Intensive Cardiovascular Medication for Coronary Artery Disease

(WARRIOR Trial)

Recruiting at 84 trial locations

Overseen By Chrisandra Shufelt, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Florida

Must be taking: Statins, ACE-I or ARB, Aspirin

Must not be taking: PCSK9

Disqualifiers: Cardiomyopathy, Stroke, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 years

2476 Participants Needed

Trial Summary

What is the purpose of this trial?

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 will 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). 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it involves intensive treatment with statins, ACE inhibitors (or ARBs), and aspirin, so you may need to adjust your current medications under the guidance of the trial doctors.

What data supports the effectiveness of aspirin in the treatment of coronary artery disease?

Aspirin is effective in reducing the risk of heart attacks and strokes in people at increased risk of cardiovascular events, lowering the risk by about 25%. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Aspirin, also known as acetylsalicylic acid (ASA), is commonly used for cardiovascular protection but can increase the risk of internal bleeding. While it can reduce the risk of heart attacks, it may not be suitable for everyone due to this bleeding risk, especially in people with diabetes or those using it for primary prevention. ^{6 7 8 9 10}

What makes this drug treatment for coronary artery disease unique?

This treatment combines ACE-I (lisinopril) or ARB (losartan) with aspirin and a high-dose potent statin, which is a unique combination aimed at intensively managing coronary artery disease by addressing blood pressure, reducing blood clot risk, and lowering cholesterol levels. The use of aspirin in this combination is notable for its role in reducing the risk of heart attacks and strokes, while the high-dose statin is particularly potent in lowering cholesterol, which is crucial for heart health. ^{1 11 12 13 14}

Research Team

Carl J Pepine, MD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for women with symptoms of ischemia (like chest pain) and non-obstructive coronary artery disease, which means their heart arteries are not severely narrowed. They should have had a cardiac evaluation within the last 5 years and be willing to consent to the study. Women who are pregnant or have serious heart conditions, severe kidney disease, or a recent stroke aren't eligible.

Inclusion Criteria

Willing to provide written informed consent

You have experienced symptoms that suggest a potential heart problem and have been referred for heart tests within the last 5 years.

You do not have significant blockages in your heart arteries.

Exclusion Criteria

You had a heart attack in the last 30 days.

History of noncompliance (with medical therapy, protocol, or follow-up)

You have a history of a certain heart condition called dilated or hypertrophic cardiomyopathy that is not caused by reduced blood flow to the heart.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive intensive statin/ACE-I (or ARB)/aspirin treatment or usual care

3 years

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Ongoing monitoring

Treatment Details

Interventions

• ACE-I (lisinopril) or ARB (losartan)
• Aspirin
• High dose potent statin
• Lifestyle Counseling
• Quality of Life Questionnaires

Trial Overview The WARRIOR trial tests whether intensive medical treatment with statins, ACE inhibitors (or ARBs), and aspirin can reduce major adverse coronary events in women compared to usual care. It's a randomized study where outcomes like heart attacks and quality of life will be tracked over three years.

Participant Groups

Group I: Intensive Medical Treatment (IMT) Experimental Treatment 5 Interventions

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.

Group II: Usual Care (UC) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study of 444 patients over an average of 48 months, high-dose aspirin (650 mg twice daily) was found to be poorly tolerated, with 16% of patients stopping the medication entirely due to adverse effects.

Common adverse reactions included heartburn or stomach pain (42% of patients), nausea or vomiting, and bloody stools, indicating that even low-dose enteric-coated aspirin can lead to significant gastrointestinal issues in patients, despite screening for intolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. The VA Cooperative Asymptomatic Carotid Artery Stenosis Study Group. Krupski, WC., Weiss, DG., Rapp, JH., et al.[2019]

Aspirin at a dose of approximately 300 mg/day can significantly reduce the risk of myocardial infarction (MI) by about 50% in patients with moderate to high cardiovascular risk, and lower doses (150 mg/day) can decrease mortality by 23% during the acute phase of MI.

Antiplatelet agents, including aspirin and ticlopidine, are effective in preventing thrombosis after coronary surgeries and in managing conditions like cerebral ischemic accidents, highlighting their importance in both primary and secondary prevention strategies for cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors, interventions and therapeutic agents in the prevention of atherosclerosis-related ischaemic diseases. Verstraete, M.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

[Aspirin and cerebral ischemic accidents]. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Comparison of the effectiveness and safety of 2 aspirin doses in secondary prevention of cardiovascular outcomes in patients with chronic kidney disease: A subgroup analysis of ADAPTABLE. [2023]

3. Poland pubmed.ncbi.nlm.nih.gov

Factors responsible for "aspirin resistance" - can we identify them? [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. The VA Cooperative Asymptomatic Carotid Artery Stenosis Study Group. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the ASA low-response prevalence in CVD, CAD and PAD. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Aspirin: Bitter pill or miracle drug? [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

The impact of upper gastrointestinal symptoms on nonadherence to, and discontinuation of, low-dose acetylsalicylic acid in patients with cardiovascular risk. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

Possible interaction between aspirin and ACE inhibitors: update on unresolved controversy. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Primary Prevention of Cardiovascular Events with Aspirin: Toward More Harm than Benefit-A Systematic Review and Meta-Analysis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Survey of cardiac surgeons' perceptions of the addition of ASA to warfarin for patients with mechanical heart valves. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Rapid oral challenge-desensitization for patients with aspirin-related urticaria-angioedema. [2013]

13. England pubmed.ncbi.nlm.nih.gov

Aspirin rechallenge in an adult patient previously diagnosed with Reye syndrome. [2021]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Risk factors, interventions and therapeutic agents in the prevention of atherosclerosis-related ischaemic diseases. [2018]