Dapt duration

The optimal timing of initiation and duration of DAPT

Magdy El-MasryProf. of Cardiology

Tanta University

2015 Great Debate

? Single-antiplatelet therapy (SAPT) versus Dual-antiplatelet therapy (DAPT)

? Longer – versus shorter – duration DAPT

Answers to difficult questions in DAPT

Antiplatelet Agents—Oral P2Y12 Inhibitors

++ +++

+ Bleeding Risk

Spectrum of Coronary Artery Disease

AcuteCoronary Syndromes

StableCoronary Artery Disease

Moderate to high-risk NSTEACS as defined in PLATO: ≥2 of: (1) ischemic ST changes on ECG; (2) positive biomarkers;and (3) 1 of the following: 60 years of age or greater, previous MI or CABG, CAD > 50% stenosis in 2 vessels, previous ischemic stroke, diabetes,peripheral arterial disease, or chronic renal dysfunction.

Canadian Journal of Cardiology 29 (2013) 1334-1345


Prasugrel should be avoided in patients with previous TIA or stroke. In patients aged 75 years and older, or body weight <60 kg, prasugrel should be used with caution and a 5-mg dose considered


Prasugrel should be avoided in patients with previous TIA or stroke. In patients aged 75 years and older, or body weight <60 kg, prasugrel should be used with caution and a 5-mg dose considered


Antiplatelet Therapy Post-CABG

? Single-antiplatelet therapy (SAPT)

? Dual-antiplatelet therapy (DAPT)

Management of SCAD patientsAngina relief Event prevention

• β-blockers and/or CCB

Ivabradine Long-acting nitrates Nicorandil Ranolazine Trimetazidine

• Lifestyle management• Control of risk factors

• Aspirin (if intolerance, consider clopidogrel)

• Statins• Consider ACE inhibitors or ARBs

Consider coronary angio → PCI or CABG

Short-acting nitrates, plus

1st line

2nd line

2013 ESC guidelines on the management of stable coronary artery disease.

SCAD

Medical Elective PCIElective CABG

Single-antiplatelet therapy (SAPT) Dual-antiplatelet therapy (DAPT)

Aspirin (Indefinite Therapy)If aspirin intolerant :

Clopidogrel (Indefinite Therapy)

Aspirin plus Clopidogrel BMS : 1 month DES : 6-12 months

The Balance between Anti-ischemic Efficacy and Bleeding Risk of Antithrombotic Therapy

in PC I

Thus, the thousand dollar question is : Where is the sweet spot between ischaemia and bleeding?

What is the optimal duration of DAPT

after PCI?

Randomized controlled trials investigating less than 12 months of DAPT did not show significant differences in their composite endpointscompared with 12 months or prolonged DAPT.

European Heart Journal (2015) 36, 1207–1211

Rates of bleeding are consistently higher for prolonged DAPT, reaching statistical significance in some studies


The appropriate duration of DAPT for patients following placement of a DES remains controversial.

The “Will this trial change my practice?” sessions at PCR 2015

Will this trial change my practice? The Dual Antiplatelet Therapy (DAPT) study – 12 or 30 months of dual

antiplatelet therapy after drug-eluting stents

Should the DAPT study shift the standard of care from 12 months to 30 months in patients who receive a DES?

Does the increased risk of bleeding essentially offset the benefits?

To whom would you recommend continued DAPT? In whom would you avoid it?

A call for individualised medicine(precision medicine or personalized medicine)

How long should DAPT be continued ? 3, 6, 12, 24, 30 months

The therapeutic sweet spot between reduced ischaemia and increased bleeding markedly differs between patients.

Pharmacogenomics : Determining the right drug in the right dosage at the right time for

each and every patient

Pers

onal

ized

Trea

tmen

t:

Dre

am o

r Rea

lity?

Thromb Haemost 2015; 113: 37–52

Pharmacogenomics

Ischemic RiskBleeding Risk

Balanced Benefit/Risk Ratio

Tailoring antiplatelet therapy : a step toward individualized therapy to improve clinical outcome?

