Antiplatelet therapy-Before, during and after hospitalization for ACS

Dr Akshay MehtaAsian Heart Institute

Nanavati Superspeciality Hospital

A 62 year old gentleman develops typical chest pain at home. What drug(s) should he take on

the way to the hospital ?

• Chewable aspirin 325 mg• Enteric coated aspirin 325 mg• Chewable aspirin 75 mg with ticagrelor 180 mg• Chewable aspirin 325 mg with clopidogrel 300 mg

If it turns out to be a case of NSTE-ACS in the hospital with ST changes and raised Troponins. when & which P2Y12 inhibitor you will advise?

A. On diagnosis, 300 mg clopidogrelB. In cath lab, before PCI 600 mg clopidogrelC. On diagnosis, 60 mg prasugrelD. On diagnosis, 180 mg ticagrelorE. In cath lab, before PCI 180 mg ticagrelor

In the TRILOGY ACS trial, comparing prasugrel with clopidogrel, prasugrel _____ the incidence of the primary efficacy endpoint (composite of cardiovascular death, MI, or stroke) in patients age < 75 years.

• Significantly increased• Significantly decreased• Had no significant effect on

Answer: Had no significant effect onIn the TRILOGY ACS trial, patients with ACS were eligible if they were selected for a final treatment strategy of medical management without revascularization within 10 days of the index event. Patients were randomized to receive either prasugrel or clopidogrel. The primary efficacy endpoint was a composite of cardiovascular death, MI, or stroke among patients under the age of 75 years. Patients were evaluated up to 30 months. At 30 months, there was no significant between-group difference in the rate of the primary efficacy endpoint; the primary endpoint occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (HR 0.91; 95% CI 0.79-1.05; P = .21). Prasugrel is not recommended in clinical practice guidelines in patients managed without PCI (ie, not recommended in patients managed conservatively/medically).

Clopidogrel No

Trial Pretreatment Pretreatment

PCI-CURE 3.6 5.1

CREDO n/a n/a

PCI-CLARITY 4.0 6.1

Overall 3.7 5.5

Clopidogrel NoTrial Pretreatment PretreatmentPCI-CURE 2.9 4.4CREDO 6.0 7.1PCI-CLARITY 3.3 5.4Overall 3.9 5.5

Meta-Analysis of Clopidogrel Pretreatment

1.00.25 2.00.5

1.00.25 2.00.5OR (95% CI)

OR (95% CI)

CV Death or MI after PCI (%)

MI before PCI (%)

OR 0.67P=0.005

FavorsPretreatment

FavorsNo Pretreatment

OR 0.71P=0.004

Sabatine MS et al. JAMA 2005;294:1224-32

PLATO study design

Primary endpoint: CV death + MI + Stroke Primary safety endpint: Total major bleeding

6–12-month exposure

ClopidogrelIf pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,

then 75 mg qd maintenance;(additional 300 mg allowed pre PCI)

Ticagrelor180 mg loading dose, then

90 mg bid maintenance;(additional 90 mg pre-PCI)

NSTE-ACS (moderate-to-high risk) STEMI (if primary PCI)Clopidogrel-treated or -naive;

randomised within 24 hours of index event (N=18,624)

PCI = percutaneous coronary intervention; ASA = acetylsalicylic acid; CV = cardiovascular; TIA = transient ischaemic attack

Conclusions• Reversible, more intense P2Y12 receptor inhibition for one year with

ticagrelor in comparison with clopidogrel in a broad population with ST- and non-ST-elevation ACS provides

– Reduction in myocardial infarction and stent thrombosis

– Reduction in cardiovascular and total mortality

– No change in the overall risk of major bleeding

Ticagrelor is a more effective alternative than clopidogrel for the continuous prevention of ischaemic events, stent

thrombosis and death in the acute and long-term treatment of patients with ACS

Recommendations for platelet inhibition in non-ST elevation ACS

-2015 ESC guidelines on UA/NSTEMI

• Aspirin for all without contraindications • Ticagrelor (180 mg loading dose, then 90 mg twice daily) in the

absence of contraindications regardless of initial treatment strategy for all patients at moderate-to-high risk of ischaemic events (e.g. elevated cardiac troponins),and including those pretreated with clopidogrel

• Prasugrel (60 mg loading dose, 10 mg daily dose) is recommended ONLY in patients who are proceeding to PCI if no contraindication

• Clopidogrel (300–600 mg loading dose, 75 mg daily dose) is recommended for patients who cannot receive ticagrelor or prasugrel or who require oral anticoagulation.

