disclosures update on oral antiplatelet therapy in...

Ty J. Gluckman, MD, FACC

Providence St. Vincent Heart and Vascular Institute, Portland, Oregon

Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University,

Baltimore, Maryland

Update on Oral Antiplatelet Therapy in Coronary Artery Disease

DisclosuresDisclosures

Grant/Research Support: None

Consultant/Advisory Board: None

Major Stockholder: None

Speakers Bureau: Eli Lilly/Daiichi-Sankyo Partnership, Bristol-Myers Squibb

How does hemostasis occur and when is it not desired?

ThrombinThrombin

AGGREGATION

FibrinFibrin

HemostaticHemostaticClotClot

ClottingClottingPlatelet AggregationPlatelet Aggregation

0 min0 min 10 min10 min5 min5 min

SECONDARYSECONDARY

PRIMARYPRIMARY

COAGULATION

Adapted from Ferguson JJ et al. Antiplatelet Therapy in Clinical Practice. 2000:15-35

How is Normal How is Normal HemostasisHemostasis Achieved?Achieved?

Libby P. Circulation 2001;104:365-72

When is When is ““NormalNormal”” HemostasisHemostasis not Desirable?not Desirable?

Davies MJ. Heart 2000;83:361-366

How can hemostasis be inhibited in at-risk individuals?

FDA Approved Oral FDA Approved Oral AntiplateletAntiplatelet AgentsAgents

Ticid FDA ApplicationPlavix package insertEffient package insertBrilinta package insertLacy CF et al. Drug Information Handbook. 9th ed. Hudson, OH: 2001Angiolillo D, et al. Am Heart J. 2008;156:S1-S2

Drug Class Mechanism of Action Half-Life Indication

Aspirin Salicylates Irreversible inactivation of COX-1

5–6 hours Pain, fever, inflammation, prevention of MI, & stroke

Ticlopidine Thienopyridine P2Y12 receptor antagonist

24 hours Stroke prevention & stentthrombosis

Clopidogrel Thienopyridine P2Y12 receptor antagonist

8 hours (inactive

metabolite)

Prevention of ischemic events in patients with: History of MI, stroke, or PAD and in ACS

patients with UA/NSTEMI or STEMI

Prasugrel Thienopyridine P2Y12 receptor antagonist

7 hours Prevention of ischemic events in ACS patients managed with PCI

Ticagrelor Cyclopentyl-triazolopyrimidine

P2Y12 receptor antagonist

7 hours Prevention of ischemic events in patients with ACS

ACS=Acute coronary syndrome, COX-1=Cyclooxygenase-1, MI=Myocardial infarction; NSTEM=Non-ST-segment elevation myocardial infarction, PAD=Peripheral artery disease; PCI=Percutaneous coronary intervention, STEMI=ST-segment elevation myocardial infarction, UA=Unstable angina

ThrombinSerotoninEpinephrineCollagen

ADPADP

Activation

TXATXA22

ActivatedPlatelet

COX

Degranulation

Aspirin

αα δδ

Gp IIb/IIIafibrinogenreceptor

To neighboringplatelet

P2Y12Receptor

Antagonist

Platelet agonistsADP, ATPserotoninCalcium, magnesium

Adhesive proteinsthrombospondinfibrinogenp-selectinvWF

Coagulation factorsfactor V, XI, PAI-1

Inflammatory factorsPF4, CD40 ligand, PDGF

Adapted from Ferguson JJ et al. In: Antiplatelet Therapy in Clinical Practice. London: Martin Dunitz;2000:15-35

Antagonizing the Platelet Side of Antagonizing the Platelet Side of HemostasisHemostasis

What are the benefits and limitations of using antiplatelet therapy in at-risk

individuals?

What is the Efficacy of Aspirin in Secondary Prevention?What is the Efficacy of Aspirin in Secondary Prevention?

Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86

Effect of antiplatelet treatment* on vascular events**

*Aspirin was the predominant antiplatelet agent studied, **Include MI, stroke, or death

Category % Odds ReductionAcute MIAcute CVA Prior MIPrior CVA/TIAOther high riskCVD

(e.g. unstable angina, heart failure)PAD

(e.g. intermittent claudication)High risk of embolism (e.g. Afib)Other (e.g. DM)

All trials

1.00.50.0 1.5 2.0Control betterAntiplatelet better

What is the Efficacy of Dual What is the Efficacy of Dual AntiplateletAntiplatelet Therapy?Therapy?

