CAN NEWER ANTIPLATELETS REPLACE CLOPIDOGREL ?

Dr. Arindam Pande MD, DMAssociate Consultant, CardiologyApollo Gleneagles Hospital, Kolkata

WHAT ABOUT…?

Stable IHD managed conservatively / post-CABG patients intolerant or sensitive to aspirin

ACS patients managed conservatively

-- Clopidogrel is the only choice

PRIMARY PCI..

Indication / advantage of primary PCI (even in the initial 3 hours of chest pain), when thrombolysis is contraindicated e.g. - -History of stroke or transient ischemic attack,

-Active pathological bleeding,

-Patients aged ≥75 years

-- Prasugrel can not be used

LOADING DOSE OF CLOPIDOGREL..

TRITON TIMI 38 – all patients in clopidogrel arm received 300 mg loading dose

PLATO – majority of patients in clopidogrel arm received 300 mg loading dose

-- ACC/AHA recommend 600 mg loading dose of clopidogrel prior to PCI (suuported by multiple RCTs e.g. ARMYDA-2, ALBION etc.)

TICAGRELOR..

BID dosing Dyspnea in 13% treated patients Ventricular pause Increased creatinine and uric acid levels No benefit of ticagrelor (indeed harm) in US /

Canada patients – unclear reason (PLATO) Higher bleeding

PRASUGREL.. Caution in patients < 60 kg body weight Not be started in patients likely to undergo

urgent CABG Should be discontinued for longer period (at

least 7 days) prior to any surgery Increased cancer cases reported in prasugrel

arm (TRITON TIMI 38) Early benefit but increasing risk of bleeding

with prolonged use may offset later benefits

CANGRELOR - Only IV formulation available,

shown benefit

-- during periprocedural period of PCI followed by clopidogrel maintenance (CHAMPION PHOENIX Study)

--as bridge therapy during CABG (BRIDGE Study)

ELINOGREL - No difference in clinical efficacy as compare to clopidogrel (INNOVATE PCI Trial)

VORAPAXAR - In NSTE ACS patients (TRACER Trial)

--did not significantly reduce the composite of CV death, MI, stroke, hospitalization for ischemia, or urgent revascularization

--along with significantly increased bleeding

Clopidogrel and PPI Omeprazole decreases pharmacodynamic effect of

clopidogrel (common CYP metabolism) but no effect on clinical outcome (PRINCILPE TIMI-44,TRITON TIMI-38 TRIAL).

No difference in primary composite cardiovascular endpoint with reduced GI bleeding (COGENT TRIAL).

Health care providers avoid prescribing omeprazole, esomeprazole, or cimetidine to patients receiving clopidogrel.

Use one of the other PPIs (e.g., pantoprazole, rabeprazole) and separate the PPI and clopidogrel by around 14-18 hrs by prescribing the PPI before breakfast and clopidogrel at bedtime

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)P=0.0004

Prasugrel

Clopidogrel

Days

En

dp

oin

t (%

)

12.1

9.9

HR 1.32(1.03-1.68)P=0.03

Prasugrel

Clopidogrel1.8

2.4

138 ↓ events

35 ↑ events

TRITON-TIMI 38 study Balance of Efficacy and Safety

CV Death / MI / Stroke

TIMI Major NonCABG Bleeds

NNT = 46

NNH = 167

Thank you..