A Phase 4 interventional study of High dose potent statin and ACE-I (lisinopril) or ARB (losartan) in Coronary Artery Disease, sponsored by Cedars-Sinai Medical Center. Active, not recruiting at 81 sites in 2 countries. Open to female participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-10-30.
Sponsored by Cedars-Sinai Medical Center · Phase 4, Interventional, and Treatment
The Ischemia-IMT (Ischemia-Intensive Medical Treatment Reduces Events in Women with Non-Obstructive CAD), subtitle: Women's Ischemia Trial to Reduce Events in Non-Obstructive CAD (WARRIOR) trial is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) evaluating intensive statin/ACE-I (or ARB)/aspirin treatment (IMT) vs. usual care (UC) in 4,422 symptomatic women patients with symptoms and/or signs of ischemia but no obstructive CAD. The hypothesis is that IMT will reduce major adverse coronary events (MACE) 20% vs. UC. The primary outcome is first occurrence of MACE as death, nonfatal MI, nonfatal stroke/transient ischemic attack (TIA) or hospitalization for heart failure or angina. Secondary outcomes include quality of life, time to "return to duty"/work, health resource consumption, angina, cardiovascular (CV) death and primary outcome components. Events will be adjudicated by an experienced Clinical Events Committee (CEC). Follow-up was planned to be 3-years using 50 sites: primarily VA and Active Duty Military Hospitals/Clinics and a National Patient-Centered Clinical Research Network (PCORnet) clinical data research network (CDRN)(OneFlorida Consortium). The number of sites were increased and follow up was modified to continue until the last patient enrolled was followed until trial follow up was completed. Recruitment was complete January 6, 2024.
This study is being conducted to determine whether intensive medication treatment to modify risk factors and vascular function in women patients with coronary arteries showing no flow limit obstruction but with cardiac symptoms (i.e., chest pain, shortness of breath) will reduce the patient's likelihood of dying, having a heart attack, stroke/TIA or being hospitalized for cardiac reasons. The results will provide evidence data necessary to inform future guidelines regarding how best to treat this growing population of patients, and ultimately improve the patient's cardiac health and quality of life and reduce health-care costs.
WARRIOR trial is a multi-site, PROBE design, that will evaluate an intensive statin/ACE-I (or ARB)/aspirin treatment strategy (IMT) vs. primary prevention risk factor therapy treatment strategy (UC) in 4,422 symptomatic (chronic angina or equivalent) women with non-obstructive CAD (\<50% diameter narrowing).
There will be \~80 US sites, including VA/ military and OneFlorida CDRN sites, with a proven record in prior trials. The investigators will use web-based, real-time data entry, and management University of Florida Data Management System (UFDMS) for site selection, screening, participant eligibility confirmation, enrollment, and randomization. Participants will be recruited from screened women with symptoms suspected to be ischemic with non-obstructive CAD by invasive coronary angiogram or CT angiogram. The high dose statin (atorvastatin or rosuvastatin) and ACE-I (lisinopril) [or ARB (losartan)] are generic commonly used medications previously demonstrated effective for improving angina, stress testing, myocardial perfusion and coronary microvascular flow reserve in small size trials in this population. Additionally, aspirin will also be recommended to IMT participants without contraindications or excess bleeding risk, however aspirin will not be provided by the study. Both the groups will also receive Lifestyle Counseling (PACE Assessment), and the same visit schedule and "face-time" with site staff to reduce bias. Events will be adjudicated by the Clinical Events Committee (CEC), according to objective criteria and masked to treatment assignment clues.
4,857 studies on the registry are indexed under Coronary Artery Disease; 890 are open to participants now.
This study's enrollment of 2,476 is above the median of 124 across 3,006 interventional studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →Cedars-Sinai Medical Center is the lead sponsor of 456 studies on the registry; 107 are open to participants now.
Of its 65 completed or terminated interventional studies of FDA-regulated products, 49 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The IMT-assigned women will receive high dose potent statin, and moderate dose of an ACE-I (lisinopril) or ARB (losartan). Aspirin will also be recommended to IMT women without contraindications or bleeding risk. This group will also receive Lifestyle Counseling (PACE Assessment), Quality of Life questionnaires, and the same visit schedule and "face-time" with site staff to reduce bias.
Drug: High dose potent statin · Drug: ACE-I (lisinopril) or ARB (losartan) · Drug: Aspirin 81 enteric coated tablet daily · Behavioral: Lifestyle Counseling · Behavioral: Quality of Life Questionnaires
The UC-assigned women will maintain standard of care. This group will also receive Lifestyle Counseling (PACE Assessment), Quality of Life questionnaires, and the same visit schedule and "face-time" with site staff to reduce bias.
Behavioral: Quality of Life Questionnaires
The IMT-assigned women will receive high-dose, potent statin (atorvastatin 40-80 mg/d or rosuvastatin 20-40mg) class of lipid-lowering medications.
Also known as: atorvastatin or rosuvastatin
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are widely prescribed for primary hypertension.
Also known as: ACE-I or ARB
Will be recommended to IMT women without contraindications or bleeding risk.
Also known as: Aspirin
The PACE Lifestyle Assessment Intervention which is a program to assist with smoking cessation, weight loss, and exercise.
Also known as: PACE Lifestyle Intervention
Quality of Life Questionnaires will be obtained.
Also known as: QOL
The primary outcome is MACE, defined as first occurrence of all-cause death, non-fatal MI, non-fatal stroke, or hospitalization for angina or HF.
