Optimizing Surgical Care Through Clinical Trials with Dr. Shipra Arya

In this episode of Scrubcast, host Rachel Baker sits down with Dr. Shipra Arya, a professor in the Division of Vascular Surgery at Stanford University, to discuss her journey into vascular surgery and her groundbreaking clinical trials. The conversation first delves into her recent PAUSE trial, which focuses on improving outcomes for frail patients undergoing surgery by fostering multidisciplinary collaboration. As she prepares to share her findings, Dr. Arya expresses her passion for advancing health services research and optimizing patient care.

The discussion also explores Dr. Arya's new WARRIORS trial, which will address the critical issue of sex-specific screening guidelines in vascular health, particularly abdominal aortic aneurysms (AAAs) in women. Dr. Arya emphasizes the need for tailored research to better understand the risk factors for women, citing the inadequate application of existing male-centric data. With an insightful commentary on leadership in surgery and personal growth, Dr. Arya shares her commitment to making meaningful contributions to her field while leading with a team-oriented approach.

Learn more about the WARRIORS Trial.

*Music By Nastelbom*

Rachel Baker: [00:00:00] Welcome to Scrubcast, where we take a closer look at the research happening at Stanford University's Department of Surgery. I'm your host, Rachel Baker. Today, we're speaking with Dr. Shipra Arya. It's so great to have you here.

Shipra Arya: Thank you for having me, Rachel. It's a pleasure to be here.

Rachel Baker: Thank you for joining us.

Dr. Arya is a professor in our Division of Vascular Surgery. How did you get into vascular?

Shipra Arya: That's a great question. You know, I joined general surgery thinking I would probably be a surgical oncologist, honestly. Really? Uh, and then I veered across different specialties and changed my mind till I did my vascular rotation, where I got to put a few stitches into aorta doing an aortobifemoral bypass.

Just turned out my chief resident was on vacation, so I was the primary assistant to the faculty that day, and I think that changed my whole [00:01:00] trajectory.

Rachel Baker: Wow ...

Shipra Arya: So yeah- I was hooked on vascular, and then I explored it further, and I liked everything about it. You can operate in any part of the body. You can do open. You can do endo. You just create new blood vessels out of thin air. So yeah, that was super exciting, and I still love it. The patients are complex, but I still love to do vascular and operate, so...

Rachel Baker: Amazing. Aortas really do have that kind of life-changing quality when you see one, I think, for the first time. I was just like, "Wow, that's really big."

Shipra Arya: Yeah. Yeah, every time I do an open aorta case, the student in the room, I watch their reaction, and when they get to put their hand on the aneurysm.

Rachel Baker: Mm-hmm.

Shipra Arya: It's... It can be life-changing, yes.

Rachel Baker: Yes. Well, you are a past president of the Surgical Outcomes Club and a leader in the field of health services research, particularly on the subject of frailty. You also serve on multiple [00:02:00] committees representing VA surgeons, and I feel like all of those interests really came together on your recent PAUSE trial, which stands for Patient-Centered Multidisciplinary Care for Veterans Undergoing Surgery. I understand why you gave it an acronym; it's a mouthful.

What were the goals of this trial?

Shipra Arya: This trial is a labor of love, I would say, my first major trial as a primary, like, PI. And the goals of this trial were that we knew for a long time that frailty is bad for our patients. But where there's no consensus. Once you know a patient is frail, what do you do about it, you know?

…especially in the preoperative setting, can you modify frailty or can you identify it early enough to mitigate some of the effects of it on our patients? So that was the whole goal. We knew from, like, single center studies that if you identify frailty prior to surgery, [00:03:00] it heightens the awareness, and something changes.

And whether it's more multidisciplinary collaboration between surgery or anesthesia or getting palliative care involved or, you know, maybe doing prehabilitation. And all these things have been studied at individual studies, single center studies. So our goal was can we combine all of this together to make like a multidisciplinary board where all these different stakeholders that are not involved in a patient's usual surgical pathway, like a patient does not see geriatrics or palliative care preoperatively or does not see social work or case management unless absolutely needed, or does not see nutrition and PT unless the surgeon is really, like, trying to do the prehab.

