
 Guidelines
 Future directions
ASIAN POPULATION

 Dual antiplatelet therapy combining aspirin
and clopidogrel is the standard care for
patients who have acute coronary syndromes
or are undergoing PCI , according to the
current ACC/AHA and ESC guidelines.
 However,despite the administration of dual
antiplatelet therapy, some patients do develop
recurrent cardiovascular ischemic events, with
stent thrombosis being the most catastrophic.
ASIAN POPULATION

 This may be secondary to heterogeneity in
response of individual patients to each of
these drugs.
 Varying incidence of aspirin and clopidogrel
resistance could be one of the causes of stent
thrombosis in post-PCI patients.
 The lack of standard definition of resistance
as well as its diagnosing modality has
hampered the identification and the treatment
of this clinical entity.
ASIAN POPULATION

ASIAN POPULATION

 Aspirin resistance was defined by the
presence of at least 2 of the following 3
criteria:
0.5-mg/ml AA-induced platelet aggregation
> 20%,
10-mol/l ADP-induced aggregation > 70%,
and
 Verify Now ARU > 550.
 Aspirin semi-responders are defined as
those meeting only one of the criterias.ANTIPLATELET RESISTENCE in
ASIAN POPULATION

Classification of aspirin
resistance
 Weber et al classified aspirin resistance into 3 types based
on biochemical and functional in vitrostudies.
 In aspirin responders, an oral intake of 100 mg/day of
aspirin for 5 days resulted in more than 95% inhibition of
thromboxane synthesis and also in the inhibition of collagen
induced platelet aggregation measured in vitro.
 In type I resistance, there was no inhibition of either
thromboxane synthesis or collagen induced platelet
aggregation with oral aspirin intake for 5 days.
 However, the in vitro addition of aspirin into the platelet rich
plasma showed remarkable change in parameters.
 This suggests considerable variation in pharmacokinetics
with low dose aspirin, and hence type I resistance is called as
‘pharmacokinetic type resistance’.
ASIAN POPULATION

 In type II resistance, both the platelet
functions were altered neither by the oral
intake of aspirin nor by the in vitro addition
of aspirin.
 The mechanism of this type of resistance
is unclear, but may relate to genetic
polymorphism of the enzymatic pathway
and its sensitivity to aspirin – hence called
as ‘pharmacodynamic type resistance’.
ASIAN POPULATION

 In type III resistance (pseudoresistance), oral treatment
resulted in the inhibition of thromboxane synthesis.
 However, this was not accompanied by the expected inhibition
of platelet aggregation in response to collagen.
 The lack of effect of platelet aggregation in response to
collagen despite thromboxane synthesis was not corrected by
the addition of aspirin in vitro.
 This is labelled as ‘pseudoresistance’, since aspirin did exert
its putative effect of inhibition of platelet thromboxane
synthesis, but failed to alter other important in vitro antiplatelet
effects.
 This may be due to increased sensitivity of platelets to
collagen.
ASIAN POPULATION

 patients with type I resistance may
benefit from increasing the dose of
aspirin, while type II and III resistance
need other antiplatelet drugs like
clopidogrel.
 But, clinical significance of this
classification has not been prospectively
tested.
ASIAN POPULATION

Management of aspirin
resistance
 Recent observations have demonstrated
that the primary cause of aspirin resistance
is poor compliance to medication.
◦ When performing a platelet function test
assessing for aspirin responsiveness it is
imperative to know if the patient is compliant
with treatment.
◦ In addition, it is recommended to use platelet
function tests specific for COX-1 .ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 The second most important factor in the
management of aspirin-resistant patients is
whether the patients are receiving co-
medication, especially OTC products
such as ibuprofen, which may interfere
with COX-1 acetylation.
ASIAN POPULATION

 Some have considered increasing the
dose of aspirin in resistant patients.
 However, increasing the dose of aspirin has
not been associated with an increase in
COX-1 inhibition, as assessed by specific
assays (Chest 2001;119(suppl):39S– 63S).
 ADRs may also develop (GI disorders,
bleeding, etc.)
ASIAN POPULATION

CLOPIDOGREL
ASIAN POPULATION

 It is well established that the antiplatelet
response to clopidogrel varies widely
among patients.
 Patients who display little attenuation of
platelet reactivity under clopidogrel
therapy are recognized as low- or non-
responders, or clopidogrel-resistant.
ASIAN POPULATION

Variable Clopidogrel Response
Antiplatelets and Antithrombotics after
DES: What Next? ;
At 5 Days
UA Patients* (n = 32)
Responders
47%
Low responders
32%
Nonresponders
22%
*Received an oral loading dose of 300 mg of clopidogrel followed by 75 mg daily.
Gurbel PA, et al. Circulation. 2003;107(23):2908-2913; Lau WC, et al. Circulation. 2004;109(2):166-171.

