EMERALD (Emergency Medicine Cardiovascular Risk Assessment for Lipid Disorders)
Phase: PHASE4
Conditions: Lipid Disorder
Sponsor: Wake Forest University Health Sciences

Protocol version: 
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EMERALD (Emergency Medicine Cardiovascular Risk Assessment for Lipid Disorders) 
 
 
IRB00091989 
 
 
NCT05742841 
 
 
07JUN2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol version: 
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Study Title: EMERALD (Emergency Medicine Cardiovascular Risk Assessment for 
Lipid Disorders 
 
Principal Investigator, Co-investigator(s):  Dr. Nicklaus Ashburn, Dr. Simon Mahler 
 
Sponsor or funding source: Atrium Health Wake Forest Baptist  
 
Background, Rationale and Context  
 
EMERALD (Emergency Medicine Cardiovascular Risk Assessment for Lipid Disorders) is a pilot 
study seeking to determine the feasibility of initiating medical therapy for hyperlipidemia (HLD) 
in the Emergency Department (ED) and will collect data essential to inform a future randomized 
controlled trial comparing ED HLD treatment to usual care (future NHLBI submission). HLD is a 
key cardiovascular disease (CVD) risk factor that is causally associated with atherosclerotic 
cardiovascular disease (ASCVD), the leading cause of US mortality and morbidity. 1–3 It is 
estimated that almost 40% of ED patients with chest pain have poorly managed or 
unrecognized HLD.4 However, patients are rarely screened for HLD in the ED and ED initiation 
medical therapy for HLD is exceedingly uncommon. Because HLD is rarely screened for, 
prescribing a statin is not the standard of care in the Emergency Department. Therefore, the 
current ED care paradigm, which does not address HLD, represents a missed opportunity to 
prevent ASCVD events. Every 38.7 mg/dL reduction in low-density lipoprotein-cholesterol (LDL-
C) is associated with a 21% decrease in ASCVD events and a 24% decrease in mortality. 5,6 
Thus, there is a clear opportunity to improve health for the millions of patients who present to 
the ED each year with undiagnosed and/or unmanaged HLD. 7,8 Diagnosing and managing a 
CVD risk factor such as HLD in the ED would be innovative and paradigm shifting. 
 
To address this gap in ASCVD prevention we have developed a novel ED-based HLD screening 
and treatment program: EMERALD (Emergency Medicine Cardiovascular Risk Assessment for 
Lipid Disorders). This program adapts HLD recommendations from the 2013 AHA/ACC and 
2022 US Preventive Services Task Force guidelines to the ED setting. The EMERALD 
intervention involves 1) ordering an ED lipid panel, 2) calculating 10-year ASCVD risk using the 
Pooled Cohort Equations9, 3) prescribing a moderate- or high-intensity statin if applicable, and 
4) referring patients to outpatient care (primary care, preventive cardiology, or general 
cardiology, depending on risk level). 10–12 Our preliminary data demonstrate that >90% of ED 
patients with acute chest pain believe the ED is an appropriate place to evaluate for HLD and 
>80% believe it is a reasonable place to start medical therapy for HLD. However, the feasibility 
of screening for HLD and initiating treatment in the ED setting is unclear.  It is unknown whether 
patients prescribed HLD treatment will fill these prescriptions, take their medication, and 
complete scheduled follow-ups. In addition, it is not clear whether busy Emergency Physicians 
will adopt and follow the steps of a preventative HLD care program. 
 
Objectives  
 
What is needed now is a pilot study examining if the ED can screen for HLD and estimate the 
anticipated effect size of EMERALD in lowering LDL-C. We propose a pilot study with 20 
patients designed to assess the feasibility of EMERALD and to explore changes in LDL-C by 
initiating medical therapy in the ED. The specific aims of this study are: 
 
Aim 1: Test the feasibility of EMERALD. We will determine the proportion of patients who 
receive a complete EMERALD assessment (ED lipid panel drawn, 10-year ASCVD risk 

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calculated with the Pooled Cohort Equations, and prescribed a statin), fill their prescription 
within 7-days of the ED encounter, and follow-up at 30-days for a repeat lipid panel. 
 
Aim 2: Explore changes in LDL-C after initiating preventive care with statin therapy in the 
ED. The primary outcome will be change in LDL-C at 30-days. The secondary outcome will be 
change at 30-days in non-high-density lipoprotein-cholesterol (non-HDL-C). 
 
Our experienced team is well-equipped to conduct this pilot study. This innovative proposal is a 
key step for determining if EMERALD is feasible and estimating its impact on LDL-C at 30-days. 
Our team consists of experts in emergency medicine, preventive cardiology, lipid disorders, and 
biostatistics. There is strong potential that the EMERALD concept could improve care for 
millions of ED patients across the US who have undiagnosed and/or unmanaged HLD. The 
concept could be expanded to other modifiable CVD risk factors, including diabetes, 
hypertension, obesity, and smoking. 
 
