Statins + Lifestyle Counseling for High Cholesterol

(EMERALD RCT Trial)

Overseen By Lauren Koehler

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Statins, PCSK9 inhibitors

Disqualifiers: STEMI, ESRD, Liver cirrhosis, 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 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 30 days

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of statins (medications that lower cholesterol) and lifestyle counseling in reducing bad cholesterol levels in individuals at risk for heart problems. The study includes two groups: one receives usual care with general healthy living tips, while the other receives a personalized plan with statins and tailored advice based on their heart risk. Suitable candidates for this trial have visited the emergency room for heart-related symptoms, have known heart disease, or have been identified as high-risk for heart issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already on a lipid-lowering agent like statins or similar drugs.

What prior data suggests that this protocol is safe for patients with high cholesterol?

Research has shown that statins are generally safe and well-tolerated. Studies have found that these medications effectively lower "bad" LDL cholesterol levels with minimal issues. For most people, the risk of serious side effects, such as severe muscle injury or liver problems, remains very low. Specifically, the chance of muscle injury is less than 0.1%, and serious liver problems occur in about 0.001% of cases. Statins are often recommended to reduce the risk of heart attacks and strokes and have proven effective and safe for many patients, even those with existing heart conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a more personalized approach to managing high cholesterol, especially in emergency settings. Unlike standard care, which typically involves a primary care referral without immediate statin prescription from the Emergency Department, this trial stratifies patients based on their cardiovascular risk. This means patients with higher risks receive high-intensity statins and specialized referrals, potentially catching and managing severe cases more effectively. Additionally, the trial emphasizes integrating lifestyle counseling alongside medication, aiming for a holistic improvement in cholesterol management. By tailoring treatment intensity to individual risk levels, this approach could lead to more efficient and targeted outcomes for patients with high cholesterol.

What evidence suggests that this trial's treatments could be effective for high cholesterol?

Studies have shown that statins effectively lower "bad" LDL cholesterol and reduce heart-related problems. Statins also lower blood fats called triglycerides and can increase "good" HDL cholesterol. For people with heart disease, statins reduce the risk of heart attacks and strokes. In this trial, participants in the EMERALD arm will receive high-intensity statins, such as rosuvastatin, which work especially well for those with high LDL levels or known heart issues. Overall, statins have a strong track record of improving heart health and reducing cholesterol-related risks. ^{1 3 4 6 7}

Who Is on the Research Team?

Nick Ashburn

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for adults aged 40-75 who are being checked for heart issues in the ER and have a high risk of heart disease or existing conditions like diabetes or past heart events. It's not for those with severe ongoing heart attacks, on other cholesterol meds, with life expectancy under a year, unstable vitals, non-English speakers, pregnant women, prisoners, liver cirrhosis patients, statin intolerance or very poor kidney function.

Inclusion Criteria

Evaluation for Acute Coronary Syndrome

I am between 40 and 75 years old.

I have a high heart disease risk, diabetes, or a history of heart issues.

Exclusion Criteria

ST Depression >1 mm in Contiguous Leads

I have had a type of heart attack known as STEMI.

Anticipated Hospitalization or Placement into an Observation Protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a lipid panel test, statin prescription based on risk level, and healthy lifestyle counseling

30 days

1 visit (in-person)

Follow-up

Participants are monitored for changes in LDL-C and non-HDL-C levels and adherence to statin therapy

180 days

2 visits (in-person)

Qualitative Assessment

Qualitative interviews to determine facilitators and barriers to the EMERALD program

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Statin

Trial Overview

The EMERALD study tests if starting statins (rosuvastatin) and healthy lifestyle advice in the ER can lower bad cholesterol levels in at-risk patients not already getting this care. Patients will also get follow-up appointments to check progress and adherence.

How Is the Trial Designed?