Clopidogrel resistance -
definition
 “the persistent activity of clopidogrel target
(i.e. P2Y12 receptors of the platelet) despite
an adequate antiplatelet regime”.
 Clopidogrel non-responsiveness is reported to
vary between 4% and 44% among different
populations.
 In laboratory terms, the definition of
clopidogrel resistance varies depending on
the different tests used for quantifying
residual platelet reactivity and the selection of
cut-off values. ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 More specifically, when light
transmittance aggregometry is used, the
optimal threshold for defining high
residual platelet reactivity is set as a
percentage of platelet inhibition lower
than 20%, or induced maximal platelet
aggregation greater than 50%.
 The point of- care assay VerifyNow©
P2Y12 is most commonly used with a
cut-off value that ranges in different
research groups from 230-240 platelet
reactivity units (PRU). ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 The prevalence of clopidogrel non-
response has been evaluated between
4% and 30% 24 hours after its
administration.
(J Am Coll Cardiol 2004;43:1127–1129, Am
J Cardiol 2004;93:456–458).
ASIAN POPULATION

Mechanisms of clopidogrel
response variability
 The mechanisms underlying
interindividual variability in response to
clopidogrel have not been defined but
are probably multifactorial.
J Am Coll Cardiol 2007;49:1505–1515
Am J Cardiol 2009;103[suppl]: 27A–34A
Thromb Res 2007;120:311-321
ASIAN POPULATION

 Mechanisms of clopidogrel resistance:
PK interactions
 Is omeprazole the bad guy?
 Are all PPIs the bad gang?
ASIAN POPULATION

 Gastric ulcer and duodenal ulcer are
known undesirable effects of
clopidogrel. This may lead to the use
of PPI
ASIAN POPULATION

STATINS
 Early studies suggested a possible negative
effect on clopidogrel’s efficacy from the use of
statins, possibly due to the shared CYP3A4
enzymatic pathway between statins and
clopidogrel.
 However, ample research data, taking
advantage of new point-of-care methods for
examining platelet aggregation, have clearly
ruled out a significant interaction between
statins and clopidogrel, concluding that the
concomitant use of statins is safe.ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 Genetic polymorphism exists for CYP2C19
expression.
 CYP2C19 alleles are *1, *2, *3, *4, and *7.
 Allele *1 is normal; *2, *3, and *4 are reduced;
and *7 is increased enzymatic activity.
 Depending on ethnicity, 30–55% of persons
harbor a loss-of-function of the CYP2C19 allele
(CYP2C19*2).
 Compared with noncarriers, CYP2C19*2 carriers
treated with clopidogrel had lower levels of active
clopidogrel metabolite. ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 In the GIFT study, the genetic substudy of
GRAVITAS, blood samples were tested for
40 polymorphisms, and these correlated
with the results of on-treatment VerifyNow
P2Y12 assay.
 HRPR was increased 11-fold in
homozygotes and increased 62% in
heterozygotes for the CYP2C19*2 gene,
compared with noncarriers.
 The study did not find any association of the
CYP2C19*17 gain-of-function gene with
reduced on-treatment platelet reactivity.ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 Shetkar et al. in their study of
CYP4502C19 polymorphism in 110 Indian
patients with coronary artery disease (CAD)
shows that 47.23% of the patients are *2
loss-of-function mutation and 35.45% are *7
gain-of-function mutation.
 They conclude that CYP2C19 gene
polymorphisms are common in Indian
population, but loss-of-function mutation
status did not affect the clinical outcome ofANTIPLATELET RESISTENCE in
ASIAN POPULATION

 Polymorphism also exists in paraoxonase-
1 (PON-1), a crucial enzyme responsible
for clopidogrel bioactivation, but studies
have failed to confirm an association
between PON-1 polymorphism and on-
clopidogrel platelet reactivity using
VerifyNow.
ASIAN POPULATION