So if we bring all of these different stakeholders together along with surgery and anesthesia and created a board to optimize these frail patients, then can we change their outcomes? So that was the main [00:04:00] goal of the trial. We are nearing the end of all the analyses and getting ready to submit our findings.

So there's some interesting findings to come and hopefully we'll add to the literature of why we should be doing this

Rachel Baker: Fantastic. I'm looking forward to reading it. But you really don't rest on your laurels, or rest at all. You have a new trial, and it's called WARRIORS. You're looking at AAAs in women. This feels like a big departure from your previous work, so what caused you to switch gears?

Shipra Arya: That's, you know, a great question. I believe it was serendipity, I think, where I was not thinking about aneurysmal disease in particular or sex-based differences. I had done some retrospective reviews on sex-based differences and looking at it from a lens of health services research, where [00:05:00] being female is a risk factor for poor outcomes within vascular, and we've seen that in various studies.

But I was approached for being the US PI of this larger international effort by Janet Powell, who was a huge name in aortic research. So, she approached me about three years ago at the sponsorship of Dr. Ron Dalman, our prior division chief, as he is big into aortic research, and he has his own LIMIT trial ongoing, testing metformin versus placebo for small AAAs. So Janet wanted the US to be part of this larger international effort, and US would obviously be, like, the biggest contributor of patients.

And Ron introduced us, then I spoke to her about the trial. I spoke to her about my experience with PAUSE and other sub-investigator, co-investigator studies. She was very interested in me taking the leadership role along with Adam Beck at University of [00:06:00] Alabama.

And we started working on it three years ago, got through what's called GCRFF, which is a Global Cardiovascular Research Funders Forum. It has funding agencies from all over the world, like British Heart Foundation, NHLBI. So to try and jumpstart cardiovascular disease trials that need multiple countries just to reach the power, because you can't get enough sample size in just one country. So that body first approved the entire study, the endpoints, the methods, then each country went back to their respective funding agencies to get funding.

So then in 2023, we began a process of working with NHLBI to get them to approve the US study. And we finally got that through after multiple rounds of consultations, then scientific review, and now we are finally funded for this study.

Rachel Baker: Oh my gosh. So complex.

Shipra Arya: I know. So... I do wanna mention that- [00:07:00] Janet passed away before this trial could enroll its first patient. So it's sad, but I know her legacy lives on. She had appointed two co-PIs with her at Imperial [College London], Colin Bicknell and Anna Pouncey, who are carrying on this huge responsibility, and we are all grateful for her leadership for getting this huge international effort going. We hope to complete this study as rigorously and as well as she would've done.

Rachel Baker: Absolutely. Well, you wrote a comment for the Journal of Vascular Surgery with one of our residents, Pauline Berens.

Shipra Arya: Yes.

Rachel Baker: It's called Does One Size Fit All? And it really hit home to me because my father had an EVAR for his triple A when I was in college. And granted, he was a smoker. I am not. But when I asked my GP about screening, she kind of poo-pooed it, like, "Well, you're a woman, it's [00:08:00] fine." And I was just like, "Oh, okay." Um, so what are your thoughts on screening guidelines for women?

Shipra Arya: Uh, that's again, an excellent question, Rachel. I think we keep taking research from men and applying it to women and thinking that we're doing the right thing, and that was the idea behind this commentary that we really need to look at sex specific thresholds.

Women's aortas are smaller in general compared to men, and if we think about what is an aneurysm, it's a dilation above normal of the aorta. And so that threshold has to take into account the starting diameter. And so, if you apply five and a half centimeter criteria to men and women, in men that may be two, two and a half times bigger than their normal aorta.