Group I: Emergency Medicine Cardiovascular Risk Assessment for Lipid Disorders (EMERALD) arm Experimental Treatment 3 Interventions

In the EMERALD arm, care will vary by risk level: (1) patients with known atherosclerotic cardiovascular disease (ASCVD) will qualify for a high-intensity statin (rosuvastatin 40 mg daily) and referral to cardiology for secondary prevention, (2) patients with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL will receive a high-intensity statin and a cardiology referral for primary prevention, and (3) for the remaining patients, Emergency Department providers will calculate 10-year ASCVD risk using the Pooled Cohort Equations. These patients will be categorized as (3A) high risk patients (10-year risk ≥20%) who will receive a high-intensity statin and a cardiology referral and (3B) moderate risk patients (10-year risk ≥7.5% but \<20% or those with known diabetes and 10-year risk \<20%) who will receive a moderate-intensity statin (rosuvastatin 10 mg daily) and a primary care referral. EMERALD patients will also receive healthy lifestyle counseling.

Group II: Usual Care Arm Active Control 2 Interventions

Patients in the usual care arm will receive the current standard of care, which consists of primary care referral and no Emergency Department statin prescription. They will also receive healthy lifestyle counseling.

Statin is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Statins for:

• Hypercholesterolemia
• Hypertriglyceridemia
• Cardiovascular disease prevention

Approved in European Union as Statins for:

• Hypercholesterolemia
• Hypertriglyceridemia
• Cardiovascular disease prevention

Approved in Canada as Statins for:

• Hypercholesterolemia
• Hypertriglyceridemia
• Cardiovascular disease prevention

Approved in Japan as Statins for:

• Hypercholesterolemia
• Hypertriglyceridemia
• Cardiovascular disease prevention

Approved in China as Statins for:

• Hypercholesterolemia
• Hypertriglyceridemia
• Cardiovascular disease prevention

Approved in Switzerland as Statins for:

• Hypercholesterolemia
• Hypertriglyceridemia
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Statins, which inhibit HMG-CoA reductase, are effective in lowering cholesterol levels and are recommended for patients with primary hypercholesterolaemia or mixed hyperlipidaemia, regardless of existing atherosclerotic vascular disease.

These medications are generally well tolerated, with similar side effects such as gastrointestinal issues and muscle pain, highlighting the importance of understanding their pharmacokinetic properties for optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[HMG-CoA reductase inhibitors: a brief review of their pharmacological properties and clinical efficacy in cardiovascular disease]. da Silva, PM.[2013]

A meta-analysis of 52 clinical trials involving HMG-CoA reductase inhibitors (fluvastatin, lovastatin, pravastatin, and simvastatin) demonstrated that all four medications effectively lower cholesterol levels in patients with hypercholesterolemia.

Specific reductions in low-density lipoprotein cholesterol (LDL-C) and total cholesterol were significant, with simvastatin 40 mg/d showing the highest reduction of 40.7% in LDL-C, indicating strong efficacy across different dosages and agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in the treatment of patients with hypercholesterolemia: a meta-analysis of clinical trials. Kong, SX., Crawford, SY., Gandhi, SK., et al.[2019]

Statins have been proven effective in improving lipid levels and significantly reducing the risk of atherosclerotic coronary artery disease (CAD), which leads to lower morbidity and mortality rates associated with CAD.

While statins are generally well tolerated, there are safety concerns regarding potential adverse effects on muscles, liver, kidneys, and the nervous system, with some risks being well-documented and others remaining speculative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin safety: an overview and assessment of the data--2005. Bays, H.[2022]

A review of comparative studies involving over 25 patients per treatment group confirmed that lovastatin and pravastatin are approximately equally effective, while simvastatin is at least twice as effective per milligram compared to the other two.

All four HMG-CoA reductase inhibitors (lovastatin, pravastatin, simvastatin, and fluvastatin) have similar side-effect profiles, and recent trials do not support earlier claims of increased sleep disorders with lovastatin and simvastatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of clinical trials comparing HMG-CoA reductase inhibitors. Illingworth, DR., Tobert, JA.[2007]

Statins, particularly pravastatin and simvastatin, have been shown to significantly reduce coronary morbidity and mortality in both primary and secondary prevention of heart disease, even in patients with normal cholesterol levels.

