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THEMIS: Diabetes-Related Factors and Effects of Ticagrelor + Aspirin
Quick Takes
- The combination of ticagrelor plus aspirin resulted in generally consistent and favorable net clinical benefit across the various diabetes-related factors in the THEMIS-PCI, but not in the overall THEMIS population..
- Ticagrelor plus aspirin reduced the incidence of MACE regardless of baseline duration of diabetes and baseline HbA1c, but at the expense of major bleeding events.
- Additional prospective studies are indicated to assess the safety and efficacy of ticagrelor plus aspirin for secondary prevention in patients with diabetes taking new classes of antihyperglycemic agents.
Study Questions:
What is the impact of diabetes-related factors on the primary efficacy outcome, primary safety outcome, and net clinical benefit varied in the THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) and THEMIS-PCI trials?
Methods:
The investigators conducted a post hoc analysis to examine whether the primary efficacy outcome (cardiovascular death, myocardial infarction [MI], stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction [TIMI]–defined major bleeding), and net clinical benefit varied with diabetes-related factors in the THEMIS and its prespecified THEMIS-PCI trials. The primary efficacy outcome was the time to first occurrence of a 3-point MACE composite of cardiovascular death, MI, or stroke. The primary safety outcome was major bleeding, per the TIMI definition. Net clinical benefit was a prespecified exploratory endpoint consisting of irreversible harm events and was evaluated as time to first event of the composite of all-cause mortality, MI, stroke, fatal bleeding, or intracranial bleeding. For time-to-event analyses, Cox proportional hazards models were used, with the treatment group as the explanatory variable.
Results:
In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and hemoglobin A1c (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.
Conclusions:
The authors concluded that 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.
Perspective:
This post hoc analysis reports that in the THEMIS-PCI, but not the overall THEMIS population, the combination of ticagrelor plus aspirin resulted in generally consistent and favorable net clinical benefit across the various diabetes-related factors examined. Overall, ticagrelor plus aspirin reduced the incidence of MACE regardless of baseline duration of diabetes and baseline HbA1c, but at the expense of major bleeding events. Given the post hoc nature of this study, additional studies are indicated to prospectively evaluate the safety and efficacy of therapy with ticagrelor plus aspirin for secondary prevention in patients with diabetes taking new classes of antihyperglycemic agents.
Clinical Topics: Anticoagulation Management, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Invasive Cardiovascular Angiography and Intervention, Prevention
Keywords: Anticoagulants, Aspirin, Diabetes Mellitus, Hemoglobin A, Glycated Hemoglobin A, Hemorrhage, Hypoglycemic Agents, Intracranial Hemorrhages, Metabolic Syndrome, Myocardial Infarction, Myocardial Ischemia, Outcome Assessment, Health Care, Percutaneous Coronary Intervention, Purinergic P2Y Receptor Antagonists, Secondary Prevention, Stroke, Thrombolytic Therapy
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