Paris, France – 1 Sept 2019: The combination of ticagrelor and aspirin reduces ischaemic events compared with aspirin alone in patients with stable coronary artery disease and diabetes. The late breaking results of the THEMIS trial are presented in a Hot Line Session today at ESC Congress 2019 together with the World Congress of Cardiology(1) and published in the New England Journal of Medicine(2).
Senior author Professor Deepak L. Bhatt of Brigham and Women’s Hospital and Harvard Medical School, Boston, US said: “In the overall population studied in THEMIS, the reduction in important ischaemic events was somewhat counterbalanced by the increase in bleeding. Therefore, it remains critical to identify which patients are at high ischaemic risk, but low bleeding risk, who could benefit from ticagrelor and aspirin.”
Patients with diabetes often develop coronary artery disease, with millions of such patients worldwide. Given the global obesity epidemic, rates of diabetes are increasing – rapidly so, in certain parts of the world. Those with both conditions are at high risk of heart attack, stroke, and amputations, in part due to an excess tendency for the blood to clot. Aspirin is generally used to decrease this risk, but cardiovascular events still occur at a high rate.
The THEMIS trial(3) examined whether adding the antiplatelet drug ticagrelor to aspirin would reduce the risk of thrombotic events in these patients. The study enrolled 19,220 patients at 1,315 sites across 42 countries in North America, South America, Asia, Africa, Australia, and Europe. Patients were 50 years or older, had type 2 diabetes, and had stable coronary artery disease (defined as a history of percutaneous coronary intervention, bypass grafting, or angiographic stenosis of 50% or more in at least one coronary artery). Patients with known prior myocardial infarction or stroke were excluded.
Participants were randomly allocated to ticagrelor versus placebo, both on top of aspirin. The primary efficacy outcome was the composite of cardiovascular death, heart attack, or stroke. The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. The median follow-up was 39.9 months.
The incidence of the primary efficacy outcome was lower in the ticagrelor group than in the placebo group (7.7% versus 8.5%; hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.81–0.99; p = 0.038). The incidence of TIMI major bleeding was higher in the ticagrelor versus placebo group (2.2% versus 1.0%; HR 2.32; 95% CI 1.82–2.94; p<0.001).
Prof Bhatt said: “There was a significant reduction in the primary endpoint of cardiovascular death, heart attack, and stroke with ticagrelor versus placebo. In addition to heart attack and stroke, acute limb ischaemia and major amputations were also reduced with ticagrelor. Major bleeding was significantly increased.”
Pinpointing subgroups of patients who could benefit from ticagrelor plus aspirin is crucial, said Prof Bhatt. “These are the patients at high ischaemic risk, but low bleeding risk. In particular, those who have previously tolerated dual antiplatelet therapy without any bleeding complications seem to be the best candidates for prolonged therapy with ticagrelor and aspirin.”
He noted that THEMIS-PCI, a prespecified subgroup analysis also presented at ESC Congress today and published in The Lancet, identified patients with the best balance of benefit versus bleeding risk. Prof Bhatt said: “In patients with diabetes and stable coronary artery disease with a history of previous coronary artery stenting who have tolerated dual antiplatelet therapy previously without any bleeding, prolonged therapy with ticagrelor and aspirin provides substantial gains in reducing the full spectrum of coronary, cerebral, and peripheral ischaemic events.”