The benefits of statins are evident across various demographics, including women, the elderly, and diabetics, indicating their broad efficacy regardless of baseline risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Planned, ongoing and recently completed clinical trials for atherosclerosis prevention and regression: an update. Mellies, M., McGovern, M.[2019]

Atorvastatin, evaluated in 21 completed and 23 ongoing clinical trials with a total of 4271 patients, demonstrated a favorable safety profile, with fewer than 2% of patients withdrawing due to adverse events.

The most common side effects were mild, including constipation and abdominal pain, and serious adverse events were rare, with only 0.7% of patients experiencing significant liver enzyme elevations, indicating atorvastatin is well-tolerated compared to other statins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the clinical safety profile of atorvastatin (lipitor), a new HMG-CoA reductase inhibitor. Black, DM., Bakker-Arkema, RG., Nawrocki, JW.[2019]

In a 24-week trial involving adults with high cholesterol, rosuvastatin significantly reduced LDL cholesterol levels more than atorvastatin, achieving a 60% reduction compared to 52% with atorvastatin at the highest doses.

Rosuvastatin also led to better overall lipid profile improvements, including total cholesterol and HDL cholesterol, indicating it may be a more effective option for patients at high risk for coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial. Schwartz, GG., Bolognese, MA., Tremblay, BP., et al.[2018]

In a study involving 84 patients treated with simvastatin (S), 42 with lovastatin (L), and 23 with pravastatin (P) over 6 months, simvastatin showed the most significant reduction in total cholesterol by 30.2%, indicating its strong efficacy in lowering cholesterol levels.

All three statins were generally well-tolerated, with no serious clinical abnormalities reported; however, simvastatin and lovastatin had higher incidences of mild side effects like headaches and muscle pain, suggesting a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of different HMG-CoA reductase inhibitors. Ditschuneit, HH., Kuhn, K., Ditschuneit, H.[2018]

Simvastatin is found to be twice as potent as lovastatin and pravastatin on a milligram-per-milligram basis, making it a strong option for lowering cholesterol levels.

Pravastatin is recommended as the preferred choice for patients requiring higher doses due to its lower incidence of myopathy, especially in posttransplant patients receiving cyclosporine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Hsu, I., Spinler, SA., Johnson, NE.[2018]

A review of 1,644,220 adverse event reports from 2004 to 2009 revealed that rosuvastatin is more strongly associated with muscular adverse events like myalgia and rhabdomyolysis compared to pravastatin and atorvastatin.

The analysis also found signals for acute renal failure associated with statin use, particularly with atorvastatin, although the association was weaker and no significant link was found for non-acute renal failure or increased blood creatinine levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system. Sakaeda, T., Kadoyama, K., Okuno, Y.[2021]

Citations

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Cholesterol Lowering Drugs - Endotext - NCBI Bookshelf

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Review Medications for Lipid Control: Statins vs Newer Drugs

Statins have proven efficacy and safety in reducing cardiovascular events and total mortality in patients with and without clinically evident ASCVD.

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ahajournals.org

ahajournals.org/doi/10.1161/circoutcomes.111.000071

Comparative Tolerability and Harms of Individual Statins

According to dose-level comparisons, individual statins resulted in higher odds of discontinuations with higher doses of atorvastatin and rosuvastatin.

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heart.org

heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications

Cholesterol Medications

Statins are most effective at lowering LDL (bad) cholesterol. They also help lower triglycerides (blood fats) and raise HDL (good) cholesterol.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10892755/

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According to the results of a meta-analysis, the decreases in significant coronary events [30,31], coronary revascularizations, and strokes were ...

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ahajournals.org

ahajournals.org/doi/10.1161/atv.0000000000000073

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The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%.

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(3) The manufacturer's prescribing information reported a low-density lipoprotein cholesterol reduction of 60% in patients receiving atorvastatin 80 mg daily.