In women, that could be three times bigger than their normal aorta or more. And as we know, [00:09:00] the bigger the diameter gets, the wall gets thinner and thinner, and that's what causes rupture. And that's why we think that if we apply the same criteria, women tend to present more with rupture, in elective settings for aortic aneurysm compared to men because we are treating them too late in their disease course.

And that's the whole premise of the WARRIORS trial, that we think the rupture risk of 4.2 centimeter aneurysm in women is equivalent to five and a half in men, and this is based on multiple observational studies, meta-analyses, modeling data.

You know, SVS and other international societies did recognize this even a decade ago that, you know, women should probably be fixed at a lower threshold. But there was no randomized clinical trial data, so it was more of a guesswork, "Okay, let's do five."

Rachel Baker: Anecdotal.

Shipra Arya: And while it is [00:10:00] based in observational evidence, it is not based in randomized evidence that: is five the correct threshold? and that needs to be tested, and that was the reason for this study.

In some countries, because five is not supported by a randomized trial, their guidelines still say five and a half for women. And so when we designed this trial, we proposed four to five and a half centimeter as the definition for small aneurysms in women. But there's a subgroup analyses we have planned.

We will look at four to five separately. It is also a randomization stratification. And then five to five and a half, my guess is we won't be able to randomize as many patients in the five to five and a half category here in the US. Mostly we will enroll women between four to five

Rachel Baker: Makes sense. I guess how does this impact insurance is my, is the thing that's coming out of my head-

Shipra Arya: Yeah

Rachel Baker: …in terms of like, you know, [00:11:00] when guidelines come out and they say, "Well, we're only gonna pay for a, you know, mammogram every two years after 40." Do these guidelines impact whether or not women can get, uh, you know, an EVAR for a AAA if it's under the guideline measurement?

Shipra Arya: Right. Because the guidelines don't have strong evidence, actually even right now throughout the country, insurers, because it's such a fatal disease, they leave the decision up to the discussion between surgeon and patient, because there is not

Rachel Baker: Thank goodness for that

Shipra Arya: yeah, that's good. And so, there are patients who have family history, or who are smokers, or who had rapid change, or who had some other abdominal pain that you can't rule out. So, we looked at this data in Vascular Quality Initiative, and there are a number of repairs happening across the country in women at that four to five centimeter threshold.

Rachel Baker: Hmm.

Shipra Arya: Because eventually it's a shared decision-making process, and surgeons kind of use these thresholds as guidance. [00:12:00] So we don't see an impediment in terms of insurance being an issue.

But of course, you know, we've had these discussions before. We've shown, um, that's why we looked at the data, observational data in detail through the national registry that yes, there is repair actually happening in these ranges right now, but we don't know if that's the right thing to do or wait till five.

So we are gonna test it, and so we're gonna do this in a pragmatic clinical trial, and that's the beauty of pragmatic trials. They compare two clinically acceptable strategies- which are currently being done, but compare them head-to-head to see which is the right way to go or improves the aneurysm-related mortality.

Rachel Baker: Absolutely. Well, so we'll put a link to the Warriors trial in our description so people can learn more. Yes. When are you expecting to start accepting patients into the trial?

Shipra Arya: So, we are actively [00:13:00] doing that right now. So, Stanford-

Rachel Baker: Yay!

Shipra Arya:... got its green light, like literally, a week ago to start enrolling patients.

Rachel Baker: Oh, amazing.

Shipra Arya:... Yes. Yay! Because AAA in women is not as common of a disease, we need 35 centers across the country.

Rachel Baker: Wow.

Shipra Arya: We are getting our first wave of sites up and running this month, and by August, we hope to have at least 25% of the sites up and running, and hopefully we have had our first patient enrolled by August.

So that's our goal.

Rachel Baker: Amazing. Hear that, women? It's here. Well, that sound means that it is time for our lightning round, and on each episode of Scrubcast, we ask each of our guests the same three questions, and the first one is: Who is a surgeon you admire and why?