Rates of Ischemic Events

The CURE Trial Investigators. NEJM 2001;345:494-502Steinhubl S et al. JAMA 2002;288:2411-20Sabatine MS et al. NEJM 2005;352:1179-1189COMMIT Collaborative Group. Lancet. 2005;366:1607-1621Bhatt DL et al. NEJM 2006;354:1706-1

A=Aspirin, C=Clopidogrel, P=Placebo (*P=Prasugrel in the TRITON-TIMI 38 trial), T=Ticagrelor

Trial Primary End Point

A + C A + P (T) P-value NNT

CURE CVD, MI, CVA 9.3% 11.4% <0.001 48CREDO CVD, MI, CVA 8.5% 11.5% 0.02 33COMMIT CVD, MI, CVA 9.2% 10.1% 0.002 111

CHARISMA CVD, MI, CVA 6.8% 7.3% 0.22 --TRITON-TIMI 38 CVD, MI, CVA 12.1% 9.9%* 0.0004 45

PLATO CVD, MI, CVA 11.7% 9.8% <0.001 53

CVA=Stroke, CVD=Cardiovascular death, MI=Myocardial infarction, UR=Urgent revascularization

What are the Risks of What are the Risks of AntiplateletAntiplatelet Therapy?Therapy?Rates of Major Bleeding

The CURE Trial Investigators. NEJM 2001;345:494-502Steinhubl S et al. JAMA 2002;288:2411-20Sabatine MS et al. NEJM 2005; 352:1179-1189


Trial Aspirin Dose A + C A + P (T) P-value NNHCURE 75-325 mg 3.7% 2.7% 0.001 100

<100 mg 2.6% 2.0% 167100-200 mg 3.5% 2.3% 83

>200 mg 4.9% 4.0% 111CREDO 81-325 mg 1.2% 0.8% 0.28 --COMMIT 162 mg 0.58% 0.53% 0.59 --

CHARISMA 75-162 mg 1.7% 1.3% 0.09 --TRITON-TIMI 38 75-325 mg 1.8% 2.4%* 0.03 167PLATO (TIMI)** 75-325 mg 7.7% 7.9% 0.57 --

COMMIT Collaborative Group. Lancet. 2005; 366:1607-1621

Bhatt DL et al. NEJM 2006;354:1706-17

**Among patients not undergoing CABG, the TIMI rates of major bleeding were 2.2% (clopidogrel) vs. 2.8% (ticagrelor), p=0.02, NNH=167

= Good Outcome

= Intermediate Outcome

= Bad Outcome

Outcomes from a Study

Risk Stratification

Mean Treatment Difference

Do These Results Apply Equally to Everyone?Do These Results Apply Equally to Everyone?

Courtesy of John Spertus, MD

What risks are associated with antiplatelet withdrawal?

Risks Associated with Aspirin Withdrawal Risks Associated with Aspirin Withdrawal

Collet JP et al. Circulation 2004;110:2361-7

Prospective cohort of 1,358 patients with an acute coronary syndrome stratified by oral antiplatelet status as a non-user, prior user, or recent withdrawer*

Withdrawal of aspirin is associated with increased CV risk*Defined as cessation within the last 3 weeks, with 96% of patients on aspirin

Risks Associated with Risks Associated with ClopidogrelClopidogrel Withdrawal Withdrawal

Incidence of Death or Acute Myocardial Infarction

Ho PM et al. JAMA 2008;532-9

CV=Cardiovascular, PCI=Percutaneous coronary intervention

Retrospective cohort of 3,137 patients with an acute coronary syndrome treated with clopidogrel after discharge

Withdrawal of clopidogrel leads to early increased CV risk

Risks Associated with Risks Associated with AntiplateletAntiplatelet Withdrawal Withdrawal

Curfman GD et al. NEJM 2007;356:1059-60

Stent Thrombosis

• Most cases (60%) occur within the first 30 days, regardless of stent type

• Stable angina - 30 day: 0.3-0.5%- 1 year: 0.6-1.7%

• ACS- 30 day: 1.2-3.1%- 1 year: 4.3-5.8%

How should antiplatelet therapy be managed perioperatively?

