Randomized Controlled Trial of Alert-Based Computerized Decision Support for Optimizing Low-Density Lipoprotein Management (LDL-ALERT)

Randomized Controlled Trial of Alert-Based Computerized Decision Support for Optimizing Low-Density Lipoprotein Management (LDL-ALERT)

A 400-patient U.S.-based single-center Quality Improvement Initiative in the form of a randomized controlled trial focused on the feasibility of implementation of this electronic alert-based CDS (EPIC BPA) based on LDL-C values. The 400 patients will be comprised of 200 in the "Hospitalized Patient Cohort" and 200 in the "Outpatient Clinic Cohort." The allocation ratio will be 1:1 for an electronic alert-based CDS (EPIC BPA) notification versus no notification.

Study Overview

• Status: Active, not recruiting
• Conditions: ASCVD; Hyperlipemia, Mixed
• Intervention / Treatment: Behavioral: Alert

Detailed Description

Given the striking failure to achieve evidence-based and guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets and widespread underutilization of effective LDL-lowering therapies, including ezetimibe and PCSK9 inhibitors, even among highest risk patients, a heavy, unmitigated burden of cardiovascular risk persists, is addressable, and demands novel strategies. An alert-based computerized decision support (CDS) strategy addressed successfully a similar unmet need in cardiovascular medicine: the failure to prescribe antithrombotic therapy in atrial fibrillation patients at high-risk for stroke (Piazza G, et al. Eur Heart J. 2020 Mar 7;41(10):1086-1096). This alert-based CDS strategy tripled appropriate antithrombotic prescriptions in this vulnerable patient population. The alert reduced the odds of myocardial infarction (MI) at 90 days by 87% (OR 0.13; 95% CI 0.04-0.45) and cerebrovascular events or systemic embolism at 90 days by 88% (OR 0.12; 95% CI 0.0-0.91). Alert-based CDS effectively overcame barriers to guideline-directed therapy, integrating numerous clinical trials and evidence-based clinical practice guidelines, failure to identify at-risk patients, and educational gaps in strategies for stroke prevention.

The crisis in the failure to achieve guideline-directed LDL-C targets demonstrates similar clinical obstacles, suggesting that a CDS approach could be effective for optimizing lipid management. The following single-center, 400-patient, randomized controlled trial of an EPIC Best Practice Advisory (BPA; alert-based computerized decision support tool) aims to increase guideline-directed utilization of appropriate LDL-lowering therapies in undertreated inpatients and outpatients with atherosclerotic cardiovascular disease (ASCVD), including those with recent acute coronary syndrome (ACS). The study will evaluate this CDS intervention in both patient populations in parallel to gain insight into the impact of different settings on this approach and to better position implementation of this strategy in our own health systems and other clinical settings.

Study Design: A 400-patient U.S.-based single-center Quality Improvement Initiative in the form of a randomized controlled trial focused on the feasibility of implementation of this electronic alert-based CDS (EPIC BPA) based on LDL-C values. The 400 patients will be comprised of 200 in the "Hospitalized Patient Cohort" and 200 in the "Outpatient Clinic Cohort." The allocation ratio will be 1:1 for an electronic alert-based CDS (EPIC BPA) notification versus no notification.

Study Population: Patients eligible for enrollment will be drawn from two populations with atherosclerotic cardiovascular disease (ASCVD), including those with recent acute coronary syndrome (ACS): hospitalized patients (inpatients) and clinic patients (outpatients).

Inpatient Cohort: All patients ≥ 18 years old and admitted to the BWH Cardiovascular Medicine Service with a diagnosis (primary or secondary), medical history entry, or problem list entry of ASCVD (acute coronary syndromes, a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease) will be identified by the EPIC BPA. Those with a most recent (within 1 year) or current LDL-C value greater than 80 mg/dL (allowing for a 10% difference between goal LDL-C and current measurement) who are on a statin but not on ezetimibe and/or PCSK9 inhibitor will be potentially eligible for randomization. Any patients with no recent LDL-C measurement within the year prior to randomization will have an alert issued to their providers with recommendation for checking a lipid panel, which would be standard-of-care.

Outpatient Cohort: All patients ≥ 18 years old and seen in the BWH Watkins Cardiovascular Medicine Clinic with a diagnosis (primary of secondary) or problem list entry of ASCVD will be identified by the EPIC BPA. Those with a most recent (within 1 year) or current LDL-C value greater than 80 mg/dL (allowing for a 10% difference between goal LDL-C and current measurement) who are on a statin but not on ezetimibe and/or PCSK9 inhibitor will be potentially eligible for randomization. Any patients with no recent LDL-C measurement within one year will have an alert issued to their providers with recommendation for checking a lipid panel, which would be standard-of-care.

