08 Sep THEMIS-PCI Trial: Ticagrelor in Patients with Diabetes and Stable CAD with History of PCI
MedicalResearch.com Interview with:
Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC
Professor of Medicine, Harvard Medical School
Executive Director of Interventional Cardiovascular Programs,
Brigham and Women’s Hospital Heart & Vascular Center
MedicalResearch.com: What is the background for this study?
Response: Dual antiplatelet therapy (DAPT) is known to improve outcomes in patients with acute coronary syndromes (ACS), prior myocardial infarction (MI), or recent coronary stenting. What was unknown is whether patients with diabetes and stable coronary artery disease – a group generally believed to be at high ischemic risk – would benefit from initiation of long-term DAPT with low-dose aspirin plus ticagrelor versus low-dose aspirin (plus placebo). This is what THEMIS was designed to test, with THEMIS-PCI designed prospectively to examine those patients specifically who had a history of previous percutaneous coronary intervention (PCI).
MedicalResearch.com: What should readers take away from your report?
Response: In the overall THEMIS trial – the largest trial in diabetes to date – there was a statistically significant 10% reduction in the primary efficacy endpoint which was the rate of cardiovascular death, MI, or stroke. There were consistent and significant reductions in MI, including ST-elevation MI (STEMI), ischemic stroke, and amputations or acute limb ischemia. This benefit was amplified in THEMIS-PCI, with a significant 15% reduction in the primary efficacy endpoint.
There was a significant increase in major bleeding in THEMIS, including a small, but statistically significant 0.2% excess in intracranial bleeding with DAPT, that largely consisted of traumatic subdural hematomas, mostly from falls. In THEMIS-PCI, there was no signal of excess intracranial bleeds (31 versus 33 events), and while other major bleeding was still significantly increased, the excess bleeding was not as large as in the THEMIS patients without a history of PCI. Thus, in carefully selected patients with diabetes and stable coronary artery disease who have a history of previous coronary stenting and have presumably tolerated DAPT in the past without bleeding complications, the combination of ticagrelor plus low-dose aspirin should be considered.
These trial results provide a new option to high-risk patients with diabetes and extend the populations in which DAPT is already known to be beneficial, namely ACS, prior MI, and recent coronary stenting.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We are assessing how generalizable the results of THEMIS and THEMIS-PCI may be, and our initial results suggest that there are many patients such as those in THEMIS-PCI who may benefit from this strategy of more intense anti-thrombotic therapy than just aspirin alone.
The key is making sure patients are not at elevated risk of bleeding, in which case this strategy of more intense and prolonged anti-thrombotic therapy can backfire. However, in patients at low bleeding risk, this approach can provide a substantial reduction in ischemic events involving the heart, brain, and peripheral circulation as well. Patients with prior PCI would have of course been exposed to a period of DAPT previously at the time of stenting, so such patients appear to be the best candidates for the strategy we studied. Contemporary data show that patients with diabetes and stable coronary artery disease but without a history of MI are at the same level of ischemic risk as patients with a history of prior MI but without diabetes – thus, there is a large unmet clinical need in these patients.
Disclosures: Research funding from AstraZeneca to Brigham and Women’s Hospital for my role as co-Chair and co-PI of THEMIS and THEMIS-PCI.
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
Prof Deepak L Bhatt, MD , Prof Philippe Gabriel Steg, MD , Prof Shamir R Mehta, MD, Prof Lawrence A Leiter, MD, Prof Tabassome Simon, MD, Prof Kim Fox, MD, et al.
Published: TheLancet September 01, 2019
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