High-risk acute coronary syndrome or high-risk anatomy

Perioperative Management of Antiplatelet TherapyPerioperative Management of Antiplatelet Therapy

Bleeding risk of surgeryLow PCI with continued dual

antiplatelet therapy

Not Low

Timing of

Surgery14-29 days >365 days30-365 days

POBA BMS DES

Time Since PCI

Delay for elective or nonurgent surgery

Proceed to the OR with aspirin

Delay for elective or nonurgent surgery

Proceed to the OR with aspirin

<14 days >14 days >30-45 days <30-45 days <365 days >365 days

BMS=Bare metal stent, DES=Drug eluting stent, OR=Operating room, POBA=Plain old balloon angioplasty

What is the optimal duration of dual antiplatelet therapy?

�

Dea

th/M

I (%

)

Drug Eluting Stent

7.29

6

3

0

3.1

P=0.02

6.05.5

P=0.70

6 months of DAP 12 months of DAP

Bare Metal Stent

How long should a P2YHow long should a P2Y1212 Inhibitor be Used?Inhibitor be Used?

Observational study of 4,666 patients undergoing percutaneous coronary intervention stratified by type of stent and self-reported use of

clopidogrel at 6 and 12 months

Longer term clopidogrel provides benefit following a DES

24 months of DAP

�

�

P<0.001

4.5

0.0�

�

3.6 4.7

P=0.44

Eisenstein EL et al. JAMA 2007;297:159-68

DAP=Dual antiplatelet therapy, DES=Drug eluting stent, MI=Myocardial infarction

�

Haz

ard

Rat

io

Major Ischemic Events

3

2

1

0

2.96

EXCELLENT REAL-LATE/ZEST-LATE

Bleeding Events

PRODIGY

�

�

2.17

1.12

2.56

1.73

1.02

How long should a P2YHow long should a P2Y1212 Inhibitor be Used?Inhibitor be Used?

Gwon HC et al. Circulation 2012;125;505-13 Park SJ et al. NEJM 2010;362:1374-82 Valgimigli M et al. Circulation 2012;125-2015-26 Kim BK et al. JACC 2012;2012;60:1340-8

DAP=Dual antiplatelet therapy, PCI=Percutaneous coronary intervention

Three separate randomized trials evaluating varied durations of dual antiplatelet therapy following PCI: EXCELLENT (6 vs 12 months), REAL-LATE/ZEST-LATE (12 vs 24 months), PRODGIGY (6 vs 24

months), and RESET (3 vs 12 months)

RESET

�

1.00

�

2.00

Should a P2YShould a P2Y1212 Inhibitor be Used for >1 Year?Inhibitor be Used for >1 Year?

Dual Antiplatelet Therapy (DAPT) Trial

Drug-Eluting Stents (n=15,000)Bare Metal Stents (n=5,000)

Placebo

Co-primary end point: Stent thrombosisCo-primary end point: MACCE

Major safety end point: Major bleeding

33-month follow-up

N=20,000 patientsTreated for 12 months with either

Clopidogrel or Prasugrel in addition to aspirin

Clopidogrel or Prasugrel for an extended 18 months of therapy

What role do drug-drug interactions play in contributing to variance in

response to antithrombotic therapy?

Perc

ent i

nhib

ition

of

plat

elet

agg

rega

tion

75

50

25

02

Aspirin before ibuprofenIbuprofen before aspirin

100

6 12 24

Aspirin and DrugAspirin and Drug--Drug Interaction (NSAIDs)Drug Interaction (NSAIDs)

Catella-Lawson F et al. NEJM 2001;345:1809-17

Assessment of platelet inhibition among a group of patients treated each morning with aspirin (81 mg) administered two hours before ibuprofen (400 mg) and the same medications administered in the reverse order

Ibuprofen competitively inhibits platelet inhibition by aspirin

Retrospective cohort of 8,205 patients after an ACS

ClopidogrelClopidogrel and Drugand Drug--Drug Interaction (PPI)Drug Interaction (PPI)

Ho PM et al. JAMA. 2009;301(9):937-944

ACS=Acute coronary syndrome, PPI=Proton pump inhibitor

Days

Sur

viva

l Pro

babi

lity

0 30 60 90 120 150 180 210 240 270 300 330 360 390

0.90

0.92

0.94

0.96

0.98

1.00

Placebo

Treated

Survival Curves for PPI Treated vs PlaceboComposite Cardiovascular Events

ClopidogrelClopidogrel and Drugand Drug--Drug Interaction (PPI)Drug Interaction (PPI)

