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

Trial Summary

What is the purpose of this trial?

Emergency Medicine Cardiovascular Risk Assessment for Lipid Disorders (EMERALD) is a protocolized intervention based on American College of Cardiology/American Heart Association and US Preventive Services Task Force guidelines designed to initiate preventive cardiovascular care for emergency department patients being evaluated for acute coronary syndrome. The overarching goals of this proposal are to (1) determine the efficacy of EMERALD at lowering low-density lipoprotein cholesterol (LDL-C) and non high-density lipoprotein cholesterol (non-HDL-C) among at-risk Emergency Department (ED) patients who are not already receiving guideline-directed outpatient preventive care and (2) inform our understanding of patient adherence and determinants of implementation for ED-based cardiovascular disease prevention strategies.

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 data supports the effectiveness of the drug for high cholesterol?

Research shows that statins, including atorvastatin, simvastatin, pravastatin, and others, are effective in lowering LDL cholesterol levels, which can reduce the risk of heart disease. Studies have demonstrated that these drugs can significantly decrease cholesterol levels and improve heart health outcomes. ^{1 2 3 4 5}

Are statins safe for humans?

Statins, which include drugs like atorvastatin, simvastatin, and others, are generally well tolerated and have been used by millions of people. However, they can sometimes cause side effects like muscle pain, liver issues, and sleep disturbances. It's important to discuss any concerns with a healthcare provider. ^{1 2 6 7 8}

How is the drug Statins + Lifestyle Counseling unique for treating high cholesterol?

The combination of statins (cholesterol-lowering drugs) with lifestyle counseling is unique because it not only targets cholesterol levels through medication but also encourages healthy lifestyle changes, which can enhance the overall effectiveness of treatment and improve cardiovascular health. ^{1 3 5 9 10}

Research Team

Nick Ashburn

Principal Investigator

[e-mail]

Eligibility Criteria

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

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

ST Depression >1 mm in Contiguous Leads

Anticipated Hospitalization or Placement into an Observation Protocol

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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 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]

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]

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]

References

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

Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. [2018]

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

A review of clinical trials comparing HMG-CoA reductase inhibitors. [2007]

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

An overview of the clinical safety profile of atorvastatin (lipitor), a new HMG-CoA reductase inhibitor. [2019]

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Comparison of different HMG-CoA reductase inhibitors. [2018]

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

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

8. United States 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. [2021]

9. Portugal pubmed.ncbi.nlm.nih.gov

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

10. United States 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. [2018]