Diabetes-related factors and the effects of Ticagrelor Plus aspirin in the THEMIS and THEMIS-PCI trials

Abstract

BACKGROUND THEMIS (N=19,220) and its pre-specified THEMIS-Percutaneous Coronary Intervention (THEMIS-PCI, N=11,154) sub-analysis showed in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction [MI] or stroke, that ticagrelor plus aspirin (relative to placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, or intracranial bleeding) if they had a previous PCI. OBJECTIVES In these post hoc analyses, we examined whether the primary efficacy outcome (cardiovascular death, MI, stroke; 3-point MACE), primary safety outcome (TIMI-defined major bleeding) and net clinical benefit varied with diabetes-related factors. METHODS Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications. RESULTS In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years; 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%; 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR] 0.90; P=0.04) were generally consistent across subgroups. Major bleeding event rate (overall 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR=2.32; P<0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications CONCLUSION Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.