1.1. Disease prevalence and incidence

Myocardial infarction (MI) is usually caused by blockage of a coronary artery that results in myocardial tissue death.¹ The rupture or fissuring of an unstable atherosclerotic plaque is often the precipitating factor that leads to platelet activation and aggregation, and subsequent thrombus formation.⁹

In 2014 to 2015, there were 69,762 in-patient hospitalizations for acute MI in Canada.² Although mortality rates have been declining, MI is associated with significant morbidity and mortality.³ Patients report having to take medication multiple times a day, frequent visits to a health care provider, taking time off work, and limitations to their activities following their MI.

1.2. Standards of therapy

Patients with MI have heightened platelet activation and aggregation and are at increased risk of recurrent ischemic events.⁹ Canadian and US guidelines recommend dual antiplatelet therapy, with ASA plus either clopidogrel, ticagrelor, or prasugrel, for up to the first 12 months following an acute MI.^1,3,10,11 After the first year, ASA is the standard of care for the long-term secondary prevention of atherothrombotic events. Clopidogrel monotherapy is also indicated for long-term secondary prevention in patients with prior MI and may be used in place of acetylsalicylic acid (ASA) in some patients (Table 2).^11,12

Table 2

Key Characteristics of Platelet Aggregation Inhibitors.

1.3. Drug

Ticagrelor is an oral, direct-acting, selective and reversibly binding P2Y₁₂ receptor antagonist that prevents adenosine diphosphate (ADP)-mediated P2Y₁₂-dependent platelet activation and aggregation.⁴ The new indication for ticagrelor is as follows: co-administered with low-dose (75 mg to 150 mg) acetylsalicylic acid (ASA), for the prevention of atherothrombotic events in adult patients with a history of MI (occurred at least one year ago) and a high risk of developing an atherothrombotic event. The recommended dose is 60 mg twice daily, orally. Health Canada has specified that no loading dose is required, and the 90 mg dose should not be used for this indication. Health Canada has also specified that treatment can be initiated up to two years from the spontaneous myocardial infarction, or within one year after stopping previous ADP receptor antagonist treatment, and that treatment duration is not to exceed three years of extended treatment.

Ticagrelor is also approved for the secondary prevention of atherothrombotic events (in combination with ASA) in patients with acute coronary syndromes (unstable angina, non–ST elevation MI, or ST elevation MI) who are to be managed medically and those who are to be managed with percutaneous coronary intervention (PCI) (with or without stent) and/or coronary artery bypass graft (CABG). The CADTH Canadian Drug Expert Committee (CDEC) recommended that ticagrelor not be listed at the submitted price for the following reasons:

• The pre-specified subgroup analysis (by region), in the one large randomized controlled trial (RCT) of patients with acute coronary syndrome, did not provide evidence of the superiority of ticagrelor compared with clopidogrel in a North American patient population to support a higher price for ticagrelor.
• Given the limitations identified with the manufacturer’s pharmacoeconomic submission, CDEC noted that the cost-effectiveness of ticagrelor could not be properly assessed.
• The daily cost of ticagrelor ($2.96) is greater than clopidogrel ($2.58).⁵