Clopidogrel and the Optimization of GI Events Trial (COGENT)3,627 patients with an ACS or undergoing PCI randomized to fixed dose

combination clopidogrel (75 mg) and omeprazole (20 mg) in addition to aspirin (75-325 mg) vs. clopidogrel (75 mg) and aspirin (75-325 mg) for a

median of 133 days

Survival free of Composite GI Events

HR = 0.55, p=0.007 HR = 1.02, 95% CI = 0.70-1.51

Bhatt DL et al. NEJM 2010;363:1909-1917

Surv

ival

free

of C

ompo

site

CV

Even

ts

Days

Is there variability in how individuals respond to antiplatelet therapy?

= Good Outcome

= Intermediate Outcome

= Bad Outcome

Outcomes from a Study

Risk Stratification

Mean Treatment Difference

Do These Results Apply Equally to Everyone?Do These Results Apply Equally to Everyone?

Courtesy of John Spertus, MD

There Exists Variability in Response to AspirinThere Exists Variability in Response to Aspirin

Maree AO et al. JACC 2005;46:1258-63

*All cases of aspirin nonresponsiveness were eradicated by exogenous higher dose aspirin

Assessment of platelet responsiveness* among 131 individuals with coronary artery disease treated with low dose (75 mg) enteric coated aspirin

There is wide variability in response to aspirin

There Exists Variability in Response to There Exists Variability in Response to ClopidogrelClopidogrel

Trenk D et al. Clinical Pharmacology and Therapeutics 2012;92:476-485

Assessment of ex vivo platelet aggregation among 2040 patients undergoing elective coronary angiography following a clopidogrel 600 mg loading dose

There is wide variability in response to clopidogrel

Do genetic differences underlie variability in response to antiplatelet

therapy?

IsIs There a Genetic Basis for Aspirin Variance?There a Genetic Basis for Aspirin Variance?

• COX-1 C22T• COX-1 C50T/A842G• COX-1 G128 A• COX-1 C644A• COX-1 C714A• COX-1 C10427A• COX-1 G1446A• COX-2 G765C• GP1a C807T• GP1bα C5T• GPIIIa T196C• GPVI T13254C• FXIII G34T• P2Y1 C893T• P2Y1 A1622G• P2Y12 H1/H2

Goodman T et al. British Journal of Clinical Pharmacology 2008;66:222-32

Collagen

Phospholipids

AA

TxA2

PlateletActivation

TxA2

Aspirin

Thrombin

?

?

COX-1

?Non-COX-1

Pathway

G12Gq

GPIIb/IIIaActivation

AggregationClot Formation

Is There a Genetic Basis for Is There a Genetic Basis for ClopidogrelClopidogrel Variance?Variance?

Trenk D et al. Clinical Pharmacology and Therapeutics 2012;92:476-485

ABCB1 3435C T1.Loss of function allele2.Mixed data whether TT homozygotes face increased CV risk

CYP2C19*21.Loss of function allele2.15% of Caucasians and Africans and 30% of Asians3.Impaired antiplatelet effect4.Increased CV risk

CYP2C19*171.Gain of function allele2.Mixed data whether there is a greater antiplatelet effect and increased bleeding risk

Should genetic testing be performed to guide the use of antiplatelet

therapy?

Goodman T et al. British Journal of Clinical Pharmacology 2008;66:222-32

Is There Benefit to Genetic Testing with Aspirin?Is There Benefit to Genetic Testing with Aspirin?

There is no polymorphism that predicts response to aspirin

Meta-analysis of 2,834 patients in whom candidate gene analyses were performed to assess for response to aspirin

Holmes MV et al. JAMA 2011;306:2704-2714

Meta-analysis of 4,341 patients reporting CYP2C19 genotype and platelet reactivity after a 600 mg loading dose of clopidogrel

Clopidogrel concentration* Platelet reactivity

*The expected mean active clopidogrel metabolite concentration in a white population for all individuals treated with 75 mg and for individuals with loss-of-function and normal/increased-function CYP2C19 alleles

Is There Benefit to Genetic Testing with Is There Benefit to Genetic Testing with Clopidogrel?Clopidogrel?


