The Cardiology Advisor: It seems like there is a theme of “out with the old, in with the new” with treatment regimens this year at ACC (eg, no more warfarin). Would you comment on that?
Dr Wells: Let me address the aspirin issue first. There was minimal evidence that aspirin was effective. There was very little risk reduction associated with it, and the data were not convincing to me that we should have been using it. It was the nuisance of warfarin that may have driven some people toward aspirin. Aspirin is really not the “old.” DOACs have actually been used longer than aspirin.
For sure warfarin is the “old,” though, and a lot of people are comfortable using it. It is difficult when you have been practicing for many years to switch over. We now have compelling evidence that DOACs are safer than warfarin, easier than warfarin, and are as or more effective than warfarin. The only downside is cost. Warfarin costs pennies a day whereas I think rivaroxaban, at least in Canada, is approximately $4 per day and even more expensive in the United States. Cost is always going to be an issue in health care. Cost is the remaining barrier here.
The Cardiology Advisor: In the accompanying editorial3 in the New England Journal of Medicine, the authors noted “this trial suggests it would be helpful to evaluate the effect of reduced doses of rivaroxaban within 6 months after an episode of VTE.” Would you say their statement is a response to the positive results from the prophylactic dose?
Dr Wells: We can keep going back in increments of duration. If you look at the outcomes that used the 20-mg doses, the dose that has been published, the outcomes are excellent. So, it’s going to be, “Who are the patients you should study to get the most bang for the buck in your research? Can we identify a group of patients at a higher risk of bleeding where it’s worthwhile studying whether the lower dose is of benefit to those patients?” Because the current doses are working fine.
It is pretty clear in all the VTE literature that the highest risk of everything — bleeding, recurrence, death — is at 3 months, and then the curves start to flatten out. But that’s [3 months] where you have to be careful and where you are going to have to carefully choose the population. Is that worthwhile doing? Sure. We try to refine treatment as much we can — that kind of precision medicine or personalized medicine, that sort of holy grail of medicine, is to be able to have the exact formula for each individual. We do it based on clinical parameters, not based on genetics or biomarkers usually, but those are there potentially, too.
The Cardiology Advisor: Where do we go from here? What are the takeaways?
Dr Wells: I think the takeaway is to not use aspirin anymore. Physicians should start using extended treatment when it is indicated and feel comfortable in the knowledge that it is effective and safe. Physicians love to practice the art of medicine instead of the science of medicine, and there is going to be a lot of art in deciding between the 10-mg and 20-mg doses, and that’s okay. It gives you a lot more flexibility.
Disclosures: The study was sponsored by Bayer Pharmaceuticals. A full list of author disclosures can be found at NEJM.org.
- Wells P; on behalf of the EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. Joint ACC/JAMA Late-Breaking Clinical Trials. Presented at: the 66th Annual Scientific Session & Expo of the American College of Cardiology. March 17-19, 2017; Washington, DC.
- Weitz JI, Lensing MH, Prins R, et al; for the EINSTEIN CHOICE Investigators. Riovaroxaban or aspirin for extended treatment of venous thromboembolism [published online March 18, 2017]. N Engl J Med. doi:10.1056/NEJMoa1700518
- Crowther MA, Cuker A. Reduced-intensity rivaroxaban for the prevention of recurrent venous thromboembolism [published online March 18, 2017]. N Engl J Med. doi:10.1056/NEJMe1701628