 
Methods: 
 
Overview and Design 
 
We propose a pilot study with 20 patients designed to assess the feasibility of EMERALD 
and to explore changes in LDL-C by initiating medical therapy in the ED. 
 
Subjects will be screened for Emerald in the Emergency Department. Research staff and 
investigators will screen for subjects in the Emergency Departments with the electric screening 
“track boards”. We will then screen patient health records and speak to their ED providers about 
EMERALD.  Labs will be ordered so that we can either rule in or out a patient for research.  
 
If they meet inclusion and no exclusion criteria, their treating Emergency Physician will be 
asked to initiate the EMERALD protocol, including: 1) ordering a lipid panel during the index 
ED encounter and 30-days after ED discharge, 2) completion of the Pooled Cohort 
Equations, and 3) starting medical therapy (moderate- or high-intensity statin, if appropriate) 
in the ED. 
 
The research will take place in the Emergency Department at Wake Forest Baptist Medical 
Center. Follow-ups will occur in the CTSI CRU space, Emergency Medicine CRU, or, if deemed 
appropriate, at an alternate site (e.g., subject's residence, local healthcare professional's site) 
for the 30 day follow-ups.  
     
 
Subjects selection criteria 
Treatments for Hyperlipidemia in ED settings: 
 
 
Inclusion Criteria 
• 
ED patients with chest pain 
• 
40-75 years old 
• 
An LDL-C ≥70 mg/dL on an ED lipid panel or have known diabetes or ASCVD 
• 
Negative standard of care pregnancy test or documented inability to bear children 
for female participants 
 

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Exclusion Criteria 
• 
Subject unwilling to take study medication 
• 
Pregnancy or breastfeeding 
• 
Inability to take study medication or, in the opinion of the Investigators/subject’s 
doctors unsuitable for study participation  
• 
ST-Segment Elevation Myocardial Infarction (STEMI) Activation 
• 
ST-Segment Depression >1 mm 
• 
On a Lipid Lowering Agent (Statin, PCSK9 Inhibitor, Bempedoic Acid, 
Ezetimibe, Inclisiran) 
• 
Unstable Vitals (BP <90, HR >120 or <50, O2 sat <90%) 
• 
Statin Intolerance 
• 
High-sensitivity Troponin I ≥100 ng/L 
• 
ESRD and/or GFR <30 mL/min/1.73 m2 
• 
Liver Cirrhosis 
• 
Hospitalization 
• 
Life Expectancy <1 Year 
• 
Transfer from Another Hospital 
• 
Prisoner 
• 
Non-English Speaking 
 
 
 
Intervention and Procedure  
 
This program adapts HLD recommendations from the 2013 AHA/ACC and 2022 US 
Preventive Services Task Force guidelines to the ED setting.  
 
To close this critical evidence gap, we propose a pilot study, which will test the feasibility of 
EMERALD and explore changes in LDL-C concentrations using 20 ED patients with chest 
pain who are 40-75 years old with an LDL-C ≥70 mg/dL on an ED lipid panel or have known 
diabetes or ASCVD. For patients enrolled, their treating Emergency Physician will be asked 
to initiate the EMERALD protocol, including: 1) ordering a lipid panel during the index ED 
encounter and 30-days (+/- 5 business days) after ED discharge, 2) completion of the 
Pooled Cohort Equations by the patient’s ED provider at the index visit, 3) starting medical 
therapy (moderate- or high-intensity statin/ rosuvastin) in the ED, if applicable, and 4) having 
subjects complete a drug diary documenting drug usage. This pilot will provide critical data 
regarding the feasibility of the EMERALD intervention and its estimated effect size on LDL-C 
concentration, which are needed to inform a future randomized trial (future NHLBI 
submission). Ignition funds will be used to pay for lipid measures, support statistical 
analysis, and provide patient compensation. This pilot project is essential for providing 
preliminary data for a future randomized controlled trial of EMERALD (future NHLBI 
submission). 
 
 
The EMERALD procedure involves  
1) Ordering an ED lipid panel 
2) The subject’s ED provider calculating the 10-year ASCVD risk using the Pooled 
Cohort Equations9 at the index visit, 
3) Based on the trial diagram, prescribing a moderate- or high-intensity statin (either 
rosuvastatin 10mg daily or rosuvastatin 40 mg daily) if applicable,  

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4) Have subjects complete a drug diary during the 30 days before their follow-up, and  
5) Bring subjects back 30-days (+/- 5 business days) after ED discharge to retest their 
Lipid Panel 
 
Outcome 
 
This pilot study will provide preliminary data regarding the feasibility of EMERALD and estimate 
its impact on LDL-C and non-HDL-C. We anticipate the pilot data will demonstrate that 
implementation of EMERALD is feasible in an ED setting (ED lipid panel drawn, 10-year ASCVD 
risk assessment performed, and statin therapy initiated) and will result in a trend towards 
reduced LDL-C among participants. 
 
