New Analyses and Exciting Trial Data at AHA 2022, with Marc Bonaca, MD

Marc Bonaca, MD

The American Heart Association (AHA) Scientific Sessions 2022 in Chicago was host to a plethora of exciting new conversations surrounding the biggest trial data in the cardiology arena, with big discoveries potentially shaping the future of care.

In an interview with HCPLive at AHA 2022, Marc Bonaca, MD, Executive Director, CPC Clinical Research, provided perspective on new analyses of the VOYAGER-PAD trial, exciting trial data he found to be the most crucial, and other important discussion topics, like the significance of providing a platform for the patient voice.

Here is a lightly edited transcript of our conversation.

HCPLive: To start off, could you provide the key highlights from the new analyses of the VOYAGER-PAD trial on rivaroxaban and how they complement previous findings from the trial?

Bonaca: We provided several new analyses from VOYAGER-PAD at this meeting. Some of these, we're really trying to understand the biology of vascular disease, outcomes of vascular disease, and some of the risk stratification approaches. And then we looked at some subgroups that are really relevant to this meeting, including those with critical limb ischemia getting endovascular surgical treatment.

We have a poster looking at the causes of death in patients with peripheral artery disease overall, and those with and without coronary disease. One of the big mysteries in PAD is why patients with PAD respond differently to antithrombotic therapies than patients who have CAD. The best example of this is the EUCLID trial, which was neutral to Ticagrelor versus Clopidogrel.

Whereas the PLATO trial, which was a CAD trial, showed a mortality benefit. What we showed in that analysis was that actually a minority of deaths are atherothrombotic in PAD, there's a lot of other causes of death such as infection, cancer and other things. Actually, the dominant morbidity overall is limb outcomes and that CV death or coronary heart disease death really depends on whether or not they have coronary disease. That was an interesting descriptive analysis.

A second analysis looked at applying some of the risk stratification schemes that have been developed around amputation risk. There's one called WIFI that looks at the status of wound infection and ischemia in patients with foot wounds or critical limb threatening ischemia with risk of amputation. We tried to validate that in VOYAGER-PAD. Although it did predict amputation risks, its performance was modest. And we actually found something very simple, which including patient characteristics such as diabetes, improved the discrimination of the score, at least showed great differences between those with and without diabetes.

The third one was looking at a very controversial topic, which was the association of blood pressure and amputation in patients with PAD. There’s been an analysis from a large trial called all hat, which looked at blood pressure lowering. It showed an inverse association between blood pressure and amputation risk. So as blood pressure got lower, amputation risk went up below a certain threshold. Now, this idea that higher blood pressures may be necessary for end organ perfusion is one that we use in stroke. So when people come down with a stroke, we allow their blood pressure to be higher and even renal ischemia. But that hasn't been really shown robustly for PhD. We looked in VOYAGER, at the association of blood pressure and outcomes, and we saw the same thing actually. Lower blood pressures were associated with higher rates of adverse limb outcomes.

The fourth one is the one I mentioned around critical limb threatening scheming. It's been a hot topic at AHA because of the BEST-CLI Trial. We looked at the patients treated with endovascular versus surgical. High rates of adverse limb events after both procedures. And we found that rivaroxaban actually significantly reduced those limb outcomes, regardless of whether they're treated with surgery or endo, and bleeding risk appeared the same. However, in the endo patients that got clopidogrel, clopidogrel seemed to increase bleeding. The message is that rivaroxaban works, regardless of the procedural approach, and tries to mitigate bleeding by reducing the duration of dual antiplatelet therapy (DAPT).

HCPLive: What other trial data has been exciting at AHA?

Bonaca: There have been really nice learnings here at the American Heart Association. A few trials really got my attention. TRANSFORM-HF looked at the choice of diuretic in patients with heart failure, showing that furosemide or torsemide are both reasonable choices. The PROMINENT trial really put the final word on fibrates in terms of their role in cardiovascular disease and the adverse events, renal endpoints, I think that got my attention. It's probably the end of the line for that group of drugs.

More data on eicosapentaenoic acid (EPA), a controversial topic after the REDUCE-IT trial. An approved drug that I do use, but some biomarker evidence that suggested that maybe the placebo group had some adverse effects related to mineral oil. Here, another smaller trial, but looking at the effects of EPA that will add to the controversy. The PRECISE trial is looking at CT-FFR for predicting and reducing ischemic events, a really exciting trial there. Then, as I mentioned, the BEST-CLI is going to have a big impact.

HCPLive: To your point about mineral oil, do you think that it's a legitimate safety concern? Or are you a little bit on the fence?

Bonaca: For REDUCE-IT, you know, boy, I’ll say it’s not straightforward. I do think that the biomarker data are concerning that mineral oil was not benign. That being said, the benefits seen in the trial are so overwhelming that even if that explains some of the benefits, it is probably not all of them. I think that it is probably somewhere in between, but I do think this next trial is not going to make it a simpler picture.

HCPLive: What is the evolving role of patient reported outcomes and its greater emphasis on highlighting the patient voice on care?

Bonaca: It’s a really important concept. We, I think, for too long have thought a bit paternalistically about medical care. Not only do we really have to focus on shared decision making, but also understand the role of patient reported outcomes (PRO) in terms of how we evaluate endpoints.

There are various ways of thinking about this. I had a fairly impactful example at my own clinic. I was thinking about a PRO around minor bleeding and a trial is called minor bleeding, or non-relevant bleeding. I was actually engaged in a PRO with a patient around this. When I really probed enough, I realized or he told me that for him, bruising was not a minor thing. He actually reduced his dose of anticoagulant on his own whenever he got bruising, because he felt like it was a problem. We really need to understand patient reported outcomes and patient voice and how we think about not only the benefits of drugs, but benefit-risk.

HCPLive: Do you have any final thoughts?

Bonaca: I'll just say it's such a pleasure to have AHA in person. I think the greatest accomplishment of these now newly in-person meetings is to accelerate collaboration and science and to bring the community together. It's been a wonderful opportunity to be in Chicago and meet with colleagues and I think it'll translate into better research and better outcomes for patients.