June 9, 2015 - AstraZeneca announced full results from the PEGASUS-TIMI 54 study, a large-scale outcomes trial investigating Brilinta (ticagrelor) tablets plus low dose aspirin, at the American College of Cardiology (ACC) 64 th annual scientific session and expo in March. The study compared Brilinta to placebo plus low dose aspirin, for the chronic secondary prevention of atherothrombotic events in patients who had experienced a heart attack one to three years prior to study enrolment. Study results were simultaneously published in the New England Journal of Medicine online.
Key findings included:
- 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; and
- 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 within the skull) and fatal bleeding were low and were similar between study groups and the placebo arm.
Recent research has shown that one in five patients will have a further heart attack, stroke or CV death in the subsequent three years following a heart attack, even if patients were event free after 12 months. For patients more than one year on from a heart attack, the current standard of care is aspirin alone. The PEGASUS-TIMI 54 study was designed to investigate the effect of adding ticagrelor at 60mg and 90mg to low dose aspirin on reducing the risk of CV death, heart attack or stroke in patients aged 50 and older with a history of heart attack and one additional CV risk factor.
In this trial, both study doses of ticagrelor significantly reduced the primary endpoint of CV death, MI or stroke compared to placebo. The rates at three years were 7.85 percent in the ticagrelor 90mg arm, 7.77 percent in the ticagrelor 60mg arm, and 9.04 percent in the placebo arm (Hazard Ratio (HR) for ticagrelor 90mg vs placebo 0.85, 95 percent CI 0.75 – 0.96, P=0.0080; HR for ticagrelor 60mg vs placebo 0.84, 95 percent CI 0.74 – 0.95, P=0.0043).
The effect of ticagrelor on each of the components of the primary endpoint was consistent. A numerical decrease in the secondary endpoints of cardiovascular death and all-cause mortality was observed, but did not reach statistical significance.
In addition, the primary efficacy endpoint of both doses of ticagrelor appeared consistent across major subgroups including age, sex, index MI type (STEMI/NSTEMI), time from qualifying MI, diabetes, aspirin dose, history of percutaneous intervention (angioplasty) and geographical region.
As expected, TIMI Major bleeding was higher with both doses of ticagrelor compared to placebo, with rates at three years of 2.60 percent in the ticagrelor 90mg arm, 2.30 percent in the ticagrelor 60mg arm, and 1.06 percent in the placebo arm (HR for ticagrelor 90mg vs placebo 2.69, 95 percent CI 1.96 – 3.70, p<0.001; HR for ticagrelor 60mg vs placebo 2.32, 95 percent CI 1.68 – 3.21, p<0.001).
However, the rates of fatal bleeding or intracranial haemorrhage were low and similar between treatment arms.
Fatal bleeding rates at three years were 0.11 percent in the ticagrelor 90mg arm, 0.25 percent in the ticagrelor 60mg arm, and 0.26 percent in the placebo arm (HR for ticagrelor 90mg vs placebo 0.58, 95 percent CI 0.22 – 1.54, p=0.27; HR for ticagrelor 60mg vs placebo 1.00, 95 percent CI 0.44 – 2.27, p=1.00).
Intracranial hemorrhage rates at three years were 0.56 percent in the ticagrelor 90mg arm, 0.61 percent in the ticagrelor 60mg arm, and 0.47 percent in the placebo arm (HR for ticagrelor 90mg vs placebo 1.44, 95 percent CI 0.83 – 2.49, p=0.19; HR for ticagrelor 60mg vs placebo 1.33, 95 percent CI 0.77 – 2.31, p=0.31).
The PEGASUS-TIMI 54 study, part of the PARTHENON program, involved more than 21,000 patients from over 1,100 sites in 31 countries.
For more information: www.astrazeneca.com