 
Analytical Plan 
This pilot study will provide preliminary data regarding the feasibility of EMERALD and estimate 
its impact on LDL-C and non-HDL-C. We anticipate the pilot data will demonstrate that 
implementation of EMERALD is feasible in an ED setting (ED lipid panel drawn, 10-year ASCVD 
risk assessment performed, and statin therapy initiated) and will result in a trend towards 
reduced LDL-C among participants. These data will support a future NHLBI submission (likely 
K23 award for Dr. Nicklaus Ashburn with Dr. Mahler as mentor), which will use a randomized 
controlled trial design to examine the efficacy and patient adherence to EMERALD on a larger 
scale. If the pilot data are not supportive of the EMERALD concept, then the investigative team 
will reconsider the EMERALD program design before pursuing NIH funding. In either case, the 
data from this pilot will be essential for future proposals and used to produce the first publication 
regarding ED-initiated medical therapy for HLD. 
 
Human Subjects Protection 
 
General requirements: The study will be conducted in compliance to this study protocol, the 
current version of the Declaration of Helsinki, ICH GCP, and applicable local legal and 
regulatory requirements. 
 
Submission of study documents: Before study start, the study protocol, and subject information / 
informed consent and any other study-related document as required by applicable laws and 
regulations will be submitted to the Ethics Committee and regulatory authorities for written 
approval. Any protocol amendments or new or amended information that requires ethical 
consideration will be submitted for written approval, too. In addition, a study report (interim and 
/or full report) will be submitted to regulatory authorities in line with applicable timelines. 
 
Subject information and informed consent: Participation in this study will include a written 
informed consent, which will be collected in the ED. All subjects or legal representatives will be 
informed orally and in writing about the objectives of the study, its procedures, potential risks, 
and about the fact that to some extent data will be accessible for third parties - provided that 
data confidentiality is ensured at any time. The participation in this study will be entirely 
voluntary. Subjects will have the right to withdraw their willingness to participate in the trial at 
any time without affecting their future medical care in any way. Informed consent will be 
obtained from both the investigators and from the study coordinators  
 
Clinical study results and publication:  The results of the clinical study will be documented in a 
clinical study report and will be published (e.g. in a journal or presented in a scientific meeting). 
 

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Data confidentiality: Auditors, Ethics Committee, and the regulatory authorities will be granted 
direct access to the subject’s medical records to the extent permitted by the applicable law and 
regulation for verification of clinical study procedures, and/or data control, ensuring subject data 
confidentiality. The subject’s file and the source data will be archived in line with national and 
international legal requirements. 
 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of 
study participants.  The principal investigator will be assisted by other members of the study 
staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol 
changes will be promptly reported by the principal investigator or designated member of the 
research team to the IRB and sponsor or appropriate government agency if appropriate. 
 
 
 
References 
 
1.  Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic 
cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A 
consensus statement from the European Atherosclerosis Society Consensus Panel. Eur 
Heart J. 2017;38(32):2459-2472. 
2.  Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics-2021 Update: A 
Report From the American Heart Association. Circulation. 2021;143(8):e254-e743. 
3.  Vassy JL, Lu B, Ho YL, et al. Estimation of Atherosclerotic Cardiovascular Disease Risk 
Among Patients in the Veterans Affairs Health Care System. JAMA Netw Open. 
2020;3(7):e208236. 
4.  Blomkalns AL, O’Connell EM, Eady CE, Lindsell CJ, Gibler WB. Evaluation of dyslipidemia 
in the emergency department: impact of cholesterol testing on subsequent therapy. Am 
Heart J. 2006;152(6):1182-1186. 
5.  Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy 
and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 
170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. 
6.  Ross SD, Allen IE, Connelly JE, et al. Clinical outcomes in statin treatment trials: a meta-
analysis. Arch Intern Med. 1999;159(15):1793-1802. 
7.  Owens PL, Barrett ML, Gibson TB, Andrews RM, Weinick RM, Mutter RL. Emergency 
department care in the United States: a profile of national data sources. Ann Emerg Med. 
2010;56(2):150-165. 
8.  Hooker EA, Mallow PJ, Oglesby MM. Characteristics and Trends of Emergency 
Department Visits in the United States (2010-2014). J Emerg Med. 2019;56(3):344-351. 

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9.  Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment 
of cardiovascular risk: a report of the American College of Cardiology/American Heart 
Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S49-73. 
10.  Gulati Martha, Levy Phillip D., Mukherjee Debabrata, et al. 2021 
AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of 
Chest Pain. J Am Coll Cardiol. 2021;78(22):e187-e285. 
11.  Whelton Paul K., Carey Robert M., Aronow Wilbert S., et al. 2017 
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the 
Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J 
Am Coll Cardiol. 2018;71(19):e127-e248. 
12.  US Preventive Services Task Force, Mangione CM, Barry MJ, et al. Statin Use for the 
Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task 
Force Recommendation Statement. JAMA. 2022;328(8):746-753. 
 
Appendix 
1. Data collection form 
2. Copies of each questionnaires or surveys that will be used 
3. Consent form if one will be used 
4. Other Appendix items as appropriate