WARRIOR Trial Finds No Added Benefit From Intensive Medical Therapy in Women With INOCA

The long-anticipated WARRIOR trial sought to answer a big question: Can intensive medical therapy (IMT) reduce cardiovascular events in women with ischemia with nonobstructive coronary arteries (INOCA)? After five years, the verdict is in—and it's not what many had hoped for.

Trial Snapshot

• Study Design: Randomized, controlled, pragmatic trial

• Enrollment: 2,476 women (target: 4,476)

• Follow-up: 5 years

• Sites: 71 U.S. medical centers

• Population: Women with symptoms of ischemia but no obstructive coronary artery disease

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Inclusion Criteria

Women were eligible for enrollment if they met all of the following:

• Adult women aged 18 or older

• Documented symptoms suggestive of myocardial ischemia (e.g., chest pain, dyspnea)

• Nonobstructive coronary arteries (<50% stenosis) confirmed by:

  • Coronary computed tomography angiography (CCTA) or

  • Invasive coronary angiography

• Willing and able to comply with long-term follow-up and treatment

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Exclusion Criteria

Patients were excluded if they had any of the following:

• Obstructive coronary artery disease (≥50% stenosis)

• History of myocardial infarction, coronary revascularization, or stroke

• Left ventricular ejection fraction <40%

• Life expectancy <5 years from non-cardiac illness

• Contraindications or known intolerance to statins, ACE inhibitors, ARBs, or aspirin

• Active pregnancy or breastfeeding

A Trial Caught in a Storm

The trial was hit hard by the COVID-19 pandemic, enrolling just 55% of its planned 4,476 participants. Its pragmatic design—while realistic—blurred the lines between study groups. About half of the patients in the usual care group ended up receiving medications that were meant to be exclusive to the IMT group, like statins, ACE inhibitors, and ARBs.

Despite the hurdles, researchers pushed forward, enrolling 2,476 women (average age 64 years, 89% white) across 71 US medical centers. Patients were randomized to receive:

• Intensive Medical Therapy (IMT):

  • High-intensity statin

  • ACE inhibitor or ARB at maximally tolerated dose

  • Low-dose aspirin

• Usual Care:

  • Treatment at the physician’s discretion

Yet, when the dust settled, no significant difference was found between the groups.

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The Hard Numbers

After 5 years, the composite risk of all-cause death, myocardial infarction (MI), stroke, hospitalization for angina, or heart failure showed:

• Hazard Ratio (HR): 1.13

• 95% Confidence Interval (CI): 0.94–1.37

• 83.4% of events were hospitalizations for chest pain

The quality-of-life scores and individual components of MACE (major adverse cardiovascular events) also showed no significant difference.

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A Nuanced Picture

Though labeled as a “neutral” study, experts caution against taking this as a signal to abandon treatments like statins, ACE inhibitors, or ARBs—especially in women with cardiovascular risk factors.

The fact that so many women in the usual care group were already on these medications points to an improvement in standard care. But it also makes it harder to prove the added value of IMT.

The field has long struggled with variation in treatment for INOCA, and clinical guidelines remain unclear. Previous studies, like CorMiCa, hinted at benefits from antianginal therapy, but real-world practice remains scattered.

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A Call for Continued Research

Even in its neutral outcome, WARRIOR was hailed as a milestone in the understudied field of women’s heart health. Researchers emphasized the need for:

• More focused trials

• Standardized treatment protocols

• Biomarker and AI-based imaging studies

• Deeper analysis of medication tolerability

There’s also a psychological dimension at play. Many women with INOCA, after being told there's "nothing wrong," may question the need for long-term treatment, especially when symptoms fade. Clinicians must navigate complex care conversations in a field riddled with uncertainty.

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Take-Home Points

• WARRIOR trial found no significant difference in cardiovascular outcomes between IMT and usual care in women with INOCA.

• COVID-19 and pragmatic trial design contributed to limitations, including treatment crossover.

• A high proportion of usual care patients were already on cardioprotective medications, likely blunting the study’s ability to detect a benefit.

• Quality-of-life and hospitalization rates for chest pain remained similar across both arms.

• The trial highlights the urgent need for continued research, clearer treatment strategies, and better diagnostic tools in women’s cardiovascular health.

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Even though WARRIOR didn’t deliver the clarity everyone hoped for, it shines a light on the grey zones of cardiology and reminds us that science marches forward even through the fog.