WARRIOR Underscores Burden of Nonobstructive Angina in Women

In ladies folk with indicators of ischemia but no obstructive coronary artery disease (OCAD), intensive scientific therapy did not lower the first occurrence of a first-rate cardiovascular event in the WARRIOR trial, but the trial became underpowered to inform a definitive outcome.

“That is a neutral trial and might perchance per chance simply not be regarded as a adversarial trial,” acknowledged study investigator Eileen Handberg, PhD, professor of tablets at the College of Florida in Orlando. “We had insufficient adherence and energy to test the major hypothesis.”

“These outcomes might perchance per chance also simply quiet not be interpreted as endorsing discontinuation of statins or antihypertensive drugs amongst ladies folk with cardiovascular threat factors,” she outlined all the arrangement thru her presentation of the outcomes at the American Faculty of Cardiology Scientific Session 2025 in Chicago.

The WARRIOR trial is main because it’s the first substantial, randomized study to be conducted in a population of girls folk who expertise indicators and indicators of ischemia but who were found not to have an obstruction in their coronary arteries, a condition identified as ischemia with no OCAD, she outlined.

That is a substantial population. Within the United States, an estimated 4-5 million ladies folk search for scientific advice after reporting indicators of cardiac ischemia, akin to chest effort, shortness of breath, and dizziness excessive ample to fill review with coronary CT angiogram or invasive coronary angiography. About half of of those ladies folk are found not to have OCAD.

Hospitalizations for Angina

“Our outcomes show a high affected person and doctor burden related with this condition, with a extremely high payment of recurrent angina hospitalizations. These ladies folk are the employ of somewhat lots of healthcare resources. They’ve hypertension and elevated ldl cholesterol that must be aggressively handled,” Handberg acknowledged. 

“Now we must hear to these ladies folk. Now we must assign away with the bias of the effort being a chunk of bit assorted, and we might perchance per chance also simply quiet not push aside their indicators and jabber they assign not need put collectively-up. They variety need put collectively-up,” she added. “These ladies folk have comorbidities, and so that they might perchance simply quiet be getting cheap threat-slash payment solutions. The ladies folk in this study were somewhat effectively handled at baseline, which is a upright ticket that we’re shifting in that route, but there might perchance be somewhat lots of need for enchancment.”

The WARRIOR trial assessed 2476 ladies folk (real looking age, 60 years) at 71 scientific companies and products in the United States. About half of the trial population had obesity and most had assorted cardiovascular threat factors, akin to hypertension, high low-density-lipoprotein ldl cholesterol (LDL-C), or a family history of coronary disease.

Patients were randomly assigned to receive intensive scientific therapy, which consisted of a high-intensity statin, an ACE inhibitor or angiotensin receptor blocker at the maximally tolerated dose, and low-dose aspirin. The assorted half of got long-established care, which arrangement that choices about prescriptions and various therapies were left to the discretion of the treating doctor.

After 5 years of put collectively-up, there became no main distinction between the two teams in the major endpoint, which became a composite of the first occurrence of demise, myocardial infarction, stroke or transient ischemic attack, or hospitalization for heart failure or angina. 

About 16% of sufferers in both teams skilled an event in the composite endpoint at 5 years. There were no main differences between intensive scientific therapy and long-established love any of the secondary endpoints or subgroups analyzed.

COVID Pandemic Affected Recruitment

The trial became underpowered because the team had effort recruiting sufferers all the arrangement thru the COVID-19 pandemic.

“The trial had to shut for six months when the nation shut down, and it tremendously impacted our capability to assign sites active, with crew and sufferers not being in a affirm to achieve back to healthcare companies and products. And when trials quit, they lose inertia, after which you must always rebuild the fervour,” Handberg outlined. This resulted in the trial falling effectively looking its plot of enrolling 4422 individuals.

There became also a lower diploma of angina at baseline than anticipated, which reduced the capability to enhance angina indicators and related quality of life. And sufferers in the management community were somewhat effectively handled at baseline, with 70% taking statins, about half of taking an ACE inhibitor or angiotensin receptor blocker, and 40% taking a beta blocker.

As effectively as, the begin-ticket plot doubtless resulted in increased-than-anticipated trial “contamination,” which occurs when sufferers are not handled in keeping with the assigned strategy.

This became anticipated to a diploma. It became assumed that sufferers assigned to long-established care would be taking some intensive drugs, and that sufferers assigned to intensive scientific therapy would not rob about a of their assigned drugs. Alternatively, this came about more once quickly than anticipated.

“Within the muse, 16% of long-established-care sufferers were receiving intensive drugs and 52% of the intensive community weren’t adherent to the assigned strategy,” Handberg reported. Plus, “adherence in both fingers declined further over time.”

Alternatively, in a sensitivity diagnosis that took this into narrative, the estimated hazard ratio for the major endpoint became 0.74 for intensive treatment in of us that were compliant with assigned therapies, suggesting a 25% slash payment in cardiovascular events, which is “potentially supportive of an attain for intensive therapy,” she acknowledged.

The slash payment in LDL-C became modest but vastly lower in sufferers assigned to intensive scientific therapy than to long-established care, with a time-averaged distinction of seven.6 mg/dL, but there became no detectable distinction in blood stress management between teams.

Necessary Messages

“We have a tendency to mediate if a trial doesn’t meet its endpoint, or not it will not be crucial, and that we can’t be taught from it, but that couldn’t be more mistaken in this surroundings,” acknowledged Pamela Douglas, MD, professor of research in cardiovascular diseases at Duke College in Durham, North Carolina. “Now we have heard how crucial this population is, how long-established this disease is, how minute all of us to find out about it, and how high the burden is.”

At some level of the route of the trial, 17% of sufferers required hospitalization. “That’s higher than one in six, an incredibly informative figure,” she acknowledged.

The study plot became “ambitious,” Douglas acknowledged. “This pragmatic plot — which is what wishes to happen going ahead — might perchance per chance also simply quiet not be at a loss for words with a pure efficacy trial, where issues are tightly controlled, and the intervention is designed and delivered seamlessly but at sizable tag to individuals and to review investigators.” 

Several ancillary analysis are underway to evaluate, more closely, the coronary anatomy of the individuals, and blood samples will doubtless be analyzed to explore mechanisms of disease and that that it’s most likely you’ll also imagine novel therapeutic targets, Handberg reported.

“These ongoing substudies will proceed to make a contribution to enhance our working out of this rising affected person population and its symptom burden,” she added.

The WARRIOR study became an fulfillment, in that it became the ideally suited trial ever in this community of girls folk who are not effectively understood, acknowledged Kim Eagle, MD, from the College of Michigan College of Public Smartly being in Ann Arbor.

“The physiology of this condition continues to mystify us. Is it vascular reactivity? Is it lipids? Is it spasm? Is it irritation? A pair of of those nuances will presumably attain from the substudies of this trial,” he added.

The WARRIOR trial became funded by the US Division of Protection. Handberg, Douglas, and Eagle myth no relevant financial disclosures.