A 74 years age man enters ER with chest pain of 2 hours’ duration. ECG shows acute anterior wall STEMI. He is a diabetic without h/o stroke, bleed or TIA in past. Family has yet to decide about primary PCI. What antiplatelet besides aspirin will you advise the ER to give & at what

dosage ?

• Clopidogrel 300 mg• Ticagrelor 180 mg• Prasugrel 60 mg• Clopidogrel 600 mg

Adjunctive Antithrombotic Therapy to Support Reperfusion With Fibrinolytic Therapy

2013 ACCF/AHA STEMI guidelines

After taking 300 mg of clopidogrel, he opts for PCI. What additional

antiplatelet drug will you advise ?

• 300mg more of clopidogrel• 180 mg of ticagrelor • 60 mg of prasugrel• Nothing

An 78 year old gentleman opts for fibrinolysis for an acute MI.

Besides aspirin, the other antiplatelet drug advisable before lytic therapy is :

• Clopidogrel loading dose of 300 mg• Clopidogrel 75 mg• Ticagrelor half loading dose of 90 mg• Prasugrel half loading dose of 30 mg

It is beneficial to give Ticagrelor, pre hospital in ambulance in a case of acute STEMI and decided to be taken up for primary PCI.

• True

• False

Definite Stent Thrombosis up to 30 Days after Ticagrelor Administration in the Modified Intention-to-Treat Population.

Montalescot G et al. N Engl J Med 2014;371:1016-1027.

In the TRITON-TIMI 38 trial, a post-hoc analysis revealed that favorable net clinical benefit was observed with prasugrel versus clopidogrel only in:

A. Patients with and without prior stroke/TIAB. Patients without prior stroke/TIAC. Patients weighing < 60 kgD. Patients age ≥ 75 yearsE. Patients without prior stroke/TIA, weight ≥ 60 kg and age ≤75 years

Answer: Patients without prior stroke/TIAIn the TRITON-TIMI 38 trial, a series of post-hoc exploratory analyses were performed to identify the subgroups of patients who did not have a favorable net clinical benefit (defined as the rate of death from any cause, nonfatal MI, nonfatal stroke, or non-CABG-related nonfatal TIMI major bleeding) from the use of prasugrel or who had net harm. Patients who had a previous stroke or TIA had net harm from prasugrel (HR 1.54, 95% CI 1.02-2.32). Therefore, the prescribing information for prasugrel indicates that prasugrel should not be used in patients with a history of TIA or stroke. Patients 75 years of age or older had no net benefit from prasugrel (HR 0.99, 95% CI 0.81-1.21), and patients weighing less than 60 kg had no net benefit from prasugrel (HR 1.03, 95% CI 0.69-1.53). Patients without prior stroke/TIA, < 75 years, and weighing ≥ 60 kg had a favorable net clinical benefit from the use of prasugrel versus clopidogrel.

A patient of ACS has undergone angiography and has to undergo CABG. Which DAPT combination would have

been the best for him ?

A. Clopidogrel with aspirinB. Prasugrel with aspirinC. Ticagrelor with aspirin

A patient of ACS on DAPT has to undergo elective CABG. Assuming different DAPT combinations going on, when to stop which drug before the surgery ?

A. Stop aspirin and clopidogrel (3 days before)

B. Stop Ticagrelor alone (7 days before) & ct aspirin

C. Stop Clopidogrel alone (5 days before) & ct aspirin

D. Stop Prasugrel alone (5 days before) & ct aspirin

Antiplatelets at time of CABG:2014 ACC/AHA UA/NSTEMI

• Initiate and continue ASA• Discontinue clopidogrel/ticagrelor 5 days before, and prasugrel 7 days before ELECTIVE CABG• Discontinue clopidogrel/ticagrelor Upto 24 hrs before urgent

CABG.• May perform urgent CABG<5 days after discontinuing

clopidogrel/ticagrelor, and < 7 days after discontinuing prasugrel

• Discontinue eptifibatide/tirofiban at least 2-4 hrs before, and abciximab ≥ 12 hrs before CABG

ESC/EACTS 2014

Which dose of aspirin is better for long term use ?

• 75 to 150 mg

• 150 to 325 mg

• 325 mg

High- vs. low-dose aspirin comparison at long-term follow-up.

Sanjit S. Jolly et al. Eur Heart J 2009;30:900-907

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Your 40 year old patient with diabetes undergoes stenting of a large, very proximal LAD for STEMI and is on aspirin & prasugrel. How long will you continue them after PCI ?