A meta-analysis of 9685 patients (91% underwent PCI and 55% had an ACS)who were treated with clopidogrel and in whom the carrier status of a mutant

CYP2C19*2 allele* was measured and clinical outcomes were tracked

CV death, MI, or ischemic stroke Stent thrombosis

Mega JL et al. JAMA 2010;304:1821-1830

ACS=Acute coronary syndrome, CV=Cardiovascular, PCI=Percutaneous coronary intervention

*Noncarrier (72%), 1 reduced function allele (26%), 2 reduced function alleles (2%)

333 patients with stable CV disease and known CYP2C19*2 genotype randomized to different maintenance doses of clopidogrel (75 mg vs 150

mg for noncarriers and 75 mg vs 150 mg vs 225 mg vs 300 mg for noncarriers) to assess the response to platelet reactivity

ELEVATE-TIMI 56

Mega JL et al. JAMA 2011;306:2221-2228


Is phenotyping of platelet function the answer?

Gold Standard to Assess Platelet ReactivityGold Standard to Assess Platelet Reactivity

http://practical-hemostasis.com/Platelets/platlet-function-testing-lta.html, Accessed 1/1/2010

Other Tests to Assess Platelet ReactivityOther Tests to Assess Platelet Reactivity

Available Tests to Assess Aspirin and P2Y12 Responsiveness

Gurbel PA et al. JACC 2007;50:1822-34

Test Able to Monitor Aspirin

Able to Monitor Thienopyridines

PFA-100 Yes NRVerifyNow Yes Yes

Plateletworks Yes Yes

Impact cone and platelet analyzer Yes YesThromboelastrogram Yes Yes

Activated platelet surface proteins (i.e., P-selectin) Yes Yes

VASP phosphorylation No YesSerum thromboxane B2 Yes No

Urinary 11-dehyrothromboxane B2 Yes No

NR=Not recommended

Marcucci R et al. Circulation 2009;119:237-242

Is There Benefit to Platelet Is There Benefit to Platelet PhenotypingPhenotyping??

A cohort of 683 patients presenting with an ACS and treated with PCI in whom point of care platelet function testing was performed

ACS=Acute coronary syndrome, PCI=Percutaneous coronary intervention

What more is needed to usher in the era of personalized medicine for

antithrombotic therapy?

Patients with low pre-treatment function and low inhibition have low post-treatment function and may be at Low Risk

(overestimation of risk based on low responsiveness)

Patients with high pre-treatment function and inhibition may still have high post-treatment function and may be at High Risk

(underestimation of risk based on normal responsiveness)

Post-treatment platelet function is a better predictor of ischemic events than platelet inhibition

(responsiveness)

Lack of Inhibition (Responsiveness) = High Risk

Samara et al. Thromb Res. 2005;115:89-94

Misconceptions About Misconceptions About AntiplateletAntiplatelet ResponsivenessResponsiveness Platelet Platelet PhenotypingPhenotyping to Tailor to Tailor AntiplateletAntiplatelet TherapyTherapy

Price MJ et al. JAMA 2011;305:1097-1105

DES=Drug eluting stent, LD=Loading dose, MD=Maintenance dose, PCI=Percutaneous coronary intervention

Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS] Trial

8,575 patients with high on-treatment platelet reactivity following PCI with a DES randomized to high dose (600 mg LD, 150 mg MD) versus

standard dose (75 mg MD) clopidogrel for 6 months

High dose clopidogrel does not reduce risk in those with HPR

Platelet Platelet PhenotypingPhenotyping to Tailor to Tailor AntiplateletAntiplatelet TherapyTherapy

ARCTIC Study2,440 patients with high on-treatment platelet reactivity following elective PCI with a DES randomized to standard therapy with clopidogrel versus

tailored therapy* periprocedurally and at 2-4 weeks post PCI

Price MJ et al. JAMA 2011;305:1097-1105

DES=Drug eluting stent, PCI=Percutaneous coronary intervention

Tailored therapy does not reduce risk in those with HPR after*Includes aspirin dose adjustment, clopidogrel dose adjustment, use of prasugrel and/or a GP Iib/IIIa inhibitor

Tailored Therapy

34.6

Standard Therapy

40

35

30

0

31.1

P=0.10Ris

k of

dea

th, M

I, st

ent

thro

mbo

sis,

st

roke

, or

urge

nt

reva

scul

ariz

atio

n (%

) Is such a personalized approach even needed?

