AstraZeneca has announced results of two separate sub-analyses of PEGASUS-TIMI 54, which investigated the long-term use of ticagrelor (Brilinta) tablets in patients with a history of myocardial infarction and at least one additional risk factor for thrombotic cardiovascular events at three years. The first subanalysis included patients with peripheral artery disease and the second with diabetes. The results of both analyses show a reduction in major adverse cardiac events (MACE) with ticagrelor plus aspirin compared to placebo plus aspirin that was consistent with the overall PEGASUS-TIMI 54 population.
These data were presented at the 2016 American College of Cardiology (ACC) meeting and simultaneously published in Journal of American College of Cardiology (JACC).
In the first subanalysis, 1,143 patients with a prior myocardial infarction and peripheral arterial disease had higher rates of MACE at three years compared to those without peripheral arterial disease, which persisted after adjusting for baseline differences, with higher risk of MACE (HR 1.60, 95% CI 1.20-2.13; p=0.0013), cardiovascular death (HR 1.84, 95% CI 1.16-2.94; p=0.0102), stroke (HR 2.31, 95% CI 1.26–4.25; p=0.0071), mortality (HR 2.05, 95% CI 1.43-2.94; p<0.001), and TIMI major bleeding (HR 1.57, 95% CI 0.47-5.22; p=0.46). Pooled doses of ticagrelor plus aspirin compared to placebo plus aspirin reduced the risk of MACE in both patients with peripheral arterial disease (HR 0.75, 95% CI 0.55-1.01) and those without (HR 0.86, 95% CI 0.77-0.96) at 3 years. TIMI major bleeding occurred more frequently with ticagrelor 90mg plus aspirin vs placebo plus aspirin (HR 1.46, 95% CI 0.39-5.43) and with ticagrelor 60mg plus aspirin vs placebo plus aspirin (HR 1.18, 95% CI 0.29-4.70).
A second sub-analysis of 6,806 patients with a prior myocardial infarction and diabetes suggested that pooled doses of ticagrelor plus aspirin compared to placebo plus aspirin reduce the risk of MACE in both non-diabetics (HR 0.84, 95% CI 0.74-0.96) and diabetics (HR 0.84, 95% CI 0.72-0.99) at three years. Similar to non-diabetic patients, there was an increase in TIMI major bleeding in diabetic patients (HR 2.56, 95% CI 1.52-4.33) treated with ticagrelor.
Marc Bonaca, ( Thrombolysis in Myocardial Infarction [TIMI] Study Group, Brigham and Women’s Hospital, Boston, USA), the lead investigator for the PAD subanalysis of PEGASUS, says: “Patients with prior MI and PAD are at further heightened risk of ischemic events relative to patients with prior MI and no PAD even when accounting for other risk factors. Because of their heightened ischemic risk, patients in the subgroup analysis with a prior MI and PAD appear to have a higher absolute risk reduction with ticagrelor than those without. These findings may be helpful to clinicians in identifying patients with prior MI who they feel could benefit from prolonged therapy with ticagrelor.”