Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR): a randomised controlled trial

Clinical Snapshot

Key Findings

• P Value: p=0.20

• Effect Size: HR 1.13 favouring usual care (non-significant trend toward harm with IMT)

• Primary Outcome: No significant difference in composite MACE between intensive medical treatment and usual care

• Nnt Or Sensitivity: No NNT calculable due to lack of benefit; 421 total events (221 IMT vs 200 usual care)

• Confidence Interval: 95% CI 0.94 to 1.37

Clinical Application

Intervention components (statins, ACE inhibitors/ARBs, aspirin) are readily available and commonly prescribed in Australian practice All study medications are PBS-subsidised in Australia. Findings challenge routine intensive medical therapy in this population, supporting individualised approach consistent with current RACGP and Cardiac Society guidelines Women with chest pain and angiographically normal coronary arteries, particularly relevant given high prevalence in Australian cardiology practice

Abstract

IMPORTANCE: Women with angina due to suspected ischaemia referred for coronary angiography often have no obstructive coronary artery disease (ANOCA/INOCA). OBJECTIVE: To determine if intensive medical treatment (IMT) reduces major ischaemic events (major adverse cardiovascular event, MACE) among women with suspected ANOCA/INOCA. DESIGN: Randomised, prospective, blinded-outcomes evaluation. SETTING: 71 sites in the USA. PARTICIPANTS: 2476 women with suspected ANOCA/INOCA. INTERVENTIONS: IMT-high intensity statin, ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) and aspirin versus usual care (UC). MAIN OUTCOMES AND MEASURES: Primary: all cause death, myocardial infarction, stroke/transient ischaemic attack, hospitalisation for angina or heart failure (MACE). Secondary: components of the primary, quality of life and win ratio. RESULTS: Recruitment was lower than planned (n=2476), yielding an aged population (mean, 64 years) with well-controlled blood pressure and low-density lipoprotein cholesterol at baseline, and relatively high rates of statin and ACEI/ARB use. At 2.5 years, 421 events occurred (221 in IMT, 200 in UC) with no difference in the primary outcome (HR=1.13 (95% CI 0.94 to 1.37) for IMT vs UC, p=0.20) or secondary outcomes. Hospitalisations for angina were the dominant contributor to MACE. Sensitivity analysis of contamination provided an estimated HR for IMT versus UC of 0.74 95% CI (0.352 to 1.558), p=0.43. CONCLUSIONS AND RELEVANCE: Among women with suspected ANOCA/INOCA, outcomes were dominated by chest pain and IMT did not improve outcomes, although limited power precludes concluding that it may not be helpful. The findings support the need for more investigation in this population with high burden of angina hospitalisation, health resource consumption and poor quality of life. TRIAL REGISTRATION NUMBER: NCT03417388.

References

1. 1.Pepine, C. J., Handberg, E., Cooper-DeHoff, R., Cook-Wiens, G., Diniz, M. A., Frayne, S., Lo, M. C., Smith, S. M., Harris, B., Wei, J., Chaitman, B. R., Spertus, J. A., Berry, C., Weintraub, W., & Bairey Merz, C. N. (2026). Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR): a randomised controlled trial. Open Heart, Article openhrt-2026-004115. https://doi.org/10.1136/openhrt-2026-004115