A Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multinational Trial, to Assess the Prevention of Thrombotic Events with Ticagrelor Compared to Placebo on a Background of Acetyl Salicylic Acid (ASA) Therapy in Patients with History of Myocardial Infarction

Atherothrombosis is associated with the main causes of mortality on a worldwide
scale. Its prevalence will further increase in the future. Moreover, after the
initial manifestation of atherothrombosis, patients remain at high risk for
serious complications for years after their initial event. It has been proven
that dual-antiplatelet therapy is beneficial compared to treatment with ASA
alone for patients with acute coronary syndrome (ACS) for up to a year of
therapy. Ticagrelor is a reversible, potent, oral platelet aggregation
inhibitor, which works through inhibition of the adenosine diphosphate (ADP)
P2Y12 receptor. In the phase III PLATO trial, patients presenting with an acute
coronary syndrome were randomized to ticagrelor (180 mg loading dose followed
by 90 mg twice daily) or clopidogrel (300-600 mg loading dose followed by 75 mg
daily) for up to 12 months. The trial demonstrated the superiority of
ticagrelor in the prevention of both fatal and non-fatal cardiovascular events
with no significant increase in major bleeding. Currently, there are no data to
support dual therapy beyond 12 months. However, post hoc analysis suggests that
dual antiplatelet therapy would likely provide clinical benefit for high risk
population with prior myocardial infarction. .

The current study is being conducted to determine whether long-term
dual-antiplatelet therapy with ticagrelor in combination with ASA (recommended
daily dose 75-100 mg) is beneficial in patients with history of MI (1-3 years
ago) and additional risk factors for atherothrombosis compared with monotherapy
with ASA alone.

A Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase III
Trial.

Patients will be randomised to 90 mg or 60 mg of ticagrelor orally bd or
placebo for a minimum treatment duration of 12 months.

The patient is asked to visit the hospital for at least 6 times and maximum 11
times. Blood samples will be taken in this study. The total volume of blood
that will be collected is 81 ml. The patient will be asked to fill out a short
questionnaire on his/her quality of life at maximum 5 visits. The patient will
undergo a physical examination at 2 visits. The patient will have an
electrocardiogram at 2 visits. Woman of child-bearing potential have to provide
a urine sample to test for pregnancy.

The study medication may cause some side effects. The taking of a blood sample
may cause some discomfort and there is the possibility of bruising.