Consulting the COMPASS for Rivaroxaban’s Role in Peripheral Vascular Disease

LAS VEGAS, NV—The role of rivaroxaban in the treatment of patients with peripheral vascular disease was the topic of multiple presentations, panel discussions, and audience questions here last week at VIVA 2018. While experts discussed the data and quizzed each other on how clinicians should incorporate it, many admitted to lingering uncertainty.

In October, a little more than a year after the 27,395-patient COMPASS trial was stopped early due to what the drug makers termed “overwhelming efficacy,” the US Food and Drug Administration (FDA) expanded indications for rivaroxaban (Xarelto; Bayer/Janssen) to include patients with stable atherosclerotic vascular disease, both CAD and PAD. COMPASS showed that rivaroxaban (2.5 mg twice daily) and low-dose aspirin (100 mg/day) cut the risk of the composite primary outcome of CV death, MI, or stroke by an absolute 1.3% versus low-dose aspirin alone, but increased the risk of major bleeding by an absolute 1.2%.

In one VIVA session, researchers debated whether the results of COMPASS would impact the ongoing CREST-2 trial, which is assessing whether contemporary revascularization with either carotid artery stenting (CAS) or endarterectomy plus intensive medical therapy reduces the risk of stroke or death within 30 days when compared with intensive medical therapy alone. Patients will be followed out to 4 years.

In his presentation, William A. Gray, MD (Lankenau Heart Institute, Wynnewood, PA), broke down the COMPASS data as they applied to the PAD population. While low-dose rivaroxaban and aspirin showed a statistically significant advantage over low-dose aspirin alone for CV death, MI, or stroke, the trial’s cohort of 7,470 patients with PAD is fairly small, he noted. Additionally, the stroke rate was the same, at 2%, in patients on rivaroxaban alone and those on aspirin alone. While that was double the 1% rate of stroke seen in the low-dose-rivaroxaban and aspirin group, Gray said, “if you do the numbers, it’s actually less than a 1% difference.”

Overall, he said, the gain from rivaroxaban for PAD patients would most likely be a modest one. Gray added that he has spoken to a principal investigator of CREST-2 who said the steering committee members "were not impressed" enough by the COMPASS results to recommend rivaroxaban be added to the medical therapy protocol of the trial at this time.

Trying to Get a Handle on the Data

In another session, Sahil A. Parikh, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), acknowledged that many physicians, himself included, are wrestling with how to integrate the PAD and carotid disease data from COMPASS.

"I can't say that I've gotten my head around that,” he said. “Many of my patients also have coronary disease, and many have had revascularization. I'm struggling a bit because many are on prolonged DAPT to reduce long-term cardiovascular events."

Panelist Thom Rooke, MD (Mayo Clinic, Rochester, MN), said institutions likely will need to sit down and have multispecialty discussions in order to come to a consensus about how to interpret the rivaroxaban data and how they want to incorporate it in their treatment paradigms.

"I don’t know how any individual is going to decide how to revamp their practice yet on the available data,” Rooke said. “I know I'm still confused.”

Sitting in the audience during the same session, Joshua Beckman, MD (Vanderbilt University Medical Center, Nashville, TN), commented, “I would feel comfortable giving [rivaroxaban] to every patient who came in for a carotid procedure and then had the procedure. That is an incredibly ripe population for this treatment.”

Panelist Geoffrey Barnes, MD (University of Michigan, Ann Arbor), said his focus with regard to prescribing rivaroxaban is in “higher-risk patients who have atherosclerosis in more than one bed, for example, and something else needs to be done [beyond monotherapy].”

That sentiment was echoed by Gray, who said that while he too is still trying to decide which patients will benefit most from the drug, he would reserve it for the polyvascular patient. In his analysis of the COMPASS impact on CREST-2, however, he cautioned that at 3.5% the annual risk of major bleeding with low-dose rivaroxaban and aspirin is not small and appears to be cumulative.

Barnes added that while cost also will remain an issue for rivaroxaban in a variety of patient subsets, the potential for it to help in those at highest risk demands frank discussion.

“We want to maximize their benefit,” he said. “So that's why I'm looking at this for those patients as opposed to dual antiplatelet therapy. I’m making sure that they're on high-dose statins, and that their blood pressure is controlled. But if they're really high risk and they’re motived to reduce that risk, I think this becomes a really nice option for them."

Despite the questions and ongoing discussions, Marc Bonaca, MD (Brigham and Women's Hospital, Boston, MA), said the good news for patients with peripheral vascular disease is that “we’ve reached an era where we know that we need to personalize therapy and stratify people. Prior guidelines have handled all PAD patients the same way, and I think that's going to evolve.”

He told TCTMD the focus for the future should be on choosing therapies and goals that will benefit individual patients with peripheral vascular disease.

“We’re also seeing more efforts being made to really educate our patients about lifestyle interventions and following through with them even though that is admittedly challenging,” he observed. Bonaca concluded that it is reassuring for clinicians and patients to have so many options and to see new data emerging that will continue to shed light on how best to attack peripheral vascular disease and improve quality of life for patients.