 The results of meta-analyses are conflicting.
 A report on 9 studies in 9,685 patients undergoing
PCI and another involving 10 studies in 11,959
patients, both concluded that reduced-function
CYP2C19 alleles expose patients treated with
clopidogrel to increased risk of cardiovascular
events.
 However, 2 recent meta-analyses (not confined to
stented patients) showed that although there was an
association between CYP2C19 genotype and
clopidogrel responsiveness, genotype was not
associated with cardiovascular events, with the
possible exception of ST in the subgroup of patients
undergoing PCI, where ST was associated with
CYP2C19 loss-of-function alleles
ASIAN POPULATION

Light transmission and
impedance aggregometry assays
 Light transmission aggregometry measures optical density of
plasma after platelet aggregation with an agonist.
 The problem with this test is lack of standardization as to the
choice of agonist/s and their concentration.
 Furthermore, there is a marked variability in aggregation
response to different agonists.
 Impedance aggregometry utilizes whole blood instead of plasma
and measures electrical impedance instead of light transmission.
 This test assesses the role of blood components including
leukocytes and clotting factors besides platelets in thrombus
formation as a mild electrical current is passed through the whole
blood.
ASIAN POPULATION

 Aspirin hyporesponsiveness is defined as
more than 10%-20% with light
transmittance aggregometry and more
than 0 ohms with impedance
aggregometry.
ASIAN POPULATION

VERIFY NOW
 The VerifyNow© P2Y12 assay is a point-
of-care device that uses an automated
analyzer with single use, disposable
assays.
 This assay is simple, accurate and fast
in measuring individual response to
antiplatelet agents.
ASIAN POPULATION

VERIFYNOW Point of Care Test
It measures the rate and extent
of changes in light
transmittance caused by
platelet aggregation in a pre-set
tube in which whole blood in
placed
It thus mimics light transmission
aggregometry
Samples containing inhibited
platelets will produce low level
of light transmittance while
samples containing normally
functioning platelets will
aggregate more rapidly,
resulting in higher level of light
transmittance

PFA-100® assay
 This test uses cartridges coated with platelet
agonists (either collagen/ADP or
collagen/epinephrine).
 The time for platelet plug to close the central
opening (closing time) is used as a measure of
platelet reactivity.
 “Aspirin resistance” is defined as: closing time <
193 s using collagen/epinephrine, and < 121 s
using collagen/ADP as agonists.
 This test is unfortunately not aspirin-specific.
 It correlates well with light transmission

TXA2 metabolites
 Serum TXB2 and urinary 11-dehydro-TXB2 are
metabolites of TXA2
 These are COX-1 dependent tests and are not
platelet specific and do not necessarily reflect
platelet reactivity.
 Serum TXB2 reflects TXA2 formation by
endothelial cells and leukocytes in addition to
platelets.
 Urinary 11-dehydro-TXB2 usually requires 24 h
urine collection and reflects TXA2formation by
renal tissues besides platelets and leukocytes.ANTIPLATELET RESISTENCE in
ASIAN POPULATION

The VASP test: A Specific Test to
Measure P2Y12 Inhibition
•VASP is not phosphorylated at basal
state
•PGE1 activates VASP
phosphorylation
•ADP inhhibits VASP phosphorylation
via the P2Y12 receptor
•Thus high VASP = active form of
P2Y12 receptor
•Low VASP (high VASP-P) =
inhibition of P2Y12 receptor

 The recently presented POPULAR study
compared the findings of 6 different platelet
tests showed a high correlation between
the VerifyNow assay and, to a lesser extent,
LTA with the plasma level of the active
metabolite of clopidogrel was described,
suggesting that these may be the preferred
laboratory tests for evaluating patient
response to clopidogrel.
ASIAN POPULATION

Clinical significance of in vitro
clopidogrel low
responsiveness
 Several studies have shown that inadequate
platelet inhibition leads to adverse clinical
outcomes, including recurrent ischemic
cardiovascular events, stent thrombosis and
periprocedural myocardial infarction.
 These studies have been performed in
different subgroups of patients undergoing
PCI for ST-elevation myocardial infarction
(STEMI) or non-STEMI, as well as elective
PCI procedures.
ASIAN POPULATION

 Small, randomized studies have
demonstrated proof of principle that PFT-
guided therapy reduces the risk of
cardiovascular events compared with
conventional therapy.
ASIAN POPULATION

 Snoep et al. systematically reviewed in the meta-
analysis investigating the association between
clopidogrel nonresponsiveness and clinical
outcome by evidencing an increased risk of clinical
recurrences for those with residual platelet
reactivity under clopidogrel treatment and he states
that laboratory clopidogrel nonresponsiveness
is a marker of increased risk of adverse
cardiovascular outcomes in patients undergoing
PCI with stenting.
ASIAN POPULATION

