Women’s Ischemia Trial to Reduce Events in Non-Obstructive CAD - WARRIOR

Mar 29, 2025
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Author/Summarized by Author:
Dr. Carlos Dohse, MD
Summary Reviewer:
Fred M. Kusumoto, MD, FACC; Elizabeth H Dineen, DO, FACC
Trial Sponsor:
U.S. Department of Defense
Date Presented:
03/29/2025
Date Updated:
03/29/2025
Original Posted Date:
03/29/2025
References

Contribution To Literature:

The WARRIOR trial showed that among women with suspected INOCA, intensive medical therapy failed to significantly reduce the first occurrence of MACE vs. usual care at 5 years.

Description:

The goal of the trial was to determine whether intensive medical therapy vs. usual care would reduce first occurrence of major adverse cardiovascular events (MACE) in women with ischemia and nonobstructive coronary artery disease (INOCA) at 5-year follow-up.

Study Design

Symptomatic women with suspected INOCA at 71 U.S. medical centers were randomly assigned to receive intensive medical therapy (n=1,239), which consisted of a high-intensity statin, an angiotensin-converting enzyme (ACE) inhibitor, or angiotensin receptor blocker (ARB) at the maximally tolerated dose, and low-dose aspirin. The other half received usual care (n=1,237) dictated by the treating physician.

  • Total number of enrollees: 2,476
  • Duration of follow-up: 5 years
  • Mean patient age: 61.2 years
  • Percentage female: 100%

Inclusion criteria:

  • Clinically stable women with angina or angina equivalent
  • No obstructive coronary disease (coronary artery narrowing <50%)
  • Diagnosed by invasive coronary angiography or coronary CT angiography

Exclusion criteria:

  • Unstable angina, acute coronary syndrome, myocardial infarction (MI), PCI, or CABG
  • History of cardiomyopathy
  • Significant valvular or uncorrected congenital heart disease
  • HIV, hepatitis C, or liver disease
  • Estimated GFR <30 mL/min/1.73 m2
  • Expected survival <2 years
  • Noncompliance

Principal Findings:

Primary outcome: There was not a significant difference in the primary outcome in the intensive medical therapy (17.84%) vs. the usual care arms (16.17%) when it came to MACE (all-cause death, MI, stroke, or hospitalization for chest pain or heart failure) primarily driven by hospitalization for chest pain.

Secondary outcomes: There was not a significant difference in secondary outcomes, which included quality of life, time to return to “duty”/work, health care utilizations, angina, cardiovascular death, and individual primary outcomes over a 5-year follow-up.

Interpretation:

Though WARRIOR is a neutral trial showing no significant difference in MACE in the intensive medical therapy vs. usual care arms, patients with risk factors for coronary artery disease should have their risk factors evaluated and treated with high-intensity lipid-lowering agents and/or ACE inhibitor or ARB. Furthermore, this trial is evidence that additional studies are required in assessing the female population with INOCA, as they are considered a vulnerable population.

References:

Presented by Drs. Carl J. Pepine and Eileen Handberg at the American College of Cardiology Annual Scientific Session (ACC.25), Chicago, IL, March 29, 2025.

Clinical Topics: Atherosclerotic Disease (CAD/PAD), Stable Ischemic Heart Disease

Keywords: ACC25, ACC Annual Scientific Session, Coronary Artery Disease, Ischemic Heart Diseases, Women


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