Adding ticagrelor to aspirin results in 8 fewer MIs and 9 more major bleeds per 1000 patients with CAD, T2DM, and PCI

Reference

Bhatt DL, Steg PG, Mehta SR, et al, for the THEMIS Steering Committee and Investigators. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial. Lancet 2019;394(10204):1169-1180.

Synopsis

This is a substudy of the larger THEMIS trial focusing on the 11,154 patients who had a previous PCI. In the overall study, all patients were 50 years or older with stable CAD (history of PCI or coronary artery bypass graft, or at least 50% stenosis of one coronary artery) and type 2 diabetes mellitus treated with medication for at least 6 months. They all received low-dose aspirin (75 to 150 mg), and were randomized to receive ticagrelor 90 mg twice daily or placebo. Based on results from another study, the dose 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 patients were followed up for a median of 40 months. The groups were well balanced, with a median age of 66 years. The authors do not report it here (even in the appendix), but the percentage lost to follow-up was much higher in the overall study population (34.5% vs 25.4%), with the most common symptomatic reasons being dyspnea (6.9% vs 0.8%; number needed to treat to harm [NNTH] = 17) and bleeding (4.9% vs 1.3%; NNTH = 28). In this substudy of those patients with previous PCI (as in the overall study population), there were no differences in all-cause mortality (3.1% vs 3.9% for placebo) or cardiovascular mortality (3.1% vs 3.3% for placebo), but there were fewer myocardial infarctions (3.1% vs 3.9%; P = .03; number needed to treat [NNT] = 125 over 40 months). There was no reduction in ischemic stroke. Major bleeding was more common (2.0% vs 1.1%; P < .0001; NNTH = 111 over 40 months) in the ticagrelor group. However, there was no difference in the likelihood of fatal bleeding (6 events in each group) or intracranial hemorrhage (33 in the ticagrelor group and 31 in the placebo group). Overall, the balance of benefits and harms was more favorable in the subset of patients who had previously had PCI than in those who had not.