 The GRAVITAS trial, the first large-scale
clinical trial, designed to examine
whether adjustment of clopidogrel
therapy, on the basis of platelet function
testing using a point-of-care assay, safely
improves outcome after PCI with drug-
eluting stents in clopidogrel resistant
patients, did not show any superiority
of 150 mg vs. 75 mg of clopidogrel
ASIAN POPULATION

 RESULTS - Platelet-function testing
with antiplatelet therapy adjustment
before and after coronary stenting
does not improve clinical outcome as
compared with conventional treatment
without platelet-function testing.
ASIAN POPULATION

 The results of ARCTIC are consistent with
that of GRAVITAS and TRIGGER-PCI in
that out-of-hospital event rates in patients
undergoing nonurgent PCI are in general
low, irrespective of OTR.
 The clinical efficacy of PFT in patients
undergoing PCI for ACS remains
unaddressed by these trials.
ASIAN POPULATION

 Therefore, it is unlikely that functional
testing may provide useful information
to guide clinical decision making in
most individual patients for the
prevention of ischemic events.
ASIAN POPULATION

Rationale for Clinical Use
 In the absence of definitive RCTs, the
prognostic utility of PFT and genotyping
supports an individualized approach to
their use in practice.
ASIAN POPULATION

How to minimize the risk of
clopidogrel resistance
ASIAN POPULATION

 In patients undergoing PCI a loading dose of 600 mg
clopidogrel was associated with a higher level of
platelet inhibition, lower mean post-treatment reactivity
to adenosine diphosphate (ADP), and a lower
incidence of non-responsiveness when compared to a
300 mg dose.
 In the ISAR-CHOICE study, however, there was no
additional effect regarding clopidogrel metabolite levels
and platelet inhibition between the 600 mg and the 900
mg loading dose
ASIAN POPULATION

 The authors concluded that a single dose of
clopidogrel higher than 600 mg was not
associated with additional significant
suppression of platelet function; this was
probably due, after analyzing the
pharmacokinetic profile and metabolites, to
limited clopidogrel absorption.
 The 600 mg dose appears to achieve
maximum inhibition more rapidly than the
300 mg dose. ANTIPLATELET RESISTENCE in
ASIAN POPULATION

 The ARMYDA-2 study showed the benefit
of 600 mg of clopidogrel when compared
with 300 mg of clopidogrel as pretreatment
in reducing periprocedural myocardial
infarction in patients undergoing PCI.
 The utility of increasing the dose of
clopidogrel has been further supported by
the findings in the ALBION trial.
ASIAN POPULATION

 The OASIS-7 trial randomized 25,087 patients with unstable angina or
acute MI to a high dose regimen (600 mg loading dose of clopidogrel,
followed by 150 mg per day for 1 week) or the standard regimen (300 mg
on the first day followed by 75 mg/day).
 At 30 days, the primary endpoint, the combined rate of cardiovascular
death, MI, and stroke, occurred similarly in 4.4% of patients on the
standard-dose clopidogrel and in 4.2% of patients on the high dose.
 However, among the two-thirds of the study patients undergoing PCI, the
risk of stent thrombosis was reduced by 30% and the risk of MI was
reduced by 22% in the group that received the high dose, compared to
the group that received the standard dose.
 The highdose group had more major bleeding, but there was no increase
in intracerebral or fatal bleeds.
 No benefit was found in the group on a higher dose who did not have
PCI.
ASIAN POPULATION

Prasugrel
 Prasugrel is a novel thienopyridine introduced for the
treatment of acute coronary syndromes.
 It is also a prodrug that, after absorption, is converted
to its active metabolite, which targets the P2Y12 ADP
platelet receptors.
 In contrast to clopidogrel, it is mainly metabolized by
cytochrome isoenzymes CYP3A and CYP2B6, though
there is a lesser contribution from CYP2C9 and
CYP2C19.
 So CYP2C219 has minimal influence on the formation
of prasugrel’s active metabolite.
ASIAN POPULATION

 Prasugrel quickly demonstrated that it
achieves higher and more rapid inhibition
of platelet aggregation and a greater
reduction of pharmacodynamic non-
responders, compared with the standard
clopidogrel dose of 75 mg.
ASIAN POPULATION

