No net benefit for ticagrelor plus aspirin over aspirin alone in patients with T2DM and stable coronary disease

Reference

Steg PG, Bhatt DL, Simon T, et al, for the THEMIS Steering Committee and Investigators. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med 2019;381(14):1309-1320.

Synopsis

Standard therapy for patients with CAD and T2DM is low-dose aspirin. These investigators identified 20,108 patients, of whom 19,271 were included in this study. All patients were 50 years or older with stable CAD (history of percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG], or at least 50% stenosis of one coronary artery) and T2DM treated with medication for at least 6 months. All patients received low-dose aspirin, and were randomized to receive ticagrelor 90 mg twice daily or placebo. Based on results from another study, the dosage was reduced to 60 mg twice daily, with approximately 75% of the patient-days of ticagrelor on the lower dose. Analysis was by intention to treat, and the groups were balanced at the beginning of the trial. The patients' mean age was 66 years, and 80% had a previous PCI or CABG. There were far more withdrawals in the ticagrelor group (34.5% vs 25.4%), with the most common symptomatic reasons being more dyspnea (6.9% vs 0.8%; number needed to treat to harm [NNTH] = 17) and bleeding (4.9% vs 1.3%; NNTH = 28). There was no difference in all-cause mortality (6.0% vs 6.2% for placebo) or cardiovascular mortality (3.8% vs 3.7% for placebo) between groups. There were slightly fewer MIs (2.8% vs 3.4%; P < .05; number needed to treat [NNT] = 167 over 40 months) and ischemic strokes (1.6% vs 2.0%; P < .05; NNT = 250 over 40 months) in the ticagrelor group. However, there were also more major bleeding events (2.2% vs 1.0%; P < .001; NNTH = 83 over 40 months) and intracranial hemorrhages (0.7% vs 0.5%; P = .005; NNTH = 500 over 40 months) in that group. The disclosure statement for the authors runs to a full page of fine print.