Proposed duration of dual antiplatelet therapy after DES (based on individual risk)


Long-term risk factors for stent thrombosis after PCI

Pharmacological factors

Patientcharacteristics

Proceduralfactors

-Premature discontinuationof DAPT

-Slow metabolizers of the antiplatelet

pro-drug

-Diabetes-ACS

-LV dysfunction-Malignancy

-Stent type-Stent undersizing-Incomplete stent

expansion-Incomplete apposition

-Greater stent length-Side branch stenting

-Overlapping stents-Small vessel calibre


Pharmacologicalfactors

Patientcharacteristics

Proceduralfactors

-Prolonged DAPT-Concomitant use

of OAC

-Age-History of bleeding

-Low body weight-ACS

-Thrombocytopenia-GI disease

-Impaired kidney function-Liver disease

-Cerebrovascular accident-Malignancy

Short-term riskfactors:

-Femoral access,-Large sheath size

-No vascularclosure device

Long-term riskfactors:

-Unknown

Long-term risk factors for bleeding after PCI


Factors for physicians to consider in determining the optimal duration of DAPT after DES implantation for individual patients

Eisen, A. & Bhatt, D. L. (2015) Defining the optimal duration of DAPT after PCI with DES Nat. Rev. Cardiol. doi:10.1038/nrcardio.2015.87

Triple Antithrombotic TherapyDual-antiplatelet therapy (DAPT) + Oral AntiCoagulant (OAC )

Oral AntiCoagulants (OACs)

Vitamin K Antagonist(VKA )Warfarin

Factor IIaDabigatran

Factor XaRivaroxaban

Apixaban

Non-VKA oral anticoagulants (NOACs), previously referred to as new or novel OACs

Triple Antithrombotic TherapyRisky but sometimes necessary

Dual-antiplatelet therapy (DAPT):Oral AntiCoagulant (OAC):

Continuing DAPT + OAC

Bleeding risk

Discontinuing OAC

Stroke risk

Discontinuing DAPT

Stent thrombosis

risk

Triple Antithrombotic Therapyin AF patients with ACS/PCI

Issues for Mr. X

Joint consensus document :European Heart Journal (2014)

Clinical settingElective PCI in stable CAD

ACS (either STEMI or NSTEMI )

Stroke riskCHA2DS2-VASc score

Bleeding riskHAS-BLED score

Antithrombotic therapy Triple(OAC+DAPT) , dual(OAC+SAPT) , mono(OAC)

Antithrombotic management in NVAF patients with ACS/PCI

Non-valvular AF : Stroke risk

Elective PCI in SCAD

High( CHA2DS2-VASC

≥2 )

Moderate(CHA2DS2-VASC =1

in males ,=2 in women)

Low or moderate (HAS-BLED 0–2)

At least 4 weeks (no longer than 6 months): triple therapy of OAC+

aspirin + clopidogrelUp to 12th month: OAC and clopidogrel (or alternatively,aspirin)Lifelong : OAC

ACSHigh

(CHA2DS2-VASC ≥2)

Moderate(CHA2DS2-VASC =1 in

males,=2 in women)

Low or moderate (HAS-BLED 0–2)

6 months: triple therapy of OAC + aspirin + clopidogrelUp to 12th month: OAC and clopidogrel (or alternatively,aspirin)Lifelong: OAC

OAC and clopidogrel

Elective PCI in SCAD

Moderate (CHA2DS2-VASC =1 in

males,=2 in women)

High (HAS-BLED ≥3)

12 months: OAC and clopidogrel

Lifelong: OAC

ACS Elective PCI in SCAD

High (CHA2DS2-VASC

≥2)

Moderate (CHA2DS2-VASC =1 in males,=in women)

High (CHA2DS2-VASC

≥2)

High (HAS-BLED ≥3)

4 weeks: triple therapy of OAC + aspirin + clopidogrelUp to 12th month: OAC and clopidogrel (or alternatively,aspirin)Lifelong: OAC

OAC and clopidogrel

For PCI, BMS may be considered to minimize duration of DAPT Class IIb C

After coronary revascularization in patients with CHA2DS2-VASc score ≥2, it may be reasonable to use clopidogrel concurrently with oral anticoagulants but without aspirin Class IIb B

The balance of bleeding and ischaemic events in surgical patients after

stenting.

Continuing DAPT

Bleeding risk

Discontinuing DAPT

Stent thrombosis risk

Issues for Mr. X

Surgery in patients on dual antiplatelet therapy

Proposed bridging protocols for patients on dual-antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor referred to cardiac or noncardiac surgery.

Davide Capodanno, and Dominick J. Angiolillo Circulation. 2013;128:2785-2798

Copyright © American Heart Association, Inc. All rights reserved.

Rabeprazole ------------- PARIET

Pantoprazole -----------CONTROLOC

Omeprazole --------------LOSEC

Lansoprazole -----------LANZOR

Esomeprazole ---------NEXIUM

(Circ Cardiovasc Qual Outcomes. 2015)

Light transmission aggregometry (LTA)

Factors linked to clopidogrel response variability. Thromb Haemost 2015; 113: 37–52

A proposed algorithm for personalised antiplatelet treatment with P2Y12

receptor blockers

*The PREDICT score might be

used when ticagrelor or

prasugrel are not available or

contraindicated.

Health & Medicine

Dapt duration