 Wiviott et al showed, in a randomized crossover study of 201
post-PCI patients, that prasugrel in a loading dose (LD) of 60
mg and 10 mg maintenance dose (MD) achieved higher and
more consistent levels of platelet inhibition than clopidogrel
at 600 mg LD and 150 mg MD.
 The recent ACAPULCO study reinforced this observation by
proving prasugrel’s superiority in platelet inhibition compared to
high-dose clopidogrel MD 150 mg or 900 mg LD.
 Similar results have been described in clopidogrel resistant
patients, with the superiority of prasugrel being more apparent
in patients carrying the CYP2C19*2 loss-of-function allele.
ASIAN POPULATION

 In a small though challenging study, Pena et al
described clopidogrel responsiveness in 7 patients
who presented with stent thrombosis.
 The sequential increase of clopidogrel maintenance
dose up to 300 mg could not achieve the levels of
inhibition achieved by prasugrel.
 All 7 patients, 6 of whom had at least one poor-
metabolizing allele of CYP2C19, did not respond to
150 mg clopidogrel and 2 of them remained resistant
even to a 300 mg clopidogrel maintenance dose,
whereas prasugrel achieved adequate platelet
inhibition in all of them
ASIAN POPULATION

 In TRITON-TIMI-38 trial, it has shown that
both the loading dose and the maintenance
dose of prasugrel were superior to clopidogrel
for the reduction of ischemic events.
 This result emphasizes the importance of
maintaining high levels of inhibition of platelet
aggregation via P2Y12 receptor inhibition, not
only for the prevention of periprocedural
ischemic events, but also during long-term
follow-up.
ASIAN POPULATION

TICAGRELOR
 Ticagrelor is an oral, direct-acting drug which, like the
thienopyridines, targets the ADP receptor P2Y12.
However, unlike clopidogrel and prasugrel, the receptor
inhibition is reversible.
 The PLATO trial compared ticagrelor (180 mg loading
dose, 90mg twice daily thereafter) and clopidogrel
(300-600 mg loading dose, 75 mg daily thereafter) in
18,624 patients admitted to hospital with an acute
coronary syndrome.
 The ticagrelor group had a significantly lower
occurrence of cardiovascular events, but was
associated with a higher rate of major bleeding that
was not related to coronary artery bypass grafting.
ASIAN POPULATION

 Recently, the RESPOND Study suggested that
ticagrelor therapy might be an appropriate approach
to overcome non-responsiveness to clopidogrel in
patients with stable coronary artery disease.
 Under ticagrelor treatment, platelet reactivity was
below the cut-off points previously associated with
ischemic in 98% to 100% of patients versus 44% to
76% of patients after clopidogrel therapy.
 Furthermore, the antiplatelet effect of ticagrelor was
the same in responders and nonresponders
ASIAN POPULATION

CANGRELOR
 Cangrelor, another reversible non-thienopyridine ADP
receptor P2Y12 inhibitor, administered intravenously, was
assessed in the CHAMPION-PLATFORM and the
CHAMPION-PCI trials. Both failed to show superiority
compared to clopidogrel.
 In vitro, however, the addition of even a sub-therapeutic
dose of cangrelor to the platelet-rich plasma of clopidogrel-
pretreated patients resulted in an additional reduction of
ADP-induced platelet aggregation as measured with the LTA.
 Moreover, cangrelor treatment was able to reduce the inter-
individual variation observed in clopidogrel-inhibited
platelet aggregation.
ASIAN POPULATION

 In CHAMPION PHOENIX trial, cangrelor
significantly reduces the rate of ischemic
events, including stent thrombosis, during
PCI with no significant increase in severe
bleeding.
 In addition, cangrelor is an intravenous, fast-
acting, potent direct-acting P2Y12
antagonist which blocks platelet aggregation
more completely than clopidogrel and also
does not require hepatic metabolism for
activation.
ASIAN POPULATION

 Triple antiplatelet therapy with the addition of cilostazol has
been proved in several large-scale studies to be more efficient
in preventing adverse clinical events, especially stent
thrombosis, without an increase in side effects compared to
standard dual antiplatelet therapy.
 By laboratory means, cilostazol has also been reported to
increase platelet inhibition compared to standard dose
clopidogrel in studies using the VerifyNow assay.
 Adding cilostazol to standard clopidogrel also appears to be
more effective in platelet inhibition, even compared to a high
maintenance dose of clopidogrel (150 mg/d), as has been
demonstrated by the ACCEL-RESISTANCE study.
ASIAN POPULATION

