PEGASUS-TIMI 54 study data reinforce the need for long-term secondary prevention of cardiovascular events

AstraZeneca has announced details of a sub-analysis of the PEGASUS-TIMI 54 study, assessing the effect of Brilique™ (ticagrelor) in reducing atherothrombotic events in post-heart attack patients, based on the time from withdrawal of their previous P2Y12 inhibitor antiplatelet therapy. Current European guidelines recommend that dual antiplatelet therapy is stopped 12 months after a heart attack. The PEGASUS-TIMI 54 study enrolled patients who had suffered a heart attack one to three years previously.

The data, presented during a Clinical Trial Update hotline session at the European Society of Cardiology (ESC) Congress 2015, demonstrated that withdrawal from P2Y12 inhibitor antiplatelet therapy is associated with heightened risk of ischaemic events, including cardiovascular death, myocardial infarction or stroke.

Patients enrolled into the placebo arm of the PEGASUS-TIMI 54 study who had recently discontinued previous P2Y12 inhibitor antiplatelet therapy (within 30 days) were at heightened risk of developing a subsequent ischaemic event, compared to those who had stopped therapy over 30 days previously, regardless of the time since their original heart attack. This may be due to differences in baseline characteristics (although adjusted for in this analysis) as well as exposing continued risk by the withdrawal of therapy.

Those patients randomised into the ticagrelor arms of the study within 30 days of withdrawal of therapy experienced a 27% reduction in the risk of developing a subsequent event. The benefit of treatment with ticagrelor had the greatest effect in this group, with the effect on risk decreasing as the length of time from last dose increased [≤30 days HR 0.73, >30 days to 360 days HR 0.86, >360 days HR 1.01].

Dr. Marc P. Bonaca, MD, MPH, lead investigator for the sub-analysis study, Associate Physician in Cardiovascular Medicine at Brigham and Women's Hospital and an investigator at the TIMI Study Group, said: "These findings suggest greater benefit in continuing P2Y12 inhibition beyond 12 months therapy without interruption than in re-initiating such therapy in patients who have remained stable for more than 2 years after their MI and more than 1 year off of a P2Y12 inhibitor."

Marc Ditmarsch, Global Development Lead for Brilique said: "We welcome the results of this sub-analysis, which furthers our understanding of the underlying cardiovascular risk for patients who have suffered a heart attack in the past. It also provides further insight into which patients could potentially benefit most from longer term treatment with ticagrelor."

The PEGASUS-TIMI 54 study investigated the efficacy and safety of ticagrelor at both 60mg and 90mg twice daily, plus low dose aspirin, compared to placebo plus low dose aspirin, for the long-term prevention of atherothrombotic events in patients who had suffered a heart attack one to three years prior to study enrollment. The key findings of the main study were:

• Both 90mg and 60mg study doses of ticagrelor with aspirin significantly reduced the primary composite endpoint of cardiovascular (CV) death, myocardial infarction (MI) or stroke compared to placebo.
• As expected with an oral antiplatelet and consistent with studies in similar patient populations, TIMI Major Bleeding*, the study's primary safety endpoint, was higher with both doses of ticagrelor plus aspirin compared to placebo plus aspirin. Importantly, the rates of intracranial haemorrhage (bleeding in the skull) and fatal bleeding were low and were similar between study groups and the placebo arm.

The full results of the PEGASUS-TIMI 54 study were published in the New England Journal of Medicine¹ in March 2015.

Ticagrelor, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndromes including patients managed medically, and those who are managed with percutaneous coronary intervention (PCI) or coronary artery by-pass grafting (CABG).² Ticagrelor is currently recommended for treatment for up to 12 months and is now under regulatory authority review in the EU and the U.S. for use in the chronic secondary prevention of atherothrombotic events in patients who had experienced a heart attack within one to three years.