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Ticagrelor Can Safely Follow Lytic Tx for STEMI

— Bleeding similar upon delayed adminstration of ticagrelor versus clopidogrel

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ORLANDO -- Among younger ST-segment elevation MI (STEMI) patients who can't get primary angioplasty in time, and wind up getting fibrinolytics as the main reperfusion therapy, subsequent ticagrelor (Brilinta) use may be just as safe as clopidogrel (Plavix), a randomized trial found.

The more powerful P2Y12 inhibitor, ticagrelor was non-inferior to clopidogrel when it came to the primary safety outcome of TIMI major bleeding at 30 days (0.73% ticagrelor vs 0.69% clopidogrel, P<0.001 for non-inferiority), reported Otavio Berwanger, MD, PhD, of Brazil's Heart Hospital in São Paulo, at the American College of Cardiology annual meeting.

Berwanger and co-authors of the TREAT trial had their paper simultaneously published online in .

There was no statistical difference in other defined bleeding events either, though ticagrelor recipients had numerically more minor and total bleeds. Rates of cardiovascular death, MI, stroke, recurrent ischemia, transient ischemic attack, and other arterial thrombotic events were comparable between study arms.

"STEMI guidelines recommend that ticagrelor should only be initiated after 48 hours after fibrinolysis," the authors noted. "Based on our findings, patients with STEMI younger than 75 years who initially received clopidogrel can be safely switched to ticagrelor in the first 24 hours after fibrinolysis. Whether this strategy will result in fewer cardiovascular events in the long term remains to be determined."

The TREAT investigators randomized 3,799 patients in 10 countries who had an acute ST elevations after fibrinolytic therapy to 180 mg ticagrelor (and 90 mg twice daily thereafter for 12 months) or 300 mg clopidogrel (and 75 mg a day until year's end). The phase III trial enrolled patients as early as possible after the index event, and not more than 24 hours afterward.

Berwanger acknowledged that low observed major bleeding rates made the noninferiority margin of 1% "quite wide" and reflected the more than 11-hour delay in randomizing patients after lytic therapy, as well as the modest sample size of the trial.

Another caveat was the relatively younger, lower-risk patient group compared with an older population typically seen in this setting, commented Craig Beavers, PharmD, of the University of Kentucky in Lexington, at an ACC press conference.

"This trial answers some questions, but critical others remain," according to Clyde Yancy, MD, of Northwestern University Feinberg School of Medicine in Chicago, and Robert Harrington, MD, of Stanford University School of Medicine in Stanford, California, in an.

"Converting to ticagrelor late after initial exposure to clopidogrel appears safe, as defined by a noninferior difference in major bleeding (using a wide inferiority margin). But we also await further data addressing short-term and long-term outcomes in this lower-risk population of patients with STEMI."

Importantly, it remains unknown whether ticagrelor can be used concomitantly with lytic therapy for acute revascularization, Yancy and Harrington emphasized.

"Given the worldwide burden of acute coronary syndromes and the recognized exigencies which preclude the ubiquitous availability of percutaneous coronary intervention, we believe this question needs urgent attention. We await future trials," they wrote.

This would have been studied if not for the logistics of the trial, and might have taken another 2 to 3 years to complete, Berwanger said. His group was also interested in an efficacy trial, although that would have required "another PLATO trial with 18,000 patients" on their limited funding.

The 12-month analysis of TREAT is in the works, however.

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    Nicole Lou is a reporter for Ƶ, where she covers cardiology news and other developments in medicine.

Disclosures

TREAT was funded by AstraZeneca.

Berwanger disclosed support from from AstraZeneca, Amgen, Bayer, Novo Nordisk, Boehringer Ingelheim, and Roche Diagnosis, as well as relevant relationships with AstraZeneca, Bayer, Roche Diagnosis, and Sanofi. Co-authors disclosed multiple relevant relationships with industry.

Yancy disclosed serving as a deputy editor of JAMA Cardiology. Harrington disclosed relevant relationships AstraZeneca, Bristol-Myers Squibb, Janssen, Novartis, Portola, the Medicines Company, Sanofi, CSL Limited,Amgen, Bayer, Element Science, Gilead, MyoKardia, the American Heart Association and Stanford Health Care.

Primary Source

American College of Cardiology

Berwanger O "Ticagrelor versus clopidogrel after thrombolytic therapy in patients with ST-elevation myocardial infarction: a randomized clinical trial" ACC 2018.

Secondary Source

JAMA Cardiology

Yancy CW and Harrington RA "The TREAT trial -- moving ST-elevation myocardial infarction care forward, with more to do" JAMA Cardiol 2018.

Additional Source

JAMA Cardiology

Berwanger O, et al "Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial" JAMA Cardiol 2018; DOI: 10.1001/jamacardio.2018.0612.