Abstract: The proposed WARRIOR (Women’s Ischemia Trial to Reduce Events In Non-Obstructive CAD) trial is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) evaluating IMT vs. GMT in 4,422 symptomatic women with ischemia but no obstructive CAD. The hypothesis is that IMT will reduce MACE 20% vs. GMT. The primary outcomes are first occurrence of death, MI, Stroke/TIA, Hospitalization for chest pain or heart failure . Secondary outcomes include quality of life, health resource consumption, angina, CV death and primary outcome components. Follow-up will be 3-years using 50 sites: primarily VA and Active Duty Military Hospitals/Clinics and a PCORnet clinical data research network (OneFlorida Consortium).

Eligibility: Enrolled women will be clinically stable, with angina or equivalent symptoms of sufficient severity to seek, or have sought, referral for coronary angiography or coronary CT angiogram within the previous 2 years

Inclusion Criteria: 

• Signs and symptoms of suspected ischemia prompting referral for further evaluation by cardiac catheterization or coronary CT angiogram.
• Willing to provide written informed consent.
• Age ≥18 yrs.
• Non-obstructive CAD defined as <50% diameter reduction of a major epicardial vessel on invasive angiography within 2 yrs.

Exclusion Criteria: 

• History of noncompliance (with medical therapy, protocol, or follow-up).
• History of non-ischemic dilated or hypertrophic cardiomyopathy.
• Documented ACS within previous 30 days.
• LVEF <40%, NYHA HF class III-IV, or hospitalization for HFrEF within 180 days.
• Stroke within previous 180 ds. or intracranial hemorrhage at any time.
• End-stage renal disease, on dialysis, or estimated glomerular filtration rate (eGFR) <30 ml/min.
• Severe valvular disease or likely to require surgery/TVAR within 5 yrs.
• Life expectancy <3-yrs. due to non-cardiovascular comorbidity.
• Enrolled in a competing clinical trial.
• Prior intolerance to both an ACE-I and ARB.
• Pregnancy (all pre-menopausal females must have negative serum pregnancy test).