A. Aspirin lifelong and prasugrel for 3 months followed by clopidogrel for 9 more months

B. Both aspirin and prasugrel for 1 year and then stop both

C. Aspirin lifelong and prasugrel for 12 months ± clopidogrel long term

D. Both aspirin and prasugrel life long

2014 ESC/EACTS Revasc Guidelines Post PCI

• STEMI/ NSTEMI : Any P2Y12 inhibitor is recommended in addition to ASA, and maintained over 12 months unless there are contraindications such as excessive risk of bleeding. (Class 1)

• • SCAD : DAPT (with clopidogrel) is indicated for at least 1 month

after BMS implantation and for 6 months after DES implantation. (both class 1)

• Shorter DAPT duration (<6 months) may be considered after DES implantation in patients at high bleeding risk. (Class Iib)

In the DAPT study, dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin alone, resulted in _______ in the composite of major adverse cardiovascular and cerebrovascular events and ____ in the risk of moderate or severe bleeding.

A. No difference, no differenceB. A decrease, no differenceC. No difference, an increaseD. A decrease, an increaseE. A decrease, a decrease

Answer: A decrease, an increaseIn the DAPT study, the primary analysis cohort was randomized drug-eluting stent-treated subjects. Continued treatment with dual antiplatelet therapy (aspirin plus a thienopyridine in the DAPT study) for beyond 12 months reduced the rate of major cardiovascular and cerebrovascular events (4.3% vs 5.9% with only 12 months of dual therapy treatment; HR 0.71, 95% CI 0.59-0.85, P < .001). However, longer duration of thienopyridine therapy was associated with a significant increase in moderate or severe bleeding (2.5% vs 1.6%, P = .001).

A 62 years age male patient of stable angina on 75 mg daily aspirin only, gets admitted for PTCA. When, which and what dose of antiplatelet drugs would you

advise to be taken ?

A. Clopidogrel 600 mg 2 hours before PTCA

B. Clopidogrel 300 mg 1 hour before PTCA

C. Prasugreal 60 mg just before PTCA

D. Ticagrelor 180 mg 2 hours before PTCA

2014 ESC/EACTS Guidelines on myocardialrevascularization- antiplatelets during stenting

for Stable CAD

• ASA is indicated before elective stenting. (I B) • ASA oral loading dose of 150–300 mg (or 80-150 mg

i.v.) is recommended if not pre-treated. (I C)• Clopidogrel (600 mg loading dose or more, 75 mg

daily maintenance dose) is recommended for elective stenting. (1A)

• GP IIb/IIIa antagonists should be considered only for bail-out.(IIaC)

A pt on OAC for AF undergoes PTCA. What antiplatelet therapy would you recommend for him ?

• OAC +Aspirin + Clopidogrel for 12 months• OAC +Aspirin + Clopidogrel for 1 month,

followed by OAC +Aspirin till 12 months• OAC + Ticagrelor for 12 months• Depends on clinical situation, bleeding risk,

clotting risk

Recommendations for antithrombotic treatment in patients undergoing PCI who require oral

anticoagulation ESC/EACTS 2014

DAPT in pt with OAC for AF

One way to ensure faster action of P2Y12 inhibitors is :

A. Administer clopidogrel by rectal suppository

B. Give prasugrel in liquid form

C. Crush ticagrelor and swallow with water

Aspirin + Clopidogrel v/s Ticagrelor v/s Prasugrel

• Chest pain

• ACS A Non ACS

UA/NSTEMI T C STEMI C (PCI or conservative)

Pr PCI T C Fibrinolysis C Prasugrel- only at time of PCI in any ACS

Take Home……

• Aspirin for all, forever

• Only clopidogrel for fibrinolysis

• Ticagrelor , at diagnosis, preferred for all moderate to high risk NSTE-ACS even if preloaded with clopidogrel

• Prasugrel - only before PCI, esp diabetics, STEMI –remember contraindications

……….Take Home

• Ticagrelor beneficial if given prehospital in STEMI • In elective CABG, continue low dose aspirin and stop

clopidogrel, ticagrelor 5 days before and prasugrel 7 days before Sx

• In urgent surgery, continue continue low dose aspirin and stop clopidogrel, ticagrelor, prasugrel 1 day before . Weigh bleeding v/s thrombosis risk.

• Post CABG, continue aspirin lifelong, clopidogrel for at least a month, esp for off pump surgery in pts with low bleeding risk