The PLATO ( A Study of Platelet Inhibition and Patient Outcomes ) trial showed that Ticagrelor ( Brilinta ) has reduced the rate of cardiovascular events ( cardiovascular death, myocardial infarction or stroke ) from 11.7% to 9.8% compared Clopidogrel ( Plavix ) ( p<0.001, RRR = 16% ), without an increase in major bleeding. This efficacy endpoint was driven by a statistically significant reduction in both cardiovascular death and myocardial infarction with no difference in stroke.

Ticagrelor is the first antiplatelet agent to demonstrate a reduction in cardiovascular death across all major acute coronary syndromes patient types.

For every 1,000 patients admitted to the hospital because of an acute coronary syndrome, use of Ticagrelor instead of Clopidogrel, for up to one year, led to 14 fewer deaths, or 11 fewer myocardial infarction's, or 8 fewer cases of stent thrombosis, without an increase in major bleeds.
In the PLATO study, the reduction in risk of cardiovascular events appears early and the benefit over clopidogrel grows with time.
Ticagrelor demonstrated a consistent benefit across multiple secondary efficacy endpoints including cardiovascular death and total mortality; myocardial infarction; the composite of myocardial infarction, stroke, and total mortality; and a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack ( TIA ), recurrent cardiac ischemia, severe recurrent cardiac ischemia, and other arterial thrombotic events.

The PLATO study confirmed the clinical safety profile of previous Ticagrelor studies by showing an efficacy advantage without an increase in major bleeding. Across all the important patient subgroups ( e.g. gender, weight, history of stroke/TIA ) in PLATO, Ticagrelor showed no difference versus Clopidogrel in the incidence of major bleeding. When minor bleeding was added, Ticagelor showed a small increase in PLATO defined major plus minor bleeding versus Clopidogrel.
At continuous ECG monitoring wile in hospital, but not at later follow-up in the outpatient setting, pauses in the heart rhythm were seen more frequent with Ticagrelor. However such pauses were not associated with any symptoms or clinical consequences for the patient. Transient symptoms of dyspnoea were reported more often by patients on Ticarelor but only one in 100 Ticagrelor treated patients overall stopped taking study medication due to dyspnoea.

PLATO was a head-to-head outcomes study of Ticagrelor plus Acetylsalicylic Acid ( Aspirin ) versus the active comparator, Clopidogrel plus Acetylsalicylic Acid, and was designed to establish whether Ticagrelor could achieve meaningful cardiovascular endpoints in acute coronary syndrome patients. 18,624 patients at 893 sites in 43 countries across all continents were successfully recruited. All patients were admitted to hospital because of acute coronary syndrome, one third with ST-elevation myocardial infarction and two thrirds without ST-elevation. Shortly after admission to hospital, the patients started their long-term anti-platelet treatment with either Ticagrelor ( 90 mg twice daily ) or Clopidogrel ( 75 mg daily ) in a randomized, double-blind fashion for 6-12 months.

Ticagrelor is the first reversibly binding oral adenosine diphosphate ( ADP ) receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP. ADP receptor blockade inhibits the action of platelets in the blood, reducing recurrent thrombotic events. Ticagrelor is the first in a new chemical class, the CPTPs ( cyclopentyl-triazolo-pyrimidines ) and is chemically distinct from the thienopyridines, such as Clopidogrel and Prasugrel ( Efient ).

Source: European Society of Cardiology, 2009

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