Shipra Arya: So one of my biggest role models as a surgeon is Dr. Julie Freischlag. -

Rachel Baker: Oh, yeah.

Shipra Arya: ... you may know.

Rachel Baker: Quality human

Shipra Arya: Yeah. She's-- So she was the first female [00:14:00] president of the Society of Vascular Surgery. She was division chief. She was chair at Hopkins of Surgery. She was dean at UC Davis, and then CEO at Wake Forest, and she's recently retiring, but she's still full of joy and enthusiasm.

I am amazed by her energy, and that is what I admire most about her. Like, she leads with joy, you know? And it's about the people. It's about making sure that everybody around her thrives and has the best opportunities. So, um, that's what I admire most about her.

Rachel Baker: Love that. Love Julie Freischlag. The second question is: What is the best advice you have received in 10 words or fewer?

Shipra Arya: 10 words or fewer, wow. You know, this is something that Ron told me when I took on my first leadership role as section chief [00:15:00] here at the Palo Alto VA, and he said, "It's not about you anymore."

Rachel Baker: Hmm.

Shipra Arya: And I think I've taken that to heart, that when you step into a leadership role, you have to ensure that the people around you are doing well and are successful, and your success is measured by their success.

And I think I've tried to live up to that. It's hard sometimes, uh, because you come this far in your career focused on individual excellence, and suddenly when you go, get into a leadership role, you have to move your focus away and think about team excellence and how do you make everybody do well, and as a team, everybody becomes some greater than its parts.

So that's- Yeah ... kind of what I love about it.

Rachel Baker: We always say that surgery is a team sport.

Shipra Arya: Mm-hmm. Yeah, your name's on the chart, but you couldn't do this without all the different [00:16:00] people, you know, around you.

Rachel Baker: Absolutely. Yep. Final question, what is your preferred OR music?

Shipra Arya: Ooh. Uh, this is something that is, is a topic of discussion and comes up in my roasts a lot when the residents-

Rachel Baker: Controversial?

Shipra Arya: So, uh, I play a mix of Indian Bollywood-

Rachel Baker: Oh, yeah ...

Shipra Arya: Punjabi, and like pop music, especially female pop music, like Dua Lipa- Absolutely ... or Rihanna or, you know, um, so-

Rachel Baker: Yeah, keep the energy going.

Shipra Arya: Exactly. So I like this fast pace in my OR, and so I have this playlist that is infamous now that has all of these, and I keep adding more to it, uh, every time I hear something that I enjoy, but yeah, it's, uh, got this eclectic mix of, uh, Bollywood, Punjabi, English pop, and sometimes, you know, other, [00:17:00] inspirations that come along.

Rachel Baker: I feel like that might be like a vascular thing, that you're always looking for something that is in the, the range of like CPR beats per minute.

Shipra Arya: I think so. I think I should probably check some average beats per minute of my playlist.

Rachel Baker: It has been an absolute pleasure chatting with you. Uh, before we go, I want to ask one final question, and that is, what is next for Dr. Arya?

Shipra Arya: Ooh, I... That's a great question, Rachel. What is next is WARRIORS. I think that's the next big thing. I also have personal goals for the next few years. I'd like to focus on stability and growth in a meaningful way, be intentional about it, but try not to do too much.

You know, that's... As you know, I sometimes can't help myself, but, uh, trying to work with the people around me right now, work on the ideas that are currently gaining traction and just grow [00:18:00] vertically, meaningfully, uh, instead of trying to spread myself too thin. So that's the goal.

Rachel Baker: I love that. Well, I look forward to reading your publication on the PAUSE trial. I wish you the best of luck with WARRIORS. Thank you so much for coming on the show.

Shipra Arya: Thank you for having me, Rachel. It's been a pleasure, and I always enjoy chatting with you.

Rachel Baker: Thanks. And thank you to our listeners for tuning into this episode of Scrubcast. Until next time, stay sharp