Intensive Cardiovascular Medication for Coronary Artery Disease

(WARRIOR Trial)

No longer recruiting at 85 trial locations

Overseen By Edlira Maska

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if intensive medication treatment can help women with heart symptoms and non-obstructive coronary artery disease (where arteries aren't fully blocked) avoid major heart issues like heart attacks or strokes. Participants will receive either intensive treatment with medications such as ACE inhibitors (like lisinopril), ARBs (like losartan), statins, and aspirin, or continue with their usual care. Women who frequently experience chest pain or shortness of breath related to heart issues might be suitable candidates. The goal is to gather evidence to improve future care guidelines and enhance heart health and quality of life for this group.

As a Phase 4 trial, the treatment is already FDA-approved and proven effective. This research aims to understand how it benefits more patients, offering an opportunity to contribute to the improvement of heart health care.

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 is the safety track record for these treatments?

Research shows that the treatments in this trial are generally well-tolerated. ACE inhibitors, such as lisinopril, and ARBs, like losartan, are commonly used for heart conditions. Studies indicate they do not significantly increase the risk of heart attacks or strokes compared to each other and are considered safe for long-term heart health management.

Aspirin is also part of the treatment plan and is known to help reduce heart attacks and strokes. However, aspirin can increase the risk of bleeding, which is particularly important for individuals with bleeding disorders to consider.

High-dose statins are another treatment option in this trial. These statins effectively lower bad cholesterol (LDL) by more than 50%. While generally safe, there is a very low risk of muscle injury and liver issues. The chance of serious muscle problems is less than 0.1%, and for liver problems, it’s about 0.001%.

Overall, the treatments have a strong safety record based on past research. However, individual risks can vary, so participants should discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the intensive cardiovascular medication regimen for coronary artery disease because it combines a high dose potent statin with a moderate dose of either an ACE inhibitor (like lisinopril) or an ARB (like losartan), plus aspirin for those without bleeding risks. This comprehensive approach not only aims to lower cholesterol levels more effectively but also addresses blood pressure control and clot prevention all at once. Unlike many standard treatments that might focus on just one aspect of heart health, this regimen offers a more holistic strategy. This could potentially lead to better overall outcomes for patients with coronary artery disease.

What evidence suggests that this trial's treatments could be effective for coronary artery disease?

In this trial, participants in the Intensive Medical Treatment (IMT) arm will receive a combination of high-dose statins, ACE inhibitors (such as lisinopril) or ARBs (such as losartan), and aspirin. Research has shown promising benefits for heart health with this combination. Studies indicate that high-dose statins can lower bad cholesterol (LDL) by over 50% and may help reduce artery blockages. ACE inhibitors have been found to decrease major heart-related events by 14%. Although the best dose of aspirin remains debated, it is commonly used to prevent heart attacks and strokes. The trial aims to determine if these treatments together can further reduce the risk of serious heart problems in women with coronary symptoms but no major blockages. Participants in the Usual Care (UC) arm will maintain their standard of care. ^{1 2 3 5 6}

Who Is on the Research Team?

Carl J Pepine, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6486121/

Angiotensin converting enzyme (ACE) inhibitors versus ... Our analyses found no evidence of a difference in total mortality or cardiovascular outcomes for ARBs as compared with ACE inhibitors, while ARBs caused ...

2. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.16667

Comparative First-Line Effectiveness and Safety of ACE ... We found no statistically significant difference in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11 for ACE versus ARB ...

3. academic.oup.com academic.oup.com/ehjcvp/advance-article/doi/10.1093/ehjcvp/pvaf051/8241184

Long-term effectiveness of ACE inhibitors or angiotensin ... In summary, we estimated that ACEi/ARBs had little or no effect on the 5-year risk of death, myocardial infarction, and heart failure among low- ...

4. link.springer.com link.springer.com/article/10.1007/s40119-024-00381-6

ACE Inhibitors and Angiotensin Receptor Blockers for the ... Treatment with an ACEi also reduced the rate of major cardiovascular events versus control by 14% (p = 0.003), including MI by 21% (p = 0.01) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10501560/

Comparison of clinical outcomes of angiotensin receptor ... Real-world data demonstrate that ARBs might be associated with lower all-cause mortality and hospitalization for heart failure compared with ACEIs among ...

6. jacc.org jacc.org/doi/10.1016/j.jacc.2019.04.068

From ACE Inhibitors/ARBs to ARNIs in Coronary Artery ... At a median 21 months of follow-up, the primary outcome of CV death or HF hospitalization was reduced by eplerenone, with HR: 0.63 (95% CI: 0.54 to 0.74), as ...