Keep Fighting INOCA After Neutral WARRIOR Trial

Drs O’Donoghue, Handberg, and Bairey-Merz discuss the WARRIOR trial of intensive medical therapy in women with nonobstructive symptomatic CAD, presented at the ACC 2025 Scientific Session.
https://www.medscape.com/viewarticle/keep-fighting-inoca-after-neutral-warrior-trial-2025a10007uf?src=soc_yt

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Michelle L. O’Donoghue, MD, MPH: Hi. This is Dr Michelle O'Donoghue, reporting for Medscape. I'm here at the 2025 American College of Cardiology Scientific Session in Chicago to talk about women's heart health and, importantly, the results of the WARRIOR trial. Joining me today are Dr Noel Bairey-Merz, who is from the Barbra Streisand Women's Heart Center at Cedars-Sinai, as well as Eileen Handberg, who is at the University of Florida and is director of cardiovascular research there. Thank you both for joining me.

Understanding INOCA
Taking a step back before we talk about WARRIOR specifically, let's think about where we are in terms of the management of women who have different types of heart disease. We have a well-trodden path for management of coronary disease that is visible to the eye on epicardial imaging, but we have been running into challenges in terms of understanding how to best manage patients, both women and men, who have evidence of ischemia but no clear epicardial disease, at least to the naked eye. What are your thoughts on where the gap has been in our knowledge base, and whether there are differences between women and men in that regard?

C. Noel Bairey-Merz, MD: Thanks for asking. The WISE study, but many studies across the globe now, demonstrate this is a burgeoning epidemic. It's probably about half of ischemic heart disease in women. And men are closely in pursuit, with many angiograms now in the VA CART program demonstrating that almost half also lack obstructive coronary disease, despite evidence of ischemia. So this is a big problem.

We've been studying small-vessel dysfunction for 25-plus years. We did some pharmacologic PROBE trials suggesting that high-intensity statins and a maximally tolerated angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) could be effective treatment because of the often concomitant, nonobstructive coronary disease, as you alluded to. That was the rationale for this, because most of these patients are not treated. Clinical guidelines are lacking; they’re given reassurance, “we’ll treat the risk factors, there’s probably nothing to worry about.”

O’Donoghue: You make such an important point that for all too long, we've been patting people on the back well after they have a coronary angiogram that doesn't demonstrate any clear obstructive coronary disease, but yet we know that ischemia with no obstructive coronary arteries (INOCA) is associated with worse outcomes. It has been a real challenge to know how best to try to reduce risk once that diagnosis is made.

Pivoting to the WARRIOR trial, what was the idea behind the design there?

The WARRIOR Trial
Eileen Handberg, PhD: We wanted to test the question that Noel raised about what's optimal treatment for this population of women. At specialized centers, who've been seeing these women for the past 25 years, we see recurrent hospitalizations use of healthcare resources and have had success with use of high-intensity statin and moderate-dose ACEI or ARB therapy, but never in a randomized trial to prove that the way we manage is correct.

The trial we designed to be pragmatic and real-world, randomizing participants to a high-intensity statin, a moderate-dose ACEI or ARB, and baby aspirin compared with usual care. This was funded by the Department of Defense because about 20% of the military are women. They're trying to get ahead of the curve. They provide care for a lot of retirees and dependents, so they agreed to answer this question, because it could be that therapy is good or not good, but you have to do the trial to get that answer.

Transcript in its entirety can be found by clicking here: https://www.medscape.com/viewarticle/keep-fighting-inoca-after-neutral-warrior-trial-2025a10007uf?src=soc_yt