Dr E. Magnus Ohman: GEMINI-ACS-1 Trial a "Building Block" for Research on Rivaroxaban in ACS

E. Magnus Ohman, MD, FRCPI, FESC, FACC, FSCAI, professor of medicine at Duke University Medical Center, discussed the results of the GEMINI-ACS-1 trial comparing rivaroxaban and aspirin in acute coronary syndrome (ACS), which he and his co-authors presented at the American College of Cardiology 66^th Scientific Session. They found no significant differences in the primary endpoints and ischemic outcomes, though further research will be necessary to inform clinical practice.

Transcript (slightly modified)

Can you describe the rationale and study population of the GEMINI-ACS-1 trial?

We designed the GEMINI-ACS-1 trial on the hypothesis that we know that aspirin has been a very successful therapy in acute coronary syndrome now for decades. We have added antiplatelet therapy in the form of clopidogrel and ticagrelor too, to form dual antiplatelet therapy. But we’ve also known for a long time that the coagulation system is an important player in thrombosis, that we have not had any therapies that address this. We also got to understand more recently that aspirin has some bleeding issues with it, so the question comes up, can you then replace aspirin with a more contemporary therapy that may actually be associated with better outcomes?

What we did was we did a phase 2 trial which is sort of a preliminary, step-building trial, to try to understand in the field of acute coronary syndrome if you could replace aspirin with rivaroxaban, then what would the outcomes be. So it’s a standard ACS trial, randomizing patients between rivaroxaban and aspirin; low-dose rivaroxaban, 2.5 mg twice daily versus aspirin 100 mg daily, on top of either clopidogrel or ticagrelor, chosen by the investigator based on what they had been started on in the early phase of acute coronary syndrome.

What were the outcomes of the study?

The outcomes of the study were predominantly looking at clinically significant bleeding, and when we talk about that, this is just important because we have to understand if the therapy’s safe to move onto a larger phase 3 trial. The primary endpoint was non-CABG [coronary artery bypass graft] clinically significant bleeding up to 1 year.

We found that rivaroxaban and aspirin performed very similarly. The bleeding rates were just about 5% in both arms, this was not a statistically significant difference. Naturally, when we do a study like this we would also want to look at what we call the ischemic outcomes, in this case, cardiovascular death, MI [myocardial infarction], and stroke, and stent thrombosis. Here also, we find no difference between aspirin and rivaroxaban, which is encouraging, but I have to emphasize that this trial is not large enough to detect meaningful differences here and so it shouldn’t change practice or how we do things today.

The one area that was of particular interest to us was stent thrombosis, it’s a much feared complication among patients having PCI [percutaneous coronary intervention], and in this study, although small numbers, showed no difference.

So this is a very nice building block to move on to understanding this field better and do a larger trial that will really try to ascertain these issues.

What is the significance of these findings for clinical practice?

The only aspect of this which may be of interest is that this is actually historic. Aspirin has been a foundation therapy for a long time, and we have asked the question: can it be replaced? While we can’t say that it definitely can be, we’ve actually started the process that may get us to much better targeted therapies for the future.