Rivaroxaban Demonstrates Favorable Benefit-Risk Profile in Fragile Populations with Peripheral Arterial Disease

In an interview with Pharmacy Times, cardiologist and vascular medicine specialist, Marc Bonaca, MD, department of medicine, division of cardiovascular medicine, University of Colorado, Anshutz Medical Campus, Aurora, Colorado, discussed the importance of the VOYAGER PAD results. Further information will be presented during the American Heart Association conference in Philadelphia, Pennsylvania (November 11, 2023, to November 13, 2023).

Pharmacy Times: Can you provide an overview of the key findings from the study, especially concerning the outcomes in patients with peripheral arterial disease (PAD) who are considered “fragile”?

Marc Bonaca: VOYAGER PAD looked at the risk and benefit of rivaroxaban patients with symptomatic PAD after revascularization. In this sub analysis, we looked at an important question, which is how did the balance of efficacy and safety and how did the benefit-risk look those patients that we defined as “fragile”, meaning those that were elderly, low body weight, or had chronic kidney disease (CKD), and these are all features that often are associated with bleeding risk and make clinicians worried sometimes about benefit-risk.

Pharmacy Times: The concept of "fragile patients" is defined based on specific criteria such as age, weight, and baseline eGFR. How were these criteria determined, and why was it important to categorize patients this way for this study?

Bonaca: There are many definitions of “fragility” that are out there, and so many of them are intended to capture the same concept: somebody who is at higher risk, but may also be at higher risk of adverse outcomes like bleeding. We used a pre specified definition, it was based on age, kidney function, and body weight, although there are other definitions as well. Certainly, when you look at the data, those criteria did capture a group of patients that were higher risk for both ischemic events and bleeding events, so, I think we did capture that intended population. And I think it's important because for clinicians, it's often a difficult decision how to treat patients that have those criteria.

Pharmacy Times: How does the reduction in total vascular events contribute to the overall assessment of the efficacy of rivaroxaban in this patient population?

Bonaca: What’s really novel about this analysis is we didn't just look at first events or a narrow group of events. We know we take care of patients are many things that happen, so we looked at total vascular events and looked at the spectrum of things that happen. This includes recurrent events, we know for a lot of patients, if they have acute limb ischemia that may be followed by multiple revascularizations, amputation, for patient all of that matters. So, we looked at the totality of risk, we saw that the event rates are extremely high, so if you looked for 100 patients followed over 3 years, you'd have 99 events. That’s an incredibly high event rate. We looked at the efficacy of rivaroxaban, not only was efficacy consistent with patients who weren't fragile, but there was a greater absolute benefit, more procedures avoided—I think it was something like 15 to 20 procedures avoided for those 100 patients—over 3 years. I think that tells us that we don't want to undertreat that population.

The other side of that is safety, but the safety also was reassuring. It was consistent with the safety that we saw in the non-fragile patients, so, from a benefit-risk perspective, there's still very favorable benefit risk profile to the therapy.

Pharmacy Times: Were there any unexpected or notable findings regarding same-day vascular events?

Bonaca: The magnitude of recurrent events was striking, and for those that see these patients in the clinic, it won't be a surprise that when something bad happens [to a patient], they are often multiple bad things that had happened, but it was probably even more dramatic than we expected.

Pharmacy Times: Given that rivaroxaban showed benefits in both fragile and non-fragile patient populations, how might these findings impact the approach to antithrombotic therapy in high-risk PAD populations?

Bonaca: I think the clinical take-home here is that there's a tendency to undertreat, particularly with antithrombotic patients who are low body weight, have CKD, and are elderly. And I think now there are data to show that there's a favorable benefit-risk, and I think of this a lot like atrial fibrillation (AFib). So, with patients with AFIB, we would still anticoagulate someone, even if they're elderly or if they have risk factors because we worry about stroke…Now we see that the PAD patient after revascularization that there are so many recurrent bad events that occur in those patients that we really should consider using effective therapies. You may struggle with the patient in front of you seeing what's the benefit-risk, but now you have a large data set, where you can actually look at what the benefit-risk is and engage in shared decision making with your patients.

Pharmacy Times: How can these data guide health care professionals, particularly pharmacists, in tailoring treatment strategies for individual patients with PAD?

Bonaca: Yeah, I think pharmacists play a key role here, not only do they help with educating our patients about why they're taking the drugs, they are educating clinicians about, who are the appropriate patients [who should be receiving these drugs], where are the inclusion-exclusion, but I think there's a really important factor here.

Recently, there were publications on the Beers Criteria, which preferred some [direct oral anticoagulants] to others for AFib, we're talking about something entirely different. We're talking about vascular protection. There is only 1 approved agent at 1 approved dose for vascular protection. In fact, using other agents at different doses probably increases the bleeding risk quite significantly. And so, I think it is really helpful when our pharmacists teach us—for this indication—this is the agent at the dose that you should utilize and I think using off-label doses of other drugs is quite dangerous here.