Patients with stable coronary artery disease (CAD) and diabetes mellitus with or without previous percutaneous coronary intervention (PCI) are at high risk of ischaemic events. Two new trials presented at the ESC Congress 2019 now report that in these patients, ticagrelor added to aspirin significantly reduces the incidence of ischaemic events, but increases the risk of major bleeding compared with placebo plus aspirin.

Credit: V. Summersby/Springer Nature Limited

Dual antiplatelet therapy (DAPT), a combination of aspirin plus a P2Y12 receptor inhibitor, has been shown to improve outcomes for patients with acute coronary syndrome (ACS) or after coronary stenting. Patients with both CAD and diabetes are at high risk of ischaemic events, in part owing to increased platelet activation that is associated with insulin resistance. As such, aspirin treatment alone might not provide adequate protection for this high-risk population. The benefit of long-term DAPT on the risk of ischaemic events was explored in two patient populations with stable CAD and diabetes in the THEMIS and THEMIS-PCI trials.

In the randomized, double-blinded THEMIS trial, 19,220 patients with stable CAD and diabetes with no history of myocardial infarction (MI) or stroke were randomly assigned to receive ticagrelor plus aspirin or placebo plus aspirin. The median duration of follow-up was 39.9 months. The incidence of cardiovascular death, MI or stroke (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% versus 8.5%; HR 0.90, 95% CI 0.81–0.99, P = 0.04). However, the ticagrelor group had a higher incidence of major bleeding (as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria) than the placebo group (2.2% versus 1.0%; HR 2.32, 95% CI 1.82–2.94, P < 0.001). Ticagrelor treatment was also associated with a slight excess of intracranial haemorrhage.

The THEMIS-PCI trial was a prespecified subgroup analysis of the THEMIS trial that was conducted to analyse the efficacy and safety of adding ticagrelor to aspirin in 11,154 patients who had previous PCI. Ticagrelor treatment was associated with fewer primary efficacy outcomes than placebo (7.3% versus 8.6%; HR 0.85, 95% CI 0.74–0.97, P = 0.013). The incidence of TIMI major bleeding was significantly higher in the ticagrelor group, but the rates of fatal bleeding and intracranial haemorrhage were not significantly different between the groups.

“In carefully selected patients with diabetes and stable CAD who have a history of previous coronary stenting and have presumably tolerated DAPT in the past without bleeding complications, the combination of ticagrelor plus low-dose aspirin should be considered,” explains Deepak Bhatt, who was involved in both trials. “These trial results provide a new option for high-risk patients with diabetes and extend the populations in which DAPT is already known to be beneficial, namely ACS, prior MI and recent coronary stenting.”