Diabetes Length and Meds Don’t Impression Ticagrelor Results in THEMIS

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Duration, control, and treatment of diabetes should not affect whether the potent antiplatelet drug is used, says the lead author.

For patients with type 2 diabetes and stable coronary disease who have not had MI or stroke, certain factors related to their diabetes should not necessarily come into play when doctors decide whether to add ticagrelor (Brilinta; AstraZeneca) to the treatment regimen. A post hoc analysis of the THEMIS and THEMIS-PCI studies shows. They also didn’t affect the results of the study, the investigators say.

The complex balance between efficacy and safety demonstrated in both the entire study cohort and the subgroup with a history of PCI was established by researchers led by Lawrence Leiter, MD (St. Michaels Hospital and University of Toronto, Canada) , Report.

This is important not only because diabetic patients are at a much higher risk of cardiovascular disease and events than non-diabetic patients, but also because of the prothrombotic environment caused by their disease or the secondary effects of other diabetes drugs may lead to different responses to antiplatelet therapies. Previous studies have shown that duration of diabetes is likely to influence the risk of subsequent CV events, while certain diabetes drugs – particularly sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists – reduce this risk can .

If the Results from THEMIS and THEMIS-PCI The researchers came to a two-part result in 2019: In stable CAD patients with diabetes and no previous stroke or MI, the significant increase in heavy bleeding observed with ticagrelor plus aspirin outweighed the smaller decrease in MACE. However, a more favorable benefit-risk balance was observed in the PCI subgroup, which is due to previous studies in patients at higher risk. Therefore, the researchers concluded that patients with diabetes and a history of PCI could constitute an “easily identifiable” population for whom advanced dual antiplatelet therapy with ticagrelor could be considered.

What can be gleaned from this new analysis, published in the May 18, 2021 issue of the Journal of American College of Cardiology, is a message of persistence, Senior Author Philippe Gabriel Steg, MD (Hôpital Bichat, Paris, France), said TCTMD. The lack of significant interactions with the diabetes-related factors in this post hoc analysis suggests that the overall interpretation applies to the different subgroups we are considering and that there is no particular reason to use the duration of diabetes, glucose control. or types of glucose lowering agents in the background as a method of patient selection, ”said Steg. “We’re sticking to the idea that the best people [for the addition of ticagrelor] are patients of the THEMIS-PCI type. “

No significant interactions

THEMIS researchers examined the influence of diabetes-related factors on the effects of ticagrelor plus low-dose aspirin in the study that enrolled 19,271 patients with type 2 diabetes and stable CAD with no history of MI or stroke ;; Most (58%) had a history of PCI. The median duration of diabetes among participants was 10 years and the median baseline HbA1c was 7.1%.

I would generally be much more aggressive with a diabetic who has coronary artery disease and 20 years of diabetes as opposed to a patient recently diagnosed with diabetes who shows signs of coronary artery disease. Philippe Gabriel Steg

The primary efficacy outcome was MACE (CV death, MI, or stroke) and this occurred in 8.1% overall for THEMIS and 7.3% for THEMIS-PCI. The primary safety result was profuse TIMI bleeding, which was observed in 1.6% in the overall study and in 2.0% in the PCI subgroup.

Compared to aspirin alone, the combination of ticagrelor and low-dose aspirin reduced MACE at the expense of increased TIMI bleeding in both cohorts, as previously reported. These effects were not significantly changed by the duration of the diabetes, the HbA1c level or the use of various important antihyperglycemic drugs (P = NS for all interactions).

Researchers also assessed a net clinical outcome that included all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding, and found no difference between treatment arms across the THEMIS study (HR 0.93; 95% CI 0.86-1, 02) Advantage for ticagrelor plus aspirin in the PCI subgroup (HR 0.85; 95% CI 0.75-0.95). These results also did not differ on the basis of the diabetes-related factors assessed in this post-hoc analysis (P = NS for all interactions).

“This adds to the robustness of the THEMIS-PCI results and to the suggestion that this is the optimal group for treatment with ticagrelor added to aspirin,” said Steg.

Change treatment decisions

Although the information in this study should not be used to make decisions about ticagrelor use in these types of patients, the results provide clinicians with powerful data, said Steg, noting that the risk of MACE is strongly related to longer duration of diabetes and a higher HbA1c in THEMIS and THEMIS-PCI. In particular, the association with duration is not very much appreciated and should be considered when treating patients, he said.

“I would generally be much more aggressive in my management of a diabetic with coronary artery disease and 20 years of diabetes as opposed to a patient recently diagnosed with diabetes and showing signs of coronary artery disease,” advised Steg. “And I think we need to be stricter with all prevention options, be it lifestyle, lipid or blood pressure control, examining the extent of the disease, and so on and so forth.”

As for ticagrelor, “I think it’s probably not a treatment that meets the criteria for everyone,” said Steg. “I think that even with patients who look like THEMIS-PCI patients, it probably has to be a medical decision as there are risks and benefits. Therefore, you will likely need to weigh this risk versus ischemic risk for each patient based on your perception of bleeding. “

Jean-Guillaume Dillinger, MD, PhD, and Patrick Henry, MD, PhD (both Hôpital Lariboisière, Paris, France) make a similar point in an accompanying editorial. “The combination of ticagrelor and aspirin is a new treatment option for selected patients with diabetes mellitus who are at high risk for CV. This option should be considered after a careful bleeding risk assessment and considering several factors such as duration of diabetes mellitus, HbA1c level and previous PCI, ”they write.