Study shows Brilinta treatment reduced thrombotic cardiovascular events in patients with a history of heart attack

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AstraZeneca has announced full results from the PEGASUS-TIMI 54 study, a large-scale outcomes trial that investigated Brilinta (ticagrelor) tablets plus low dose aspirin, compared to placebo plus low dose aspirin, for chronic secondary prevention of atherothrombotic events in patients who had experienced a heart attack one to three years prior to study enrolment.

Both study doses of ticagrelor significantly reduced the primary endpoint of cardiovascular death, myocardial infarction or stroke compared to placebo. The rates at three years were 7.85% in the ticagrelor 90mg arm, 7.77% in the ticagrelor 60mg arm, and 9.04% in the placebo arm (hazard ratio for ticagrelor 90mg vs placebo 0.85, 95% CI 0.75 – 0.96, p=0.0080; hazard ratio for ticagrelor 60mg vs placebo 0.84, 95% confidence interval 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 myocardial infarction type (STEMI/NSTEMI), time from qualifying myocardial infarction, diabetes, aspirin dose, history of percutaneous intervention (angioplasty), and geographical region.

As expected, thrombolysis in myocardial infarction major bleeding was higher with both doses of ticagrelor compared to placebo, with rates at three years of 2.60% in the ticagrelor 90mg arm, 2.30% in the ticagrelor 60mg arm, and 1.06% in the placebo arm (hazard ratio for ticagrelor 90mg vs placebo 2.69, 95% confidence interval 1.96–3.70, p<0.001; hazard ratio for ticagrelor 60mg vs placebo 2.32, 95% confidence interval 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 3 years were 0.11% in the ticagrelor 90mg arm, 0.25% in the ticagrelor 60mg arm, and 0.26% in the placebo arm (hazard ratio for ticagrelor 90mg vs placebo 0.58, 95% confidence interval 0.22–1.54, p=0.27; HR for ticagrelor 60mg vs placebo 1.00, 95% confidence interval 0.44–2.27, p=1.00).

Intracranial haemorrhage rates at three years were 0.56% in the ticagrelor 90mg arm, 0.61% in the ticagrelor 60mg arm, and 0.47% in the placebo arm (hazard ratio for ticagrelor 90mg vs placebo 1.44, 95% confidence interval 0.83–2.49, p=0.19; hazard ratio for ticagrelor 60mg vs placebo 1.33, 95% confidence interval 0.77–2.31, p=0.31).

The data were presented during the opening late-breaking clinical trial session of the American College of Cardiology’s 64th Annual Scientific Session (14–16 March, San Diego, USA), and also simultaneously published in the New England Journal of Medicine online.

Recent research has shown that one in five patients will have a further heart attack, stroke or cardiovascular 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 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 60mg or 90mg twice daily to low dose aspirin on reducing the risk of cardiovascular death, heart attack or stroke in patients aged 50 and older with a history of heart attack and one additional cardiovascular risk factor.

The study is part of the PARTHENON programme. The PLATO study, involving over 18,000 patients, was the first study in the programme and is the basis on which ticagrelor has been approved in over 100 countries and included in 12 major acute coronary syndrome treatment guidelines globally. Further ongoing PARTHENON studies are assessing ticagrelor for the prevention of cardiovascular events in patients with peripheral arterial disease, ischaemic stroke or transient ischaemic attack, and in patients with diabetes and coronary atherosclerosis.

Ticagrelor is not approved for secondary prevention of atherothrombotic events in patients with a history of heart attack beyond one year. Brilinta is not approved for secondary prevention of atherothrombotic events in patients with a history of heart attack beyond one year or for the prevention of cardiovascular events in patients with peripheral arterial disease, stroke, diabetes or atherosclerosis.