All-cause death will be used 1) CV death is insensitive in this population with non-obstructive CAD since death is less likely attributed to CV causes when no obstructive CAD is present; 2) all-cause death is resistant to ascertainment bias in this unblinded trial. CV death will be defined broadly to include both definite CV death and possible CV death (all deaths except those with definite non-CV cause, e.g., cancer, witnessed trauma and homicide). The MI definition follows universal criteria for Types 1-5 MI events. Stroke/TIA definition is new onset neurological defect of central origin confirmed by brain imaging (CT or MRI) evidence of cerebral infarction or intracerebral hemorrhage. Hospitalization for angina- Any hospitalization for angina, plus unstable angina or ACS. Hospitalization for Heart Failure -required established objective criteria for heart failure. All MACE events are adjudicated by a blinded Clinical Endpoint Committee
Time frame: Within 5 years
Components of MACE
The analysis will be repeated for the following combinations of MACE events (1) composite outcome of CV-death, non-fatal MI, or non-fatal stroke/TIA; (2) composite outcome CV-death, non-fatal MI, resuscitated cardiac arrest, or hospitalization for angina or heart failure; (3) all-cause mortality; (4) CV-death (5) total MI \[fatal plus non-fatal\]; (6) resuscitated cardiac arrest; (7) hospitalization for angina; (8) hospitalization for HF; (9) total stroke/TIA \[fatal plus non- fatal\]; (10) composite outcome of CV-death, non-fatal MI, stroke/TIA, resuscitated cardiac arrest, or hospitalization for angina or heart failure.
Time frame: Within 5 years
Composite hierarchical MACE endpoint
The comparison of randomized treatment strategies for composite hierarchical endpoint will be conducted using win statistics (WS), including the win ratio (WR), win odds (WO), will be computed to compare two groups based on hierarchical order of clinical importance as follows: 1) all cause death within 5 yrs, 2) stroke within 5 yrs, 3) MI within 5 yrs, 4) number of hospitalization within 5 yrs, 5) first hospitalization for heart failure or chest pain within 5 yrs, and 6) average of SAQ7 at 6 months and 1-year. The WR method compares each patient in the intervention group with every patient in the control group, and the magnitude of the effect is computed as the ratio of the total number of pairwise "wins" to "losses" considering the predefined hierarchy of the outcomes. Since the WR does not account for ties that the WO will also be computed. The benefit of the IMT arm is indicated by an estimate of WS/WO test statistic with their respective 95% confidence intervals greater than 1.
Time frame: Within 5 years
Seattle Angina Questionnaire (SAQ).
QoL comparisons will adhere to the ITT principle. We will examine changes over time from baseline and identify the major determinants of those changes using regression analysis. Questionnaires, such as the SAQ scores, at each time point will be analyzed using linear mixed models with correlation within subjects over time. In case the outcome residuals do not have a normal distribution, a transformation will be considered (e.g. log, Box-Cox). Interaction of group and time effects will be examined to assess for different time trends between groups.
Time frame: Study entry and every six months until end of follow up (up to 72 months)
EQ-5D-3L
Evaluated over time by group.
Time frame: Study entry and every six months until end of follow up (up to 72 months)
Duke Activity Status Inventory (DASI)
DASI as assessed over time by group.
Time frame: Study entry and every six months until end of follow up (up to 72 months)
Modified Morisky Medicine Scale Take your medication
Measure of medication compliance between groups over time.
Time frame: Study entry and every six months until end of follow up (up to 72 months)
PACE (Programs of All-Inclusive Care for the Elderly).
Assessment of healthy lifestyle intervention between groups over time.
Time frame: Study entry and every six months until end of follow up (up to 72 months)
PCL-5 (Screening for PTSD).
Screening for PTSD over time between groups
Time frame: Study entry and every six months until end of follow up (up to 72 months)
Health care utilization and cost effectiveness
Comparing health care resource utilization across time between groups.
Time frame: Study entry and every six months until end of follow up (up to 72 months)
GAD 7
Assessment of general anxiety over time between groups
Time frame: Study entry and every six months until end of follow up (up to 72 months)
PHQ 8
Assessment of depression over time between groups
Time frame: Study entry and every six months until end of follow up (up to 72 months)
MACE and Quality of Life outcomes will also be stratified by enrollment assessment of non-obstructive CAD using noninvasive CCTA vs invasive coronary angiography
MACE is first occurrence of all cause death, non fatal MI, non fatal stroke or TIA, hospitalization for heart failure, hospitalization for chest pain/angina. Quality of life is being assessed using Seattle Angina Questionnaire, SAQ7 and all of the SAQ domains, PTSD is being assessed using the PCL5, functional capacity is being assessed using the Duke Activity Status Index, EQ-5D-3L, Depression is being assessed using the PHQ-8 and anxiety using the GAD-7
Time frame: Within 5 years
An analysis of MACE with repeated events considering the number of previous events as a time-dependent covariate will be performed
Using Andersen-Gill model with frailty to describe the repeated events: all-cause death, non-fatal MI, non-fatal stroke/TIA, or hospitalization for either angina or heart failure. Definitions of repeated events include 30 days between a documented MI and death as a standard definition for "Fatal MI" and \>48hrs was a standard for exacerbation of ischemia (chest pain or ECG changes of ischemia) to call it a "new event" (e.g., either an MI, HF, or another exacerbation of ischemia).
Time frame: Within 5 years
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Feb 2018 to primary completion in May 2024, 75 months.
Of 180 non-industry phase 4 interventional studies under Coronary Artery Disease, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 59. This study's 75 months is above that.
Counting every sponsor, half of 193 studies reached it within 35 months; a quarter within 19 and three quarters within 58.
Since we started tracking on Sep 25, 2026, the dates moved once, on Oct 30, 2026: primary completion Sep 2026 → May 2024 and completion Sep 2026 → Apr 2027.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Lisinopril · Aspirin