Antiplatelet resistence in INDIAN
population
 The first prospective descriptive study of antiplatelet drug resistance
in Indian patients by using VerifyNow test.
 The study includes total of 200 patients, 87% are males and 13%
are females.
 Platelet function test (PFT) is done in 5–10 days of the post-PCI.
 The prevalence of aspirin resistance is 22% in our coronary
intervention patients.
 There is no statistically significant difference of aspirin resistance
with gender, age, and diabetes in our patients.
 The prevalence of clopidogrel resistance is 32.5% in our coronary
intervention patient.
 Large number of female patients are (38%) resistant to clopidogrel
(p = 0.001) in our study and this is similar to other international
studies.
 There is no statistically significant difference of clopidogrel
resistance with age and diabetes in our patients.
ASIAN POPULATION

Possibilities To Improve
Clinical Usefulness Of PFTs
 1.Use of native, instead of citrate-
anticoagulated blood.
 2.Use of a global stimulus - Arterial
thrombosis occurs at pathological high shear
stresses (>10,000 s−1), which create rapid
and strong bonds between platelets without
prior activation.
 The shear rate in IMPACT-R is only 1,800
s−1(therefore, this test measures platelet
adhesion but not aggregation) and in PFA-
100 is generously estimated at 5,000 to
6,000 s−1.
ASIAN POPULATION

 Platelet interaction with von Willebrand
factor, thrombin generation by shear-
activated platelets, and shedding of
microparticles by shear-activated platelets
(a major contributor to thrombin
generation) occur only at shear rates
exceeding 10,000 s−1, and aggregates thus
formed are unstable until the shear rate is
≥20,000 s−1.
ASIAN POPULATION

 3. Involvement of platelet-dependent
thrombin generation - current point-of-care
PFTs most frequently employ citrate-
anticoagulated blood, and at the very low
plasma calcium levels therein, platelets do
not generate thrombin, and consequently,
the effect of thrombin on platelets is also
attenuated.
ASIAN POPULATION

 4. Clear definition of safety/efficacy
thresholds and evaluation of clinical
usefulness - PFT should be undertaken
not only when practicable, but when it can
discriminate sensitively between high- and
low-risk patients, can lead to alterations in
treatment that improve outcomes and is
cost effective
ASIAN POPULATION

 5.Quality control:- Barriers to adoption of
standardized quality assurance for PFTs
include:
1) The need for frequent blood samples, both
from many normal donors and affected
patients, which maybe practically, clinically,
and ethically challenging;
2) Time-delay issues, due to transportation, or
with tests employing non-anticoagulated
blood. ANTIPLATELET RESISTENCE in
ASIAN POPULATION

CURRENT GUIDELINES
ASIAN POPULATION

FUTURE DIRECTION AND
CLINICAL CONSIDERATION
 A PFT providing both the optimal range of
platelet reactivity necessary to prevent
thrombotic events, as well as the range to
avoid excessive bleeding, would therefore
be highly desirable.
 PFTs have the most to offer in detecting
those who are at highest risk of future
cardiovascular events.
ASIAN POPULATION

 We have to assess whether individualization of
antiplatelet therapy based on the results of PFT will
alter clinical outcome, large randomized clinical trials should be
performed in the highest-risk groups [such as ACS patients with high
GRACE so that these are adequately powered to detect outcomes.
 The optimal timing of PFT is important, especially in ACS.
Baseline assessment is often not possible before initiation of treatment,
because many, especially those with ST-segment elevation myocardial
infarction, will have received DAPT and often a thrombin inhibitor by the
time of presentation. Despite testing just before hospital discharge,
administration of earlier anticoagulants may still distort PFT results.
 Assessing patients at 6-week follow-up to guide therapy, after the acute
inflammatory response has settled, has the obvious limitation that the first
4–6 weeks after an ACS is actually the highest thrombotic risk period.
 Whether a single result or serial testing is required for
ongoing therapy is also unclear.
ASIAN POPULATION

 In the acute setting, dosages can certainly be increased,
which, with many agents, can improve PFT results, but there
are also many newer agents that reduce MACE in high-risk
groups, such as ticagrelor and prasugrel, irrespective of PFT.
 The clinical utility of switching drugs on the
basis of PFT results in reducing adverse events could not
be demonstrated in stable CAD patients, perhaps due to the
low event rate after PCI with contemporary DES in this setting.
 Whether it is clinically more cost effective to limit prasugrel and
ticagrelor to patients with HRPR, or whether it is more
efficacious to administer these drugs for all licensed
indications without performing PFT, remains to be established.
ASIAN POPULATION

THANK YOU
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Antiplatelet resistence - significance and how to deal ?

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Antiplatelet resistence - significance and how to deal ?

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