Intervention: The study team will devise a program to run within the EPIC Electronic Health Record (EHR) that will identify patients with ASCVD who are hospitalized on the BWH Cardiovascular Medicine Service or seen in the BWH Watkins Cardiovascular Medicine Clinic and have a most recent (within 1 year) or current LDL-C value greater than 80 mg/dL and are on a statin but not an PCSK9 inhibitor. In these patients who subsequently randomly assigned to the alert-based CDS strategy, an on-screen electronic alert will prompt the responsible inpatient provider (inpatient cohort) or the cardiologist of record for the clinic visit (outpatient cohort) as follows:

1. All patients whose LDL-C is not less than 70 mg/dL and not taking a maximally tolerated statin dose will prompt a recommendation for statin intensification
2. All patients whose LDL-C is within 20% of 70 mg/dL and who are on a maximally tolerated statin dose but not on ezetimibe or PCSK9 inhibitor will receive a prompt for adding ezetimibe
3. All patients whose LDL-C is greater than 20% of goal, and on a maximally tolerated statin (±ezetimibe) but not on PCSK9 inhibitor will receive a prompt for initiating PCSK9 inhibitor

The alert-based CDS will consist of an on-screen electronic dialogue box that will notify the clinician that the patient is at increased risk for cardiovascular events and is not at LDL-C goal according to current evidence-based clinical practice guidelines. The clinician will have the opportunity to proceed to an order template through which ezetimibe or a PCSK9 inhibitor can be prescribed. The clinician could also elect to learn more about current evidence-based clinical practice guideline recommendations for LDL targets. Finally, the clinician could elect to proceed without ordering more intensive lipid-lowering therapy or reading the guidelines but would have to provide a rationale for not prescribing ezetimibe or a PCSK9 inhibitor.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

• patients ≥ 18 years old AND
• admitted to the BWH Cardiovascular Medicine Service with a diagnosis (primary or secondary), medical history entry, or problem list entry of ASCVD (acute coronary syndromes, a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease) AND
• most recent (within 1 year) or current LDL-C value greater than 80 mg/dL AND
• on a statin but not on ezetimibe and/or PCSK9 inhibitor will be potentially eligible for randomization

Exclusion:

-already receiving PCSK9 inhibitor therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alert; an on-screen electronic alert will prompt the responsible inpatient provider (inpatient cohort) or the cardiologist of record for the clinic visit (outpatient cohort) as follows: All patients whose LDL-C is not less than 70 mg/dL and not taking a maximally tolerated statin dose will prompt a recommendation for statin intensification; All patients whose LDL-C is within 20% of 70 mg/dL and who are on a maximally tolerated statin dose but not on ezetimibe or PCSK9 inhibitor will receive a prompt for adding ezetimibe; All patients whose LDL-C is greater than 20% of goal, and on a maximally tolerated statin (±ezetimibe) but not on PCSK9 inhibitor will receive a prompt for initiating PCSK9 inhibitor	Behavioral: Alert; The alert-based CDS will consist of an on-screen electronic dialogue box that will notify the clinician that the patient is at increased risk for cardiovascular events and is not at LDL-C goal according to current evidence-based clinical practice guidelines. The clinician will have the opportunity to proceed to an order template through which ezetimibe or a PCSK9 inhibitor can be prescribed. The clinician could also elect to learn more about current evidence-based clinical practice guideline recommendations for LDL targets. Finally, the clinician could elect to proceed without ordering more intensive lipid-lowering therapy or reading the guidelines but would have to provide a rationale for not prescribing ezetimibe or a PCSK9 inhibitor.
No Intervention: No Alert; No notification will be issues

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of prescription of appropriate LDL-lowering therapy	frequency of prescription of appropriate LDL-lowering therapy, including statin intensification or addition of ezetimibe or PCSK9 inhibitors at 90 days in hospitalized and clinic patients with ASCVD, including recent ACS, and a most recent (within 1 year) or current LDL-C value greater than 80 mg/dL who are on a statin.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LDL-C level at next follow-up laboratory test	Change in LDL-C level at next follow-up laboratory test (at least three months after the identification of the qualifying LDL-C measurement) in hospitalized and clinic patients with ASCVD, including recent ACS, and a most recent (within 1 year) or current LDL value greater than 80 mg/dL who are on a statin.	90 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2021
• Primary Completion (Actual): December 30, 2022
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 10, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: cholesterol; hyperlipidemia; decision support; lipid-lowering
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypertriglyceridemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipidemias; Hyperlipoproteinemia Type V; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Xanthines; Caffeine
• Other Study ID Numbers: 2021P000749

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No