Evolocumab for Coronary Heart Disease

(EMPOWER Trial)

Overseen By Leanne Barrett

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must be taking: PCSK-9 inhibitors

Must not be taking: PCSK-9 inhibitors

Disqualifiers: Myocardial infarction, Stroke, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 52 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how Evolocumab, a cholesterol-lowering medication, can improve blood flow in individuals with stable coronary artery disease, where the heart's blood vessels are narrowed. Researchers will image participants' hearts and blood vessels before and after 12 months of treatment to assess improvements. Eligible participants have stable coronary artery disease and high cholesterol levels not fully controlled by their current medication. A control group of similar patients will not receive the drug, allowing for comparison of results. The trial aims to provide new insights into managing heart disease with Evolocumab. As a Phase 4 trial, this research helps determine how this FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on a statin, you must be on a stable dose for at least 3 months before joining the study.

What is the safety track record for Evolocumab?

Research has shown that evolocumab is generally safe for people with heart disease. In a large study involving over 27,000 patients, evolocumab was well-tolerated for more than two years, with most patients not experiencing serious side effects.

Some individuals might experience mild reactions, such as cold symptoms or back pain, but these were uncommon and usually not severe. The FDA has approved evolocumab for lowering cholesterol in people who do not respond well to other treatments, indicating thorough safety testing.

Overall, evidence suggests that evolocumab is safe for most people, particularly those with heart issues. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about evolocumab for coronary heart disease because it targets a specific protein called PCSK9, which plays a role in regulating cholesterol levels. Unlike traditional treatments like statins, which reduce cholesterol by inhibiting its production in the liver, evolocumab works by helping the liver remove more LDL cholesterol from the blood. This unique mechanism of action offers a promising option for patients who may not respond well to statins or who need additional cholesterol-lowering beyond what statins can provide. Additionally, evolocumab is administered via injection, which can be advantageous for patients who struggle with daily oral medications.

What is the effectiveness track record for Evolocumab in treating coronary artery disease?

Research shows that Evolocumab lowers the risk of major heart problems, such as heart attacks and strokes. In this trial, some participants will receive Evolocumab, while others will be in a control group with no intervention. Studies have found that people taking Evolocumab experience fewer heart issues compared to those who do not. For instance, one study showed a 20% reduction in heart problems when Evolocumab was used with statins, a common cholesterol-lowering medication. This benefit appeared in just over two years and continued to improve over time. Overall, Evolocumab has proven effective in reducing the risk of serious heart events in people with heart disease. ^{1 5 6 7 8}

Who Is on the Research Team?

Diana Lopez, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 50 (men) or 55 (women) with stable coronary artery disease and LDL cholesterol ≥70 mg/dL. They must not be planning revascularization soon, have been on a steady statin dose for 3+ months if applicable, and meet certain criteria indicating heart issues. Excluded are pregnant/breastfeeding individuals, those with severe heart conditions, kidney failure, contraindications to vasodilators, recent major cardiac events or procedures, specific genetic disorders affecting cholesterol levels, severe heart failure or angina.

Inclusion Criteria

You have a high score indicating calcium buildup in your arteries.

Your nuclear perfusion imaging results are not normal.

You have widespread clogging of the arteries in three main areas of the body.

Exclusion Criteria

Your fasting triglyceride levels are higher than 500 mg/dL.

I have a serious heart valve problem.

Currently pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline rest/stress cardiac PET scan along with CCTA

1 week

1 visit (in-person)

Treatment

Participants receive PCSK-9 inhibition with Evolocumab for 12 months

52 weeks

Regular visits as per protocol

Follow-up

Participants undergo final PET scan and CCTA to assess changes in myocardial blood flow and plaque volume

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Evolocumab

Trial Overview

The study tests the effect of Evolocumab on blood flow in coronary arteries using PET scans and CCTA imaging before and after a year of treatment. It's an open-label pilot study where all participants receive the drug; there's also a control group without the drug to compare changes in myocardial blood flow and plaque volume.

How Is the Trial Designed?

Group I: Evolocumab Experimental Treatment 1 Intervention

Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the intervention.

Group II: Control Active Control 1 Intervention

Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the baseline.

Evolocumab is already approved in United States, European Union for the following indications:

Approved in United States as Repatha for:

• To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease
• Familial hypercholesterolemia
• High-risk patients with LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL on maximally tolerated statin therapy ± ezetimibe

Approved in European Union as Repatha for:

• Primary hypercholesterolaemia and mixed dyslipidaemia
• Homozygous familial hypercholesterolaemia

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Evolocumab is a monoclonal antibody that significantly reduces LDL cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia, showing treatment differences of 54.8% to 76.3% compared to placebo and 36.9% to 47.2% compared to ezetimibe over 12-week trials.

It is effective even in patients who are statin-intolerant or have homozygous familial hypercholesterolemia, maintaining its efficacy over the long term and demonstrating good tolerability, making it a valuable treatment option for those who struggle to achieve LDL-C goals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab: A Review in Hyperlipidemia. Keating, GM.[2019]

Evolocumab, a PCSK9 inhibitor, can significantly improve cardiovascular outcomes in high-risk patients, but its effectiveness can be compromised by improper injection techniques.

In a case study of a 41-year-old woman with familial hypercholesterolemia, her lack of response to the PCSK9 inhibitor was traced back to incorrect subcutaneous injection, emphasizing the need to ensure proper administration before considering genetic testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Small Change Can Make a Big Difference: A Lesson from Evolocumab. Mirzaee, S., Thein, PM., Wong, D., et al.[2021]

Evolocumab (Repatha(®)) is an effective injectable treatment for patients with familial hypercholesterolemia or statin intolerance, helping to significantly lower LDL cholesterol levels when statins alone are insufficient.

The review highlights the safety and efficacy of evolocumab based on results from various clinical trials, indicating its potential role as a second-line therapy after maximally tolerated statin therapy and lifestyle changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab. Dahagam, C., Goud, A., Abdelqader, A., et al.[2021]

Evolocumab (Repatha) is an FDA-approved PCSK9 inhibitor that can reduce LDL-cholesterol levels by approximately 60% in high-risk patients already on maximum statin therapy, showing similar efficacy and safety to another PCSK9 inhibitor, alirocumab (Praluent).

The long-term effects of evolocumab on cardiovascular outcomes and its overall safety profile are still not fully established, and both evolocumab and alirocumab are considered expensive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol. [2019]

Evolocumab (Repatha™) is an effective treatment for hypercholesterolaemia, approved in the EU and awaiting approval in the USA and Japan, that works by binding to PCSK9, enhancing the liver's ability to remove LDL-cholesterol from the blood.

The drug can be used alone or alongside statins and other lipid-lowering therapies, showing efficacy in both adults and adolescents with various forms of hypercholesterolaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab: First Global Approval. Markham, A.[2020]

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