0

5

10

30 60 90 180 270 360 450

HR 0.81P=.0004

Prasugrel Clopidogrel

HR 0.80P=.0003

HR 0.77P=.0001

Days

CV

deat

h, M

I, or

str

oke

%

12.1 (781)

9.9 (643) NNT=46

Wiviott SD, et al. NEJM 2007;357:2001-2015

Bleeding Events: Safety CohortClop, % Pras, % P

TIMI major 1.8 2.4 .03Life threatening 0.9 1.4 .01Nonfatal 0.9 1.1 .23Fatal 0.1 0.4 .002ICH 0.3 0.3 .74

Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel (TRITON-TIMI 38)

0

13,608 patients with high-risk ACS scheduled for PCI randomized to clopidogrel (300 mg LD and 75 mg MD) or prasugrel (60 mg LD and 10 mg MD) for a median

of 12 months

Prasugrel reduces ischemic events with greater bleedingACS=Acute coronary syndrome, ICH=Intracranial hemorrhage, LD=Loading dose, MD=Maintenance dose

Clinical Benefit of Greater Platelet Inhibition in ACSClinical Benefit of Greater Platelet Inhibition in ACS

Days after randomization0 60 120 180 240 300 360

121086420C

V D

eath

, MI,

or S

trok

e (%

) 9.811.7

HR 0.84, p=0.0003, NNT=53

Clopidogrel

Ticagrelor

Platelet Inhibition and Patient Outcomes (PLATO) Study18,624 patients with a moderate to high risk ACS randomized to clopidogrel

(300-600 mg LD and 75 mg MD) or ticagrelor (180 mg LD and 90 mg twice daily MD) for 12 months

Wallentin L et al. NEJM 2009;361:1045-7

Ticagrelor reduces ischemic events without greater bleeding

Bleeding Events: Safety Cohort**

Clop, % Ticag, %TIMI major/year 7.9 7.7PLATO major/year 11.6 11.2Fatal/year 0.3 0.3

ACS=Acute coronary syndrome, LD=Loading dose, MD=Maintenance dose

*Not currently approved by the FDA**No statistically significant differences were observed in bleeding rates overall

Clinical Benefits of Greater Platelet Inhibition in ACSClinical Benefits of Greater Platelet Inhibition in ACS

Efficacy and Safety of Greater P2YEfficacy and Safety of Greater P2Y1212 InhibitionInhibition

Rates of Ischemic Events in ACS patients undergoing PCI

Cannon CP et al. Lancet 2010;375:283-93Becker RC et al. Eur Heart J 2011;32:2933-44

**Rate of the primary end point in those with a planned invasive strategy (77% underwent PCI)

Trial Primary End Point

A + C A + P (T) P-value NNT

TRITON-TIMI 38 CVD, MI, CVA 12.1% 9.9%* 0.0004 45PLATO** CVD, MI, CVA 10.7% 9.0% 0.0025 59

CVA=Stroke, CVD=Cardiovascular death, MI=Myocardial infarction, UR=Urgent revascularization

Trial Aspirin Dose A + C A + P (T) P-value NNHTRITON-TIMI 38 75-162 mg 1.8% 2.4%* 0.03 167PLATO (TIMI)*** 75-325 mg 2.2% 2.8% 0.02 167

Rates of Major Bleeding in ACS patients undergoing PCI


***Rate of non-CABG related TIMI major bleeding

So what’s a clinician to do?

• Long term aspirin therapy is important in secondary prevention

• Dual antiplatelet therapy should be used after an ACS or PCI

• Current guidelines recommend at least 1 year of a P2Y12inhibitor

• Dual antiplatelet therapy increases the risk of bleeding

• Low dose aspirin (81 mg) should be used preferentially when given in conjunction with a P2Y12 inhibitor

• Withdrawal of antiplatelet therapy increases CV risk

• Attention to perioperative antiplatelet therapy is key to reduce CV risk

What do we know?What do we know? What do we know?What do we know?

• There is variability in patient response to antiplatelet therapy

• For aspirin

• Routine genotyping and phenotyping is not recommended

• For clopidogrel

• Genotyping for CYP2C19*2 can identify at risk individuals

• Platelet phenotyping can identify at risk individuals

• A higher LD/MD can achieve greater platelet inhibition

• Tailored therapy, however, hasn’t been shown to improve CV outcomes

• More potent antiplatelet therapy in ACS improves outcomes

QuestionsQuestions

disclosures